The Interdisciplinary Annotated Psychedelic Research Bibliography of 2024
Produced by Michael Haichin, PharmD
Each year, our Medical Advisor, Michael Haichin, PharmD (LinkedIn, Bluesky, Twitter), chalks up a list of the psychedelics articles he deems most important or intriguing. As his annual list exceeded five hundred publications in 2023, he came up with an idea that would a) have the list see the light of day; and, b) collate the opinions of other psychedelics researchers on last year’s papers.
As such, we are pleased to present the second annual Interdisciplinary Annotated Psychedelic Research Bibliography. Below, Michael presents his narrowed list of publications (around 500, down from over 2,000!), along with short comments from an interdisciplinary pool of researchers.
In what follows, Michael first introduces the Bibliography along with a few comments. We then provide an indicative summary of the types of comments received from researchers, before diving into the full annotated bibliography.
Reading this on a small screen? That might be tricky, as this is a very long webpage! You may wish to email this page to yourself so you can revisit it when you’re on a device with a larger screen: click here to do so.
Explore the 2024 Annotated Psychedelics Bibliography
Add a header to begin generating the table of contents
Introduction
Welcome to the second edition of the Interdisciplinary Annotated Psychedelic Research Bibliography!
For the past several years, with the help of the Psychedelic Alpha team, I have closely followed all the academic papers published about or related to psychedelics and compiled an annual list of the most intriguing ones.
Last year’s inaugural Annotated Bibliography was born from said list, with generous input from an invited interdisciplinary pool of academic authors and critics providing context and commentary to enrich our understanding of psychedelic research. Building on that foundation, this edition continues to explore the rapidly evolving research landscape and offers valuable perspectives from experts across the field.
In reflecting on the notable psychedelic moments of 2024, I found myself going back to Shayla Love’s 2022 Year in Review op-ed, which quoted Jack Kornfield, “After the Ecstasy, The Laundry”. The laundry symbolizes the challenges of integrating psychedelics into broader society and the maturation that must come with it.
It’s safe to say that last year was a challenging one for the field of psychedelics, where the metaphorical laundry certainly piled up. However, amidst these hurdles, the field has continued to grow, demonstrating resilience and a commitment to advancing our understanding of psychedelics. It is my hope that the 2024 edition of the bibliography captures the essence of this growth.
The number of psychedelic science publications flourished, and this project required narrowing a list of over 2,000 papers published online in 20241, to a more manageable ~500, before being sent to invited researchers. It was a true labour of love (and a test of my patience), but ultimately was a small fraction of the time spent considering and evolving the ideas that end up in these scientific publications that deserve engaging with.
The development of this list was far from scientific in process, in that I included what I found most interesting or what I thought might be most pertinent to the various disciplines in the field at Large (including the many I am less than qualified in). To further simplify the task, case reports, individual chapters or whole academic textbooks, and dissertations/theses were not included2.
This biased methodology undoubtedly resulted in the exclusion of very deserving papers, which I attempted to offset by asking participating researchers to nominate any excluded paper(s).
A few more notes about the list before moving on to the annotated bibliography:
- Let’s remember that this list is neither exhaustive nor definitive. Not all papers were read in full and thus their inclusion is not necessarily an endorsement.
- Similar to last year, despite some objection from certain invited researchers3, papers about MDMA, ketamine, and related entactogens and dissociatives were included under the “psychedelic” umbrella.
- The references are listed in alphabetical order and divided into the following categories: Reviews, Clinical Trials, Discovery & Preclinical, Editorials/Commentary, Miscellaneous, and Preprints.
I hope this is a valuable addition to researchers and anyone who doesn’t have time to read everything they’d like to (so, everybody), and inspires collaboration in hopes of folding some more laundry.
Lastly, thank you to those who commented on literature included in this year’s bibliography: Alex Kwan, Samuli Kangaslampi, Matteo Malgaroli, CJ Healy, Gretchen Shaub, Jacob Aday, Hailey Gilmore, Alaina Jaster, Rebecca Ehrenkranz, Lucie Berkovitch, Lauren Lepow, S. Parker Singleton, David Mathai, Sharday Mosurinjohn, Maia Malleways, Vince Polito, Matthew Baggott, Helena Aicher, Bente Vissel, Lauri Elsilä, Juliet Meccia, Chloé Pronovost-Morgan, Zoë Dubus, Eddie Jacobs, Meghan DellaCrosse, Gregory Yates, Harriet Phelan, Evan Lewis-Healey, Marc Duque Ramirez, and George Blackburne.
Are you a researcher interested in participating in the 2025 Annotated Bibliography? Please contact michael@psychedelicalpha.com.
A Brief Overview
While we received comments on a broad array of 2024’s publications, one of the papers that received the most attention was Aday et al.’s review, Psychedelic-assisted psychotherapy: Where is the psychotherapy research?”
Indeed, 2024 saw a continuation of the debate around the role of psychotherapy in psychedelic-based treatments, which was intensified by a 2023 publication from Compass Pathways Chief Medical Officer Guy Goodwin and co. that drew commentary in last year’s Bibliography. That 2023 article has since been responded to by a salvo from the likes of Alpert et al., Bogenschutz, Schenberg et al., O’Donnell et al., Earleywine et al., and the late Deckel et al., which attracted comments in this Bibliography, including from CJ Healy who described it as a “diverse series of thoughtful and often impassioned arguments against active efforts to minimize or excise entirely…the psychosocial component…of psychedelic therapy.” The question was also raised by Weintraub and Miklowitz, who asked: How should psychotherapy proceed when adjoined with psychedelics?
In her review of several psychotherapy-related articles, Gretchen Shaub suggests that some of the animosity around this topic is due to a lack of consensus terminology in the field. That, she says, “has resulted in the role of psychotherapy being an increasingly contentious issue for many stakeholders”.
Aday et al.’s review proposes ways in which we might make this debate more productive or empirical, such as through the publication of treatment manuals. Efforts to standardise the therapy element could benefit from mainstream psychotherapy research, the authors suggest, a view that Samuli Kangaslampi endorsed in his commentary on the article.
Others, including CJ Healy, appear to agree: “Psychedelic therapy is psychotherapy that involves the use of drugs, and so psychedelic therapy research ought to look methodologically and conceptually just as much like psychotherapy research as like drug research (if not more so!).”
On the topic of more practical suggestions for psychedelic researchers, Barnett et al.’s contribution in Psychopharmacology offers a blueprint for establishing psychedelic research programs, including a focus on “[u]nusual situations arising in psychedelic research”, which Jacob Aday said he found “highly interesting and underscores the wide spectrum of challenges one can expect to encounter in this field of research.”
Another publication that could have implications for the practice of psychedelic trials, and the interpretation of their findings, is Roseman et al.’s investigation of how “brief and relatively minor demands on attention during a psychedelic experience”, in the words of CJ Healy’s comments on the article, “prove to be significant enough distractions from subjective immersion in the experience that they compromise not only the acute phenomenological effects but also the long-term therapeutic benefits of the experience.”
Helena Aicher found the study “particularly noteworthy as it reinforces the long-standing understanding that contextual factors shape psychedelic experiences”, adding that “the findings also imply that results from prior studies involving acute assessments or experimental tasks during the psychedelic state may have been influenced by those very interventions.” She also warned that, in addition to differing doses and drugs, the design of studies should be considered when comparing effects across studies.
As might be clear already, many of those people researching psychedelics are well over the hype curve, instead increasingly focused on highlighting—and overcoming—challenges in psychedelic research and potential roll-out. Lauri Elsilä welcomes more critical perspectives, like Lemarchand et al.’s commentary in BMJ, but said that some of the issues identified in psychedelic studies should be addressed in clinical (psycho)pharmacological studies writ large.
The broad array of contributions, and commentary on said contributions submitted as part of this process, continues to impress. Here are just a handful of other topics discussed:
- McGovern et al.’s integrated theory of false insights and beliefs under psychedelics stirred discussion, with S. Parker Singleton describing it as “probably my favorite read of 2024”.
- Bartlett et al.’s review looked at queer representation in psychedelic research, while Bouchet et al. surveyed the inclusion (or lack thereof) of older adults in such work.
- Aepfelbacher et al.’s article on the role of awe and music in ketamine’s antidepressant effects made Maia Malleways wonder: “Could deliberately enhancing awe during ketamine sessions…enhance and prolong its therapeutic efficacy?” Greenway et al.’s study on music as an intervention to mitigate blood pressure increases on patients receiving IV ketamine for depression, meanwhile, interested University of Zurich researcher and psychotherapist Helena Aicher. She said that this is a line of research that might be worth extending to other psychoactive substances, like classical psychedelics or empathogens, which “could help understand the broader role of music and sensory environment for the physiological responses and subjective experiences across different pharmacological interventions.”
- Alex Kwan said that Braun et al.’s zebrafish behavioural assay “may be a promising approach for high throughput screens with live animals.” Lauri Elsilä, meanwhile, appreciated University of Bristol researchers’ efforts (Hinchcliffe et al.) in “developing rodent models that have better translational validity”.
- On the access side of the equation, McInnes et al.’s contribution explored ways of achieving insurance coverage for ketamine using real-world evidence. In reviewing the publication, Hailey Gilmore said that a “public benefit approach when pharma profit isn’t possible presents ripe conditions for transforming innovative treatment option access for the world’s 3rd leading cause of disability.”
- Breeksema et al.’s qualitative study of patient perspectives and experiences with psilocybin for treatment-resistant depression (TRD) was well-received when it was published last February. Here, Meghan DellaCrosse describes it as “a valuable contribution to the psychedelic literature as it centers on patient narratives”.
- Researchers at University Hospital Basel (Straumann et al.) published findings on the acute effects of MDMA and its two enantiomers in healthy subjects (N=24). In a detailed comment, Tactogen co-founder Matthew Baggott said it was a welcome addition to the literature, even if it does not initially replicate findings from mice studies in humans. Baggott also pointed out challenges in selecting comparable doses between the enantiomers, given a dearth of data. “Disappointingly”, he continued, “the enantiomers did not have dramatically different qualitative pharmacological profiles”, Baggott said, but added the “[p]roponents of the potential value of the R-enantiomer might point out that there were no measures that would be analogous to the improved fear extinction seen in mice”, referencing those preclinical studies. “[E]ven if the study proved disappointing for those of us hoping to improve on racemic MDMA, the study nonetheless provides a wealth of careful pharmacokinetics and dynamics information.”
- A paper by Myran et al. on emergency department visits involving hallucinogen use and risk of schizophrenia spectrum disorder caused quite the stir late last year. Here, Gregory Yates and Harriet Phelan describe it as “helpful for our work in the emergency department”, but suggest that the findings be taken “with a pinch of salt.” ‘Hallucinogens’ include PCP and amphetamines, they note (a matter they also noted in reviewing Simon et al.’s review of over fifty-four thousand medical cases), and they further suggest that there could be a ‘third variable’ at play. Lucie Berkovitch, meanwhile, described the findings as “alarming” and said that they “underscore the need for proactive follow-up and preventive strategies for this high-risk group.”
Reviews
Aday, J. S., Horton, D., Fernandes-Osterhold, G., O’Donovan, A., Bradley, E. R., Rosen, R. C., & Woolley, J. D. (2024). Psychedelic-assisted psychotherapy: Where is the psychotherapy research? Psychopharmacology, 241(8), 1517–1526. https://doi.org/10.1007/s00213-024-06620-x
“For a long time, research on psychedelic-assisted (psycho)therapy was strangely divorced from the more mainstream psychotherapy research that had been going on for decades. This meant that little attention was paid to things like the common factors of psychotherapy and transdiagnostic mechanisms of change previous research had uncovered, or to research designs best suited for comparing (elements) of psychotherapeutic approaches. In recent years, this has begun to change, but as Aday and colleagues write in this paper, “there is much the field has yet to leverage from decades of non-psychedelic psychotherapy research to optimize the psychotherapeutic aspect of treatment”. Here, the authors do a particularly good job of presenting a number of apt suggestions on what psychedelic-assisted psychotherapy could and should learn from mainstream psychotherapy research and how we should move forward to better understand and optimize the psychotherapy in psychedelic-assisted psychotherapy.” – Samuli Kangaslampi
“This critical review highlights a significant gap in psychedelic research: despite the term “psychedelic-assisted psychotherapy,” there has been remarkably little empirical investigation into the actual psychotherapy component. The authors identify how researchers have manipulated drug variables while neglecting to systematically study the accompanying psychological support, creating ambiguity about best practices. The authors correctly suggest to leverage established psychotherapy research methods — including standardizing protocols, identifying mechanisms of change, and using dismantling studies for advancing the field.” – Matteo Malgaroli
“Psychedelic therapy is psychotherapy that involves the use of drugs, and so psychedelic therapy research ought to look methodologically and conceptually just as much like psychotherapy research as like drug research (if not more so!).” – CJ Healy
“PAT, PAP, PT…there is yet to be consensus on language for psychedelic treatments in development. This lack of alignment has resulted in the role of psychotherapy being an increasingly contentious issue for many stakeholders. Valid arguments have been made regarding the role of psychotherapy in potentially FDA-approved psychedelic treatments. No one company, organization, or stakeholder group should be responsible for establishing best practices – a coordinated approach is required to support the entire industry. The opportunity is ripe for psychology to enter the chat. As experts continue to make valid and at times conflicting arguments, perhaps the conversation should evolve to identify who might “own” the psychotherapy of it all. There are highly qualified therapists with hundreds and thousands of hours of experience in psychedelic clinical trials confused about what their roles in real-world settings will be should products come to market. Isn’t everyone in this space confused about what their roles will be in the future? After all, this has never been done at commercial scale in the U.S. medical system. In an incipient and diverse industry might the current debate be missing the forest for the trees?
In December 2024 The American Psychiatric Association (APA) published updated practice guidelines on the treatment of Borderline Personality Disorder (BPD). The APA recommendation is tiered to include both psychosocial interventions and pharmacotherapy treatments. Importantly, they suggest that patients with BPD treated with “any psychotropic medication be time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.” Of note for emerging psychedelic treatments the APA does not distinguish between the numerous types of psychosocial interventions available; rather, the APA calls for a structured approach to psychotherapy, recognizing that many effective evidence-based options exist. Other examples of treatment models involving psychosocial interventions provide additional food for thought e.g. – SUD, HIV, bariatric surgery, dialysis, etc.
If the ultimate goal for those pursuing FDA approval is to provide treatment options that are safe and more effective than those presently available, shouldn’t the through line be meeting patients’ needs? Are we asking what patients want and incorporating that into decision-making or are we leaning into biased assumptions? All of the papers focused on this topic have provided space for healthy and much needed reflection and research.” – Gretchen Shaub (also responding to Weintraub et al. and Alpert et al., below.
Barnett, B. S., Vest, M. F., Delatte, M. S., King IV, F., Mauney, E. E., Coulson, A. J., Nayak, S. M., Hendricks, P. S., Greer, G. R., & Murnane, K. S. (2024). Practical considerations in the establishment of psychedelic research programs. Psychopharmacology, 242(1), 27–43. https://doi.org/10.1007/s00213-024-06722-6
“This paper is an incredibly useful blueprint for how to go about establishing a psychedelic research program. The section “Unusual situations arising in psychedelic research”, in particular, is a highly interesting read and underscores the wide spectrum of challenges one can expect to encounter in this field of research.” – Jacob Aday
This important manuscript advising investigators new to psychedelic trials is a comprehensive review (perhaps it should be added to the “Resources” section of any psychedelic company’s IIT program page). It highlights the longer timelines than expected due to additional regulation of scheduled substances over standard drug trials. From the outset, there is a need to begin building interdisciplinary relationships and support as soon as feasible, ranging from administration to community.
For most sites, there is a learning curve on conducting compliant FDA and DEA regulated research, given the pace of innovation in the mental health space over the last few decades. What’s more, psychedelic trials present unique challenges for trial design, managing selection/expectancy/evaluation biases, and also how to ethically conduct truly informed consent to ineffable experiences. Logistically, there are few clinical grade suppliers, and a duplicative system of state licensing for managing controlled substance inventory on site. Competent core staff are key, including in data management, recruitment, and laboratory processes – and yet, having such robust staffing expertise is challenging when funding for such work is limited.
Once more for the people in the back (of DOGE): funding remains the most substantial challenge in this space, and also the thing that would move the needle the most.” – Hailey Gilmore
Bartlett, A., Christ, C., Martins, B., Saxberg, K., & Ching, T. H. W. (2024). The library is open: A scoping review on queer representation in psychedelic research. Frontiers in Public Health, 12, 1472559. https://doi.org/10.3389/fpubh.2024.1472559
“Reviews like this are so important. Representation is so important. This review brought up a lot of good connections between psychedelics and queerness, specifically highlighting that psychedelic use has been a part of fluid conceptions of gender in several societies, and even the fungal kingdom of which psilocybin is a part of has thousands of distinct sexual identities. My favorite part of the review was about who is being studied in the psychedelic studies, and unfortunately out of the studies screened only five reported a breakdown of participants’ genders outside of the gender binary and no studies focused specifically on queer women. Another point this review makes that I appreciated was that many studies were excluded from their analysis due to historical pathologizing of psychedelic use within the queer community. I would love to see more work focused on the queer experience.” – Alaina Jaster
Bouchet, L., Sager, Z., Yrondi, A., Nigam, K. B., Anderson, B. T., Ross, S., Petridis, P. D., & Beaussant, Y. (2024). Older adults in psychedelic-assisted therapy trials: A systematic review. Journal of psychopharmacology (Oxford, England), 38(1), 33–48. https://doi.org/10.1177/02698811231215420
“This article points out the critical public health importance of including older adults in psychedelic clinical trials. The key impact of this paper is highlighting the dearth of representation of older adults in psychedelic trials – the authors find that less than 1.4% of participants in included psychedelic trials are age 65 or older. While there may be concerns about excess risk for experiencing adverse events in older populations, this paper did not find anything atypical for psychedelic studies (i.e., no serious adverse events were reported and both medical and psychiatric adverse events were transient). This study provides helpful insight into the potential risk-benefit profile of psychedelics in older adults, and includes initial recommendations for monitoring adverse events that may be more likely to occur in this population. These findings will hopefully pave the way for more inclusion of older adults in future psychedelic clinical trials.” – Rebecca Ehrenkranz
Calder, A. E., Hase, A., & Hasler, G. (2024). Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: A systematic review and meta-analysis. Molecular Psychiatry, 30(2), 763–776. https://doi.org/10.1038/s41380-024-02830-z
“Given the widely held theory that plasticity is behind the therapeutic effects of psychedelics and/or psychoplastogens, this systematic review and meta-analysis is quite interesting. One of the large issues within the field is the translational validity of animal studies to human studies, specifically as it relates to measures of plasticity. It’s extremely difficult to measure plasticity in humans and many people have been working on figuring out better measures, which include measuring the circulating levels of brain derived neurotrophic factor (BDNF) in blood. While this analysis of 29 studies found no changes in peripheral BDNF levels following psychoplastogen administration, it is a good first step in identifying gaps in the literature and what can be done to improve measures.” – Alaina Jaster
Glennon, R. A., & Dukat, M. (2024). 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents – A Review. ACS Pharmacology & Translational Science, 7(6), 1722–1745. https://doi.org/10.1021/acsptsci.4c00157
“I thought this review was pretty timely given the U.S. Drug Enforcement’s Agency’s attempt to schedule DOI and it’s DOx family member, DOC, this past year. Dr. Glennon is one of the foremost experts on psychedelic action at the serotonin 2A receptor, and one of the first to discover psychedelics activate the 2A receptor, making him the go-to guy on the subject. He provides a great overview of the chemistry, pharmacology and behavioral effects of DOI in this review. I believe it is a “must read” for anyone interested in psychedelic research.” – Alaina Jaster
Hinkle, J. T., Graziosi, M., Nayak, S. M., & Yaden, D. B. (2024). Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis. JAMA Psychiatry, 81(12), 1225. https://doi.org/10.1001/jamapsychiatry.2024.2546
“The occurrence of adverse events (AEs) in the medical use of psychedelics is a critical consideration for potential future marketing authorization. In this work, Hinkle et al. show that serious AEs are rare in clinical and research settings, although a systematic approach to AE assessment is lacking in many clinical trials. Overall, this study offers reassuring evidence about the safety profile of psychedelics when used in controlled environments.” – Lucie Berkovitch
Mathai, D. S. (2024). Learning how to make use of dissociative therapies. International Review of Psychiatry, 1–13. https://doi.org/10.1080/09540261.2024.2406329
“This article reframes dissociative therapies by highlighting their unique therapeutic potential, especially the often-overlooked role of subjective drug experiences like those with ketamine. It advances the field by calling for a more nuanced understanding of “dissociation,” distinguishing it from pathological constructs and highlighting its potential adaptive and meaning-making capacities, which could be intentionally harnessed in therapeutic contexts. The discussion opens new directions for integrating meaning-making and context into psychedelic and ketamine-assisted therapies.” – Lauren Lepow
McGovern, H. T., Grimmer, H. J., Doss, M. K., Hutchinson, B. T., Timmermann, C., Lyon, A., Corlett, P. R., & Laukkonen, R. E. (2024). An Integrated theory of false insights and beliefs under psychedelics. Communications Psychology, 2(1), 69. https://doi.org/10.1038/s44271-024-00120-6
“This was probably my favorite read of 2024. Psychedelics reliably produce the feeling of insight – that feeling (often strong) leads individuals to believe these insights are true. These insights (whether false or true) are to some degree a mechanism through which lasting behavioral and attitude changes occur following psychedelic administration (whether positive or negative). There tends to be a reverence around psychedelics leading to newcomers being told things like “trust the medicine”. With psychedelic use on the rise both in clinical and non-clinical settings, it feels extremely important to raise awareness around the possibility of false insights. McGovern et al provide a very readable review on this literature and some parameters through which insights can be evaluated post-acutely. This is a good one to send to your friends.” – S. Parker Singleton
Neitzke-Spruill, L., Devenot, N., Sisti, D., Averill, L. A., & McGuire, A. L. (2024). Bio-Psycho-Spiritual Perspectives on Psychedelics: Clinical and Ethical Implications. Perspectives in Biology and Medicine, 67(1), 117–142. https://doi.org/10.1353/pbm.2024.a919715
“Given the tremendous challenge of achieving a successful drug development program, psychedelic science is today at risk of losing its longstanding ties to psychological and historical perspectives. In this timely piece, Logan Neitze-Spruill and colleagues argue for the value of diverse frameworks when conceptualizing psychedelic effects and for avoiding the pitfalls of biomedical reductionism. The authors ultimately highlight that this critical work will require interdisciplinary training for researchers and interprofessional collaboration. Our field will be better off if we can make room for different ways of knowing, learning, and being.” – David Mathai
Sabé, M., Sulstarova, A., Glangetas, A., De Pieri, M., Mallet, L., Curtis, L., Richard-Lepouriel, H., Penzenstadler, L., Seragnoli, F., Thorens, G., Zullino, D., Preller, K., Böge, K., Leucht, S., Correll, C. U., Solmi, M., Kaiser, S., & Kirschner, M. (2024). Reconsidering evidence for psychedelic-induced psychosis: An overview of reviews, a systematic review, and meta-analysis of human studies. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02800-5
“Administering psychedelics to patients with schizophrenia intuitively seems at risk for triggering or exacerbating psychotic symptoms. However, empirical data on this topic is limited. Sabé et al. found that 3.8% of patients with schizophrenia experienced psychotic symptoms after psychedelic intake. By contrast, the incidence of psychedelic-induced psychosis in healthy controls and of prolonged psychosis was anecdotal. Psychedelic-induced psychotic disorders showed a high risk of converting to schizophrenia in 13.1% of the cases. These results call for a balanced risk-benefit assessment when considering psychedelics for patients with depression and co-occurring schizophrenia or psychotic history.” – Lucie Berkovitch
Schmid, Y., & Bershad, A. K. (2024). Altered States and Social Bonds: Effects of MDMA and Serotonergic Psychedelics on Social Behavior as a Mechanism Underlying Substance-Assisted Therapy. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(5), 490–499. https://doi.org/10.1016/j.bpsc.2024.02.001
“An implication of the findings discussed in this review is that the effects of psychedelics on self-processing/self-experience, emotional processing/emotional experience, and social processing/social experience are closely related and likely fundamentally inseparable both conceptually and mechanistically.” – CJ Healy
Shinozuka, K., Jerotic, K., Mediano, P., Zhao, A. T., Preller, K. H., Carhart-Harris, R., & Kringelbach, M. L. (2024). Synergistic, multi-level understanding of psychedelics: Three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology. Translational Psychiatry, 14(1), 485. https://doi.org/10.1038/s41398-024-03187-1
“Shinozuka et al present an impressive dissertation on psychedelic literature, extensively covering their effects on pharmacology, neuroimaging, and phenomenology. They provide extensive coverage on a broad spectrum of literature. Additionally, they perform 3 meta-analyses – using creative approaches in the case of neuroimaging, which has been a notoriously difficult literature to synthesize in psychedelics. Lastly, they relate the results of each level (pharma, imaging, experience) to neural fingerprints (relation to 7 a priori resting-state networks) in an effort to uniquely unify these three levels of understanding. A truly massive effort.” – S. Parker Singleton
Solaja, I., Haldane, K., Mason, N., Weiss, B., Xu, X., Xu, M., Nikolin, S., Jayasena, T., Millard, M., Brett, J., Bayes, A., Loo, C. K., & Martin, D. M. (2024). Who are you after psychedelics? A systematic review and a meta-analysis of the magnitude of long-term effects of serotonergic psychedelics on cognition/creativity, emotional processing and personality. Neuroscience & Biobehavioral Reviews, 158, 105570. https://doi.org/10.1016/j.neubiorev.2024.105570
“Much has been made of how psychedelic experiences can change a person, especially of potential changes in personality (sometimes erroneously claimed to be fully stable in adulthood otherwise). Here, Ivana Solaja and colleagues looked systematically at the evidence up to July 2022 for long-term (minimum one week) changes in cognition/creativity, emotional processing, and personality after serotonergic psychedelics. Mostly the review shows that there is little evidence from controlled studies for such changes and that, as always, more research is needed. The only significant effects that did emerge were for faster reaction times for disgust and sadness, interestingly. While it sometimes feels the ratio of reviews to empirical research papers is unreasonably high in psychedelic research, careful systematic reviews like this are important to temper dramatic claims about things like changes in personality. Clearly, some individual people experience radical changes after taking a psychedelic, but for now at least, there is no solid evidence to suggest that on average they change people’s personality or enhance their creativity.” – Samuli Kangaslampi
Yaden, D. B., Goldy, S. P., Weiss, B., & Griffiths, R. R. (2024). Clinically relevant acute subjective effects of psychedelics beyond mystical experience. Nature Reviews Psychology, 3(9), 606–621. https://doi.org/10.1038/s44159-024-00345-6
“This paper rehearses the past psychedelic mysticism story in order to attempt to go beyond it to other experiences people may have with psychedelics that can either help or hinder their healing and growth. In this story we can see the kernel of how psychedelic science research has mismatched some of its methods to its questions, which Yaden et al. go some way toward acknowledging when they caution researchers that quantitative approaches neglect to probe crucial components of construct validity. They advocate qualitative, iterative and evidence-based approaches to item development that use meta-surveys and interviews to probe sources of construct-irrelevant variance. Yet, what this call should prompt researchers to do, above all, is zoom out to conduct a rigorous self-inquiry into why they desire to find out in the first place, and for what purpose, using these methods. The science of psychedelic subjective experience that Yaden et al. track here and elsewhere begins with William James, who distilled his discussion of mystical experience from richly detailed cases of how such experiences functioned in particular lives, through specific practices (ritual technologies, social frameworks of traditions, etc.), oriented toward specific spiritual purposes articulated through and iteratively informing an anthropology, a metaphysics, and an ontology. Walter Stace then explicitly shed this detail in order to provide the phenomenological typology of mysticism as the basis of the comparison – mysticism becomes a state devoid of any enabling constraints (tradition, context) or purpose guiding practice. The MEQ then formulated by Walter Pahnke was motivated by trying to show a certain effect happened, rather than understand the skills people were using to work with the experience, for what purposes, and how they formulated those purposes in relation to a lifeway and a worldview. By operationalizing mysticism as an artificial grade bar, the MEQ pushed the study of psychedelics’ acute subjective effects deeply into the abstract. Pahnke’s dissertation reported that “three or four of the ten psilocybin subjects reached the 60% to 70% level of completeness,” neglecting to explain what it is to have a “partial” mystical experience, or what the purpose of such an experience is for the subjects’ pastoral or theological practice. The methodological wager that a survey method would yield epistemological precision by virtue of being amenable to quantitative analysis, has continued to shape studies whose methods similarly obscure what happened in the experiment and limit how it could be interpreted. In rightly pointing out that psychedelic science has often neglected to incorporate insights from psychological science that has already long studied processes such as emotions or self-identity, Yaden et al.’s paper also raises the issue that in these literatures, too, states are often likewise studied so abstractly as to produce tautological discussions. The science of awe, which they highlight as particularly relevant to acute psychedelic experience, is a good example here, with studies often designed to show participants visuals that they predict will elicit awe, and then finding neural or other physiological markers that are interpreted to be consonant with the phenomenological elements that the experimenters and or subjects associate with awe. Additionally, the research on meditation, conceived of as simultaneously a state and an active process, should be instructive here in the push to enhance methodological rigour on acute psychedelic subjective experience. The meditation research has made clear that a state, such as “mystical” or “awe” guarantees nothing – in fact, there is no state separable from the skills one has to be in that state and the role of a practice path around those skills and those states throughout a lifecourse. The therapeutic course after a psychedelic experience – whether and how someone’s wellbeing increases or decreases over time – involves a conative process of using skills to model their phenomenological, emotional, cognitive, etc. experiences, their interrelationships, and the relationship of their subjectivity to everything they exist in relation to. As an acute subjective experience, awe or other supposedly beneficial psychedelic experiences may be conducive to having the motivation and fortitude not to dissociate, and therefore to be integrated enough to do this modelling. The greatest analytical traction will come as the mixed-methods research Yaden et al. call for begins zooming out to account in its study conceptualization and design for the diachronic, contextual, and practical reality in which phenomenological moments have their meaning.” – Sharday Mosurinjohn
The above publications received comments from the researchers we surveyed. Here are further 2024 publications that Michael included in his list.
***
Anna, O., Michael, A., Apostolakis, M., Mammadov, E., Mitka, A., Kalatta, M. A., Koumas, M., Georgiou, A., Chatzittofis, A., Panayiotou, G., Gergiou, P., Zarate, C. A., & Zanos, P. (2024). Ketamine and hydroxynorketamine as novel pharmacotherapies for the treatment of Opioid-Use Disorders. Biological psychiatry, S0006-3223(24)01591-9. Advance online publication. https://doi.org/10.1016/j.biopsych.2024.09.008
Allen, J., Dames, S. S., Foldi, C. J., & Shultz, S. R. (2024). Psychedelics for acquired brain injury: A review of molecular mechanisms and therapeutic potential. Molecular Psychiatry, 29(3), 671–685. https://doi.org/10.1038/s41380-023-02360-0
Asch, R. H., Abdallah, C. G., Carson, R. E., & Esterlis, I. (2024). Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression. Neuropsychopharmacology, 50(1), 153–163. https://doi.org/10.1038/s41386-024-01913-3
Askey, T., Lasrado, R., Maiarú, M., & Stephens, G. J. (2024). Psilocybin as a novel treatment for chronic pain. British Journal of Pharmacology, bph.17420. https://doi.org/10.1111/bph.17420
Atiq, M. A., Baker, M. R., Voort, J. L. V., Vargas, M. V., & Choi, D.-S. (2024). Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties. Psychopharmacology. https://doi.org/10.1007/s00213-024-06599-5
Barstowe, A., & Kajonius, P. J. (2024). Masking Influences: A Systematic Review of Placebo Control and Masking in Psychedelic Studies. Journal of Psychoactive Drugs, 1–11. https://doi.org/10.1080/02791072.2024.2424272
Basedow, L. A., Majić, T., Hafiz, N. J., Algharably, E. A. E., Kreutz, R., & Riemer, T. G. (2024). Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA – a systematic review and meta-analysis. Scientific Reports, 14(1), 14782. https://doi.org/10.1038/s41598-024-65391-9
Campanale, A., Inserra, A., & Comai, S. (2024). Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 134, 111058. https://doi.org/10.1016/j.pnpbp.2024.111058
Chiamulera, C., Benvegnù, G., Piva, A., & Paolone, G. (2024). Ecocebo: How the interaction between environment and drug effects may improve pharmacotherapy outcomes. Neuroscience & Biobehavioral Reviews, 161, 105648. https://doi.org/10.1016/j.neubiorev.2024.105648
Colcott, J., Guerin, A. A., Carter, O., Meikle, S., & Bedi, G. (2024). Side-effects of mdma-assisted psychotherapy: A systematic review and meta-analysis. Neuropsychopharmacology, 49(8), 1208–1226. https://doi.org/10.1038/s41386-024-01865-8
Downey, A. E., Bradley, E. R., Lerche, A. S., O’Donovan, A., Krystal, A. D., & Woolley, J. (2024). A Plea for Nuance: Should People with a Family History of Bipolar Disorder Be Excluded from Clinical Trials of Psilocybin Therapy? Psychedelic Medicine, 2(2), 61–73. https://doi.org/10.1089/psymed.2023.0051
Downey, A. E., Chaphekar, A. V., Woolley, J., & Raymond-Flesch, M. (2024). Psilocybin therapy and anorexia nervosa: A narrative review of safety considerations for researchers and clinicians. Journal of Eating Disorders, 12(1), 49. https://doi.org/10.1186/s40337-024-01005-z
Efthimiou, A. A., Cardinale, A. M., & Kepa, A. (2024). The Role of Music in Psychedelic-Assisted Therapy: A Comparative Analysis of Neuroscientific Research, Indigenous Entheogenic Ritual, and Contemporary Care Models. Psychedelic Medicine, 2(4), 221–233. https://doi.org/10.1089/psymed.2023.0058
Enkavi, G., Girych, M., Moliner, R., Vattulainen, I., & Castrén, E. (2024). TrkB transmembrane domain: Bridging structural understanding with therapeutic strategy. Trends in Biochemical Sciences, 49(5), 445–456. https://doi.org/10.1016/j.tibs.2024.02.001
Erritzoe, D., Timmermann, C., Godfrey, K., Castro-Rodrigues, P., Peill, J., Carhart-Harris, R. L., Nutt, D. J., & Wall, M. B. (2024). Exploring mechanisms of psychedelic action using neuroimaging. Nature Mental Health, 2(2), 141–153. https://doi.org/10.1038/s44220-023-00172-3
E-Wen McCulloch, D., Liechti, M. E., Kuypers, K. Pc., Nutt, D., Lundberg, J., Stenbæk, D. S., Goodwin, G. M., Gründer, G., Butlen-Ducuing, F., Haberkamp, M., Thirstrup, S., & Knudsen, G. M. (2024). Knowledge gaps in psychedelic medicalisation: Clinical studies and regulatory aspects. Neuroscience Applied, 3, 103938. https://doi.org/10.1016/j.nsa.2024.103938
Fordyce, B. A., & Roth, B. L. (2024). Making Sense of Psychedelics in the CNS. International Journal of Neuropsychopharmacology, 27(2), pyae007. https://doi.org/10.1093/ijnp/pyae007
Freidel, N., Kreuder, L., Rabinovitch, B. S., Chen, F. Y., Huang, R. S. T., & Lewis, E. C. (2024). Psychedelics, epilepsy, and seizures: A review. Frontiers in Pharmacology, 14, 1326815. https://doi.org/10.3389/fphar.2023.1326815
Ghaznavi, S., Ruskin, J. N., Haggerty, S. J., King, F., & Rosenbaum, J. F. (2024). Primum Non Nocere: The Onus to Characterize the Potential Harms of Psychedelic Treatment. American Journal of Psychiatry, 182(1), 47–53. https://doi.org/10.1176/appi.ajp.20230914
Gobbi, G. (2024). The psychopharmacology of psychedelics: Where the brain meets spirituality (CCNP Innovations in Neuropsychopharmacology Award). Journal of Psychiatry and Neuroscience, 49(5), E301–E318. https://doi.org/10.1503/jpn.240037
Goldy, S. P., Hendricks, P. S., Keltner, D., & Yaden, D. B. (2024). Considering distinct positive emotions in psychedelic science. International Review of Psychiatry, 1–12. https://doi.org/10.1080/09540261.2024.2394221
Halman, A., Conyers, R., Moore, C., Khatri, D., Sarris, J., & Perkins, D. (2024). Harnessing Pharmacogenomics in Clinical Research on Psychedelic‐Assisted Therapy. Clinical Pharmacology & Therapeutics, 117(1), 106–115. https://doi.org/10.1002/cpt.3459
Haniff, Z. R., Bocharova, M., Mantingh, T., Rucker, J. J., Velayudhan, L., Taylor, D. M., Young, A. H., Aarsland, D., Vernon, A. C., & Thuret, S. (2024). Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases. Pharmacology & Therapeutics, 258, 108641. https://doi.org/10.1016/j.pharmthera.2024.108641
Hatzipantelis, C. J., & Olson, D. E. (2024). The Effects of Psychedelics on Neuronal Physiology. Annual Review of Physiology, 86(1), 27–47. https://doi.org/10.1146/annurev-physiol-042022-020923
Higa, G. S. V., Viana, F. J. C., Francis-Oliveira, J., Cruvinel, E., Franchin, T. S., Marcourakis, T., Ulrich, H., & De Pasquale, R. (2024). Serotonergic neuromodulation of synaptic plasticity. Neuropharmacology, 257, 110036. https://doi.org/10.1016/j.neuropharm.2024.110036
Holze, F., Singh, N., Liechti, M. E., & D’Souza, D. C. (2024). Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(5), 472–489. https://doi.org/10.1016/j.bpsc.2024.01.007
Hsu, T.-W., Tsai, C.-K., Kao, Y.-C., Thompson, T., Carvalho, A. F., Yang, F.-C., Tseng, P.-T., Hsu, C.-W., Yu, C.-L., Tu, Y.-K., & Liang, C.-S. (2024). Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: Systematic review and Bayesian network meta-analysis. BMJ, e078607. https://doi.org/10.1136/bmj-2023-078607
Hughes, M. E., & Garcia-Romeu, A. (2024). Ethnoracial inclusion in clinical trials of psychedelics: A systematic review. eClinicalMedicine, 74, 102711. https://doi.org/10.1016/j.eclinm.2024.102711
Humphreys, K., Todd Korthuis, P., Stjepanović, D., & Hall, W. (2024). Therapeutic Potential of Psychedelic Drugs: Navigating High Hopes, Strong Claims, Weak Evidence, and Big Money. Annual Review of Psychology, 76(1), 143–165. https://doi.org/10.1146/annurev-psych-020124-023532
Inserra, A., Campanale, A., Rezai, T., Romualdi, P., & Rubino, T. (2024). Epigenetic mechanisms of rapid-acting antidepressants. Translational Psychiatry, 14(1), 359. https://doi.org/10.1038/s41398-024-03055-y
Jevotovsky, D. S., Chopra, H., Pak, D. J., Durbhakula, S., Shustorovich, A., Juneja, T., Broachwala, M. Y., AlFarra, T., Silver, C., Kreitzer, G., Oreoluwa, P., Weissman, B. B., AlFarra, A., Mayrsohn, B. G., Orhurhu, V., Emerick, T., Furnish, T., & Castellanos, J. P. (2024). Psilocybin and chronic neuropathic pain: A systematic review. Regional Anesthesia & Pain Medicine, rapm-2024-105532. https://doi.org/10.1136/rapm-2024-105532
Kheirkhah, M., Nugent, A. C., Livinski, A. A., Neely, L., Johnson, S. C., Henter, I. D., Varnosfaderani, S. D., Price, R. B., Hejazi, N., Yavi, M., Jamalabadi, H., Javaheripour, N., Walter, M., & Zarate, C. A. (2024). Exploring the impact of music on response to ketamine/esketamine: A scoping review. Neuroscience & Biobehavioral Reviews, 162, 105693. https://doi.org/10.1016/j.neubiorev.2024.105693
Leone, L., McSpadden, B., DeMarco, A., Enten, L., Kline, R., & Fonzo, G. A. (2024). Psychedelics and Evidence-based Psychotherapy: A Systematic Review with Recommendations for Advancing Psychedelic Therapy Research. The Psychiatric clinics of North America, 47(2), 367–398. https://doi.org/10.1016/j.psc.2024.02.006
Lewis, E. C., Jaeger, A., Girn, M., Omene, E., Brendle, M., & Argento, E. (2024). Exploring psychedelic-assisted therapy in the treatment of functional seizures: A review of underlying mechanisms and associated brain networks. Journal of Psychopharmacology, 38(5), 407–416. https://doi.org/10.1177/02698811241248395
Lewis, V., Rurak, G., Salmaso, N., & Aguilar-Valles, A. (2024). An integrative view on the cell-type-specific mechanisms of ketamine’s antidepressant actions. Trends in Neurosciences, 47(3), 195–208. https://doi.org/10.1016/j.tins.2023.12.004
Li, J.-R., Chiang, K.-T., Kao, Y.-C., Yu, C.-L., Yang, F.-C., Liang, C.-S., & Hsu, T.-W. (2024). The association between study design and antidepressant effects in psychedelic-assisted therapy: A meta-analysis. Journal of Affective Disorders, 369, 421–428. https://doi.org/10.1016/j.jad.2024.10.016
Liao, C., Dua, A. N., Wojtasiewicz, C., Liston, C., & Kwan, A. C. (2024). Structural neural plasticity evoked by rapid-acting antidepressant interventions. Nature Reviews Neuroscience, 26(2), 101–114. https://doi.org/10.1038/s41583-024-00876-0
Low, Z. X. B., Ng, W. S., Lim, E. S. Y., Goh, B. H., & Kumari, Y. (2024). The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 136, 111139. https://doi.org/10.1016/j.pnpbp.2024.111139
Luoma, J., Allen, L. R., Gold, V., & Stauffer, C. (2024). Getting in Touch with Touch: The Importance of Studying Touch in MDMA-Assisted Therapy and the Development of a New Self-Report Measure. Psychedelic Medicine, 2:1, 25-32. https://doi.org/10.1089/psymed.2023.0033
Madsen, C. A., Navarro, M. L., Elfving, B., Kessing, L. V., Castrén, E., Mikkelsen, J. D., & Knudsen, G. M. (2024). The effect of antidepressant treatment on blood BDNF levels in depressed patients: A review and methodological recommendations for assessment of BDNF in blood. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 87, 35–55. https://doi.org/10.1016/j.euroneuro.2024.06.008
Meshkat, S., Tello‐Gerez, T. J., Gholaminezhad, F., Dunkley, B. T., Reichelt, A. C., Erritzoe, D., Vermetten, E., Zhang, Y., Greenshaw, A., Burback, L., Winkler, O., Jetly, R., Mayo, L. M., & Bhat, V. (2024). Impact of psilocybin on cognitive function: A systematic review. Psychiatry and Clinical Neurosciences, 78(12), 744–764. https://doi.org/10.1111/pcn.13741
Mohammad Aghaei, A., Weleff, J., Martins, B., Ing, K., Fontenele, R., Barnett, B. S., Anand, A., & Bassir Nia, A. (2024). Psychotherapeutic Interventions in Clinical Trials of Psychedelics for the Treatment of Alcohol Use Disorder. Current Addiction Reports, 11(4), 685–712. https://doi.org/10.1007/s40429-024-00574-y
Murphy, R. J., Muthukumaraswamy, S., & De Wit, H. (2024). Microdosing Psychedelics: Current Evidence From Controlled Studies. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(5), 500–511. https://doi.org/10.1016/j.bpsc.2024.01.002
Neumann, J., Dhein, S., Kirchhefer, U., Hofmann, B., & Gergs, U. (2024). Effects of hallucinogenic drugs on the human heart. Frontiers in Pharmacology, 15, 1334218. https://doi.org/10.3389/fphar.2024.1334218
Page, C. E., Epperson, C. N., Novick, A. M., Duffy, K. A., & Thompson, S. M. (2024). Beyond the serotonin deficit hypothesis: Communicating a neuroplasticity framework of major depressive disorder. Molecular Psychiatry, 29(12), 3802–3813. https://doi.org/10.1038/s41380-024-02625-2
Palitsky, R., Canby, N. K., Van Dam, N. T., Levin-Aspenson, H. F., Kaplan, D. M., Maples-Keller, J., Raison, C. L., Grant, G. H., Dunlop, B. W., & Britton, W. B. (2024). Leveraging meditation research for the study of psychedelic-related adverse effects. International Review of Psychiatry, 1–15. https://doi.org/10.1080/09540261.2024.2420745
Peck, S. K., Fisher, H., Kim, J., Shao, S., Trim, J., & Kaye, W. H. (2024). Psychedelic treatment for anorexia nervosa: A first-hand view of how psilocybin treatment did and did not help. Psychedelics, 1–4. https://doi.org/10.61373/pp024e.0034
Perez Rosal, S. R., La Torre, J. T., Birnkammer, S., Chernoloz, O., Williams, M. T., & Faber, S. C. (2024). Expert recommendations for Germany’s integration of psychedelic-assisted therapy. BMC Medical Education, 24(1), 1202. https://doi.org/10.1186/s12909-024-06141-3
Polito, V., & Liknaitzky, P. (2024). Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research. Journal of Psychopharmacology, 38(8), 701–711. https://doi.org/10.1177/02698811241254831
Ramaekers, J. G., Reckweg, J. T., & Mason, N. L. (2024). Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression. American Journal of Psychiatry, 182(1), 33–46. https://doi.org/10.1176/appi.ajp.20230890
Reid, M. J., Kettner, H., Blanken, T. F., Weiss, B., & Carhartt-Harris, R. (2024). Preliminary Evidence of Sleep Improvements Following Psilocybin Administration, and their Involvement in Antidepressant Therapeutic Action. Current Psychiatry Reports, 26(11), 659–669. https://doi.org/10.1007/s11920-024-01539-8
Rouaud, A., Calder, A. E., & Hasler, G. (2024). Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins. Journal of Psychopharmacology, 38(3), 217–224. https://doi.org/10.1177/02698811231225609
Salerno, J. A., & Rehen, S. (2024). Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro. iScience, 27(5), 109631. https://doi.org/10.1016/j.isci.2024.109631
Sapienza, J., Martini, F., Comai, S., Cavallaro, R., Spangaro, M., De Gregorio, D., & Bosia, M. (2024). Psychedelics and schizophrenia: A double-edged sword. Molecular Psychiatry, 30(2), 679–692. https://doi.org/10.1038/s41380-024-02743-x
Schipper, S., Nigam, K., Schmid, Y., Piechotta, V., Ljuslin, M., Beaussant, Y., Schwarzer, G., & Boehlke, C. (2024). Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database of Systematic Reviews, 2024(9). https://doi.org/10.1002/14651858.CD015383.pub2
Seybert, C., Schimmers, N., Silva, L., Breeksema, J. J., Veraart, J., Bessa, B. S., d’Orsi, D., Schoevers, R. A., & Oliveira-Maia, A. J. (2024). Quality of reporting on psychological interventions in psychedelic treatments: A systematic review. The Lancet Psychiatry, 12(1), 54–66. https://doi.org/10.1016/S2215-0366(24)00333-X
Singh, B., Kung, S., & Vande Voort, J. L. (2024). Intravenous (IV) ketamine versus intranasal esketamine for depression– Advantage IV ketamine? Journal of Affective Disorders, 356, 564–567. https://doi.org/10.1016/j.jad.2024.04.088
Soto-Angona, Ó., Fortea, A., Fortea, L., Martínez-Ramírez, M., Santamarina, E., López, F. J. G., Knudsen, G. M., & Ona, G. (2024). Do classic psychedelics increase the risk of seizures? A scoping review. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 85, 35–42. https://doi.org/10.1016/j.euroneuro.2024.05.002
Swieczkowski, D., Kwaśny, A., Pruc, M., Gaca, Z., Szarpak, Prof. L., & Cubała, Prof. W. J. (2024). Efficacy and Safety of Psilocybin in the Treatment of Major Depressive Disorder (MDD): A Dose-Response Network Meta-Analysis of Randomized Placebo-Controlled Clinical Trials. Psychiatry Research, 116337. https://doi.org/10.1016/j.psychres.2024.116337
Szigeti, B., & Heifets, B. D. (2024). Expectancy Effects in Psychedelic Trials. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(5), 512–521. https://doi.org/10.1016/j.bpsc.2024.02.004
Tavares, V. D. D. O., Da Costa Gonçalves, K. T., De Morais Barros, M. L., De Brito, A. J. C., Cavalcanti-Ribeiro, P., Palhano-Fontes, F., Falchi-Carvalho, M., Nunes, E. A., Sarris, J., Perkins, D., Fernandes-Osterhold, G., De Araujo, D. B., & Galvão-Coelho, N. L. (2024). Ketamine’s Altered States Meta-Analysis: The Relationship Between Psychomimetic and Clinical Effects With Focus in Depression. Journal of Clinical Psychopharmacology. https://doi.org/10.1097/JCP.0000000000001946
Tipado, Z., Kuypers, K. P. C., Sorger, B., & Ramaekers, J. G. (2024). Visual hallucinations originating in the retinofugal pathway under clinical and psychedelic conditions. European Neuropsychopharmacology, 85, 10–20. https://doi.org/10.1016/j.euroneuro.2024.04.011
Torrado Pacheco, A., & Moghaddam, B. (2024). Licit use of illicit drugs for treating depression: The pill and the process. Journal of Clinical Investigation, 134(12), e180217. https://doi.org/10.1172/JCI180217
Werle, I., & Bertoglio, L. J. (2024). Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents. Neuroscience & Biobehavioral Reviews, 167, 105899. https://doi.org/10.1016/j.neubiorev.2024.105899
White, E., Kennedy, T., Ruffell, S., Perkins, D., & Sarris, J. (2024). Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review. International Journal of Toxicology, 43(3), 327–339. https://doi.org/10.1177/10915818241230916
Wong, S., Kwan, A. T. H., Teopiz, K. M., Le, G. H., Meshkat, S., Ho, R., d’Andrea, G., Cao, B., Di Vincenzo, J. D., Rosenblat, J. D., & McIntyre, R. S. (2024). A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review. Journal of Affective Disorders, 350, 698–705. https://doi.org/10.1016/j.jad.2024.01.142
Yildirim, B., Sahin, S. S., Gee, A., Jauhar, S., Rucker, J., Salgado-Pineda, P., Pomarol-Clotet, E., & McKenna, P. (2024). Adverse psychiatric effects of psychedelic drugs: A systematic review of case reports. Psychological Medicine, 54(15), 4035–4047. https://doi.org/10.1017/S0033291724002496
Clinical Trials
Aaronson, S. T., Van Der Vaart, A., Miller, T., LaPratt, J., Swartz, K., Shoultz, A., Lauterbach, M., Suppes, T., & Sackeim, H. A. (2024). Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial. American Journal of Psychiatry, 182(1), 104–113. https://doi.org/10.1176/appi.ajp.20231063
“In this study, Aaronson et al. investigated the safety and efficacy of psilocybin in patients with severe and comorbid treatment-resistant depression. They evidence positive efficacy and safety results sustained at 12 weeks. Despite the small sample size and open-label design, these findings lay important groundwork for future research and care, as these patients are typically the most challenging to treat in real-life clinical practice.” – Lucie Berkovitch
Aepfelbacher, J., Panny, B., & Price, R. B. (2024). Experiences of Awe Mediate Ketamine’s Antidepressant Effects: Findings From a Randomized Controlled Trial in Treatment-Resistant Depression. Biological Psychiatry Global Open Science, 4(4), 100316. https://doi.org/10.1016/j.bpsgos.2024.100316
“Unlike classic psychedelics, the role of ketamine’s acute subjective experiences in its therapeutic efficacy remains underexplored. This randomized, placebo-controlled trial advances the field by specifically examining the role of awe. Results show that experiences of awe during a single ketamine infusion, rather than dissociation, statistically mediated reductions in depression. Remarkably, these mediation effects persisted up to 30 days post-infusion, suggesting that stronger experiences of awe may allow for more sustained antidepressant effects. Could deliberately enhancing awe during ketamine sessions – through guided reflection, imagery, or music – enhance and prolong its therapeutic efficacy? Further research is warranted to better understand ketamine-induced awe and its underlying mechanisms.” – Maia Malleways
Allen, N., Jeremiah, A., Murphy, R., Sumner, R., Forsyth, A., Hoeh, N., Menkes, D. B., Evans, W., Muthukumaraswamy, S., Sundram, F., & Roop, P. (2024). LSD increases sleep duration the night after microdosing. Translational Psychiatry, 14(1), 191. https://doi.org/10.1038/s41398-024-02900-4
“This paper reports that participants in a 10ug LSD microdosing condition slept about 20 minutes longer the night after microdosing, compared to people in the control condition. I found this to be a very intriguing demonstration of a clinically meaningful microdosing outcome that is unlikely to be due to placebo. There’s virtually no scientific data on the effectiveness of different microdosing schedules but the delayed effect reported here supports the idea that it may be important to space out dosing days.” – Vince Polito
Atila, C., Straumann, I., Vizeli, P., Beck, J., Monnerat, S., Holze, F., Liechti, M. E., & Christ-Crain, M. (2024). Oxytocin and the Role of Fluid Restriction in MDMA-Induced Hyponatremia: A Secondary Analysis of 4 Randomized Clinical Trials. JAMA Network Open, 7(11), e2445278. https://doi.org/10.1001/jamanetworkopen.2024.45278
“Acute hyponatremia (low sodium in the blood) is an apparently dose-independent adverse effect of MDMA that, when symptomatic, is associated with high risk of morbidity or even mortality. MDMA-related hyponatremia can be particularly bedeviling because it has nonspecific symptoms, including headache, nausea, and lethargy, that may be naively (and dangerously) interpreted as evidence of dehydration. Early studies suggested MDMA-related hyponatremia might be caused by drug-induced release of the antidiuretic hormone vasopressin, possibly in combination with excessive fluid consumption. Subsequent studies administering MDMA to healthy participants supported a role for fluid consumption but did not find evidence that vasopressin was contributing to MDMA-related hyponatremia. The current manuscript conducted a pooled analysis of four MDMA administration studies with healthy participants and found that mild MDMA-related hyponatremia was common despite the clinical setting. Moreover, hyponatremia was associated with plasma oxytocin rather than vasopressin. This suggests oxytocin may be cross-binding to receptors for the structurally similar vasopressin. Given that oxytocin is theorized to contribute to the therapeutic effects of MDMA, hyponatremia may be an inherent risk with MDMA. Happily, this risk appears to be manageable as no cases of hyponatremia occurred in a subset of 15 participants in a protocol with restricted fluid intake. All in all, this paper provides more evidence that both experimental and therapeutic use of MDMA should acutely limit intake of solute free fluids.” – Matthew Baggott
Back, A. L., Freeman-Young, T. K., Morgan, L., Sethi, T., Baker, K. K., Myers, S., McGregor, B. A., Harvey, K., Tai, M., Kollefrath, A., Thomas, B. J., Sorta, D., Kaelen, M., Kelmendi, B., & Gooley, T. A. (2024). Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial. JAMA Network Open, 7(12), e2449026. https://doi.org/10.1001/jamanetworkopen.2024.49026
“This was a really interesting clinical trial in a targeted patient population. My favorite thing about it though is the reporting on the methods and results is absolutely top-tier and fully transparent. I hope this sets a standard for trials going forward as having access to results in many forms is key to our ability to robustly synthesize evidence across the field.” – S. Parker Singleton
Deco, G., Sanz Perl, Y., Johnson, S., Bourke, N., Carhart-Harris, R. L., & Kringelbach, M. L. (2024). Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression. Nature Mental Health, 2(9), 1096–1110. https://doi.org/10.1038/s44220-024-00298-y
“This study by Deco et al. delves into the brain mechanisms underlying antidepressant effects of psilocybin and escitalopram. They confirmed that both substances significantly changed hierarchical brain organization, but, interestingly, in opposite directions. Moreover, the patterns of reconfiguration varied between responders and non-responders, within and across treatment groups. Overall, these results illustrate how different antidepressants rebalance pathological brain dynamics in depression and offers a valuable framework for understanding individualized responses to treatment.” – Lucie Berkovitch
Glue, P., Loo, C., Fam, J., Lane, H.-Y., Young, A. H., Surman, P., BEDROC study investigators, Glozier, N., Fitzgerald, P., Liu, D., Sharma, S., Grunfeld, J., Barton, D., Hopwood, M., Miles, W., Williams, M., Carson, S., Fam, J., Tor, P.-C., … Huang, Y.-J. (2024). Extended-release ketamine tablets for treatment-resistant depression: A randomized placebo-controlled phase 2 trial. Nature Medicine, 30(7), 2004–2009. https://doi.org/10.1038/s41591-024-03063-x
“In this interesting study, Glue et al., evaluated the efficacy and the safety of an oral extended-release form of ketamine (R-107) in treatment-resistant depression. Following an open-labeled enrichment phase consisting in administering 120 mg of R-107 daily, responders were randomized to receive double-blind doses (30-180 mg) or a placebo for 12 weeks. A sustained dose-dependent response was observed, particularly in the 180 mg group, with a favorable safety profile. These results position extended-release oral ketamine as a promising alternative to existing intranasal and intravenous formulations.” – Lucie Berkovitch
Greenway, K. T., Garel, N., Dinh-Williams, L.-A. L., Beaulieu, S., Turecki, G., Rej, S., & Richard-Devantoy, S. (2024). Music as an Intervention to Improve the Hemodynamic Response of Ketamine in Depression: A Randomized Clinical Trial. JAMA Network Open, 7(2), e2354719. https://doi.org/10.1001/jamanetworkopen.2023.54719
“This randomized clinical trial by Greenway and colleagues investigates whether music can mitigate ketamine-induced hemodynamic changes in patients receiving intravenous ketamine for treatment-resistant depression. The authors highlight that ketamine’s stimulatory effects on blood pressure can require pharmacological intervention in a significant subset of patients. They tested whether curated music during ketamine infusions could reduce these effects, finding that music significantly attenuated increases in systolic blood pressure but had no effect on diastolic pressure. The study underscores how environmental factors, such as auditory stimuli, might modulate ketamine’s physiological and psychoactive effects. While the trial is limited by its modest sample size (N=32), the results suggest music as a nonpharmacological adjunct to improve the safety profile of ketamine therapy. The authors call for future research with larger samples to confirm these findings and explore the broader clinical implications of integrating music into ketamine therapy.
What remains unaddressed, however, is whether different styles of music might elicit differential effects on ketamine-induced hemodynamic responses. Given prior research demonstrating that musical elements (rhythm, tempo, mode, genre, consonant vs dissonant, lyrics, etc.) can influence physiological and psychological parameters (blood pressure, heart rate, respiration, mood, arousal, etc.) (see for example Koelsch & Jäncke, 2015), it is plausible that these factors could also play a role when combined with pharmacological interventions.
A deeper investigation into the nuances of musical selection could offer valuable insights into how auditory stimuli may optimize safety and therapeutic efficacy of ketamine-assisted treatments. Additionally, extending this line of research to other psychoactive substances (e.g., classical psychedelics or empathogens) could help understand the broader role of music and sensory environment for the physiological responses and subjective experiences across different pharmacological interventions.” – Helena Aicher
Haggarty, C., Molla, H., Glazer, J., Tare, I., Rains, A., De Wit, H., & Lee, R. (2024). Low-Dose LSD Alters Early and Late Event-Related Potentials to Emotional Faces. Psychedelic Medicine, 2(4), 210–220. https://doi.org/10.1089/psymed.2024.0005
“I found this paper to be quite interesting due to its use of EEG to understand emotional processing in the brain. So many studies with psychedelics are specifically focused on using these substances as a treatment for mood-based disorders, and even more recently there has been an interest in subthreshold doses of psychedelics to improve mood in healthy people. Despite the heightened interest in psychedelics’ prosocial effects at low doses, a lot is unknown about how different doses of psychedelics directly alter emotional processing. The authors found that low dose LSD reduced amplitude of event-related potential (ERP) elicited in the part of the brain responsible for visuospatial processing in response to neutral faces, but not angry or happy faces. Further, they found that LSD reduced the amplitude of ERPs elicited in brain regions responsible for emotional processing and decision-making in response to neutral and happy faces, but not angry faces. This study provides key insights into how different brain regions are involved in LSD’s differential effects on social and emotional information processing, suggesting that LSD dampens emotional responses in general and isn’t necessarily “prosocial” as many hypothesize.” – Alaina Jaster
Jungwirth, J., Von Rotz, R., Dziobek, I., Vollenweider, F. X., & Preller, K. H. (2024). Psilocybin increases emotional empathy in patients with major depression. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02875-0
“A variety of acute and post-acute subjective effects of psychedelics (e.g., mystical experience, positive affect) have been repeatedly investigated – but this study addresses a less-explored component of social relationships and therapeutic processes that may be affected by psychedelics: empathy. This study was a randomized, double blind, placebo-controlled trial of 51 participants with depression. Key findings are that psilocybin is associated with emotional empathy, but not implicit or cognitive empathy, and that there were no correlations between increased empathy and reduced depression symptoms. Given the strong theoretical basis for the study and role of empathy in healthy social relationships, it was perhaps unexpected to find that psilocybin only had lasting effects on emotional empathy and that empathy does not seem to be a mechanism through which psilocybin may improve depression. The authors appropriately note limitations of the study (e.g., relatively short follow up period, expectancy bias) and provide interesting preliminary evidence that would support future work on the effects of psilocybin on empathy.” – Rebecca Ehrenkranz
Levin, A. W., Lancelotta, R., Sepeda, N. D., Gukasyan, N., Nayak, S., Wagener, T. L., Barrett, F. S., Griffiths, R. R., & Davis, A. K. (2024). The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder. PLOS ONE, 19(3), e0300501. https://doi.org/10.1371/journal.pone.0300501
“Psychotherapy is a social situation, and the findings of this study reinforce that the fact that therapists are people with whom patients are in relationship and not nameless professionals performing impersonal interventions is not just relevant to our understanding of mechanisms of therapeutic action but in fact of critical and central consequence.” – CJ Healy
Maples-Keller, J. L., Hyatt, C. S., Phillips, N. L., Sharpe, B. M., Sherrill, A., Yasinski, C., Reiff, C., Rakofsky, J., Rauch, S. A. M., Dunlop, B. W., & Rothbaum, B. O. (2024). Rapid Effects of MDMA Administration on Self-Reported Personality Traits and Affect State: A Randomized, Placebo-Controlled Trial in Healthy Adults. Journal of Psychoactive Drugs, 1–9. https://doi.org/10.1080/02791072.2024.2420044
“Illicit use of MDMA has been associated with both improved mood (“afterglow”) and lowered mood (“midweek lows”) in the days after use. In contrast, MDMA administration in controlled settings has been mainly associated with modest sub-acute side effects such as difficulty concentrating (22% of 166 study participants in Vizeli and Liechti 2017) and lack of energy (30%). This study finds evidence supporting an afterglow-like condition at 48 hours after 100 mg MDMA (or placebo) was administered to healthy MDMA-experienced participants. This was detected with both an instrument designed to measure self-reported personality (IPIP-NEO-60, which detected a medium effect-size increase in Openness) and another designed to measure affect (PANAS-X, which saw a smaller effect-size increase in Positive Affect). Because participants were MDMA-experienced, it’s a little unclear how prevalent this afterglow experience might be among the general population or specific patient populations. Nonetheless, the study provides evidence that MDMA can subacutely improve mood outside of therapeutic contexts. MDMA is not normally considered a fast acting antidepressant. Still, it has been reported to potently increase neuroplasticity in the same assays that shows effects for ketamine and other fast acting antidepressants. If antidepressant-like mood effects are measurable in the days after drug exposure, perhaps MDMA and other entactogens can also produce an enhanced capacity for change and growth in the same time window? If so, it would seem important to study how this can be made reliable and used to support therapeutic outcomes.” – Matthew Baggott
Mehtani, N. J., Johnson, M. O., Hendricks, P. S., Mitchell, J., & Anderson, B. T. (2024). Psilocybin-assisted therapy and HIV-related shame. Scientific Reports, 14(1), 17919. https://doi.org/10.1038/s41598-024-68908-4
“This study suggests the tremendous potential for psilocybin-assisted therapy to reduce shame in people with HIV who may struggle with significant barriers to wellbeing. More broadly, this research considers the value of moving beyond psychiatric diagnosis and conventional symptom reduction as targets for psychedelic interventions and further considering targets like psychological functioning and self-identity as key health-related outcomes. One notable finding from this trial was that, while most people benefited, sexual abuse-related shame increased in two participants after psilocybin – suggesting that psychedelic therapy may not always be straightforward, and that careful support might be needed in vulnerable populations.” – David Mathai
Mortaheb, S., Fort, L. D., Mason, N. L., Mallaroni, P., Ramaekers, J. G., & Demertzi, A. (2024). Dynamic Functional Hyperconnectivity After Psilocybin Intake Is Primarily Associated With Oceanic Boundlessness. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(7), 681–692. https://doi.org/10.1016/j.bpsc.2024.04.001
“Mortaheb et al. reanalyzed resting-state fMRI data from 49 healthy individuals who received either psilocybin or placebo. They used sliding-window dynamic functional connectivity to track the temporal evolution of discrete connectivity states. Psilocybin led to widespread increases in static functional connectivity, alongside a heightened occurrence of a recurrent hyperconnected pattern which correlated with subjective experience. Notably, this pattern was linked to low BOLD signal amplitude, which has been associated with heightened cortical arousal and increased vigilance. Global BOLD signal remains a debated topic in psychedelic neuroimaging, as its treatment (preserving vs. regressing) can influence findings. Indeed, when Mortaheb et al. applied global signal regression, the hyperconnected pattern disappeared, leading them to advocate for preserving global signal in dynamic analyses. This aligns with their previous work on mind blanking, which also identified a hyperconnected state—though one marked by increased signal amplitude.” – S. Parker Singleton
Murphy, R. J., Sumner, R. L., Godfrey, K., Mabidikama, A., Roberts, R. P., Sundram, F., & Muthukumaraswamy, S. (2024). Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide. Psychopharmacology, 242(2), 337–351. https://doi.org/10.1007/s00213-024-06680-z
“Murphy et al. conducted a rigorous and exhaustive evaluation of the impact of LSD microdosing on creativity. They uncover a striking contrast: participants subjectively reported feeling more creative on dose days, yet objective creativity measures showed no significant difference compared to placebo. These results add to growing evidence that microdosing’s perceived benefits may stem from subjective experience rather than measurable cognitive enhancements.” – Lucie Berkovitch
Nicholas, C. R., Banks, M. I., Lennertz, R. C., Wenthur, C. J., Krause, B. M., Riedner, B. A., Smith, R. F., Hutson, P. R., Sauder, C. J., Dunne, J. D., Roseman, L., & Raison, C. L. (2024). Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience. Translational Psychiatry, 14(1), 372. https://doi.org/10.1038/s41398-024-03059-8
“A creative approach to understand how recollection and quality of the psychedelic experience relates to outcomes.” – S. Parker Singleton
Raja, S. M., Guptill, J. T., Mack, M., Peterson, M., Byard, S., Twieg, R., Jordan, L., Rich, N., Castledine, R., Bourne, S., Wilmshurst, M., Oxendine, S., Avula, S. G. C., Zuleta, H., Quigley, P., Lawson, S., McQuaker, S. J., Ahmadkhaniha, R., Appelbaum, L. G., … Thomas, C. J. (2024). A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2 R ,6 R )‐Hydroxynorketamine in Healthy Volunteers. Clinical Pharmacology & Therapeutics, 116(5), 1314–1324. https://doi.org/10.1002/cpt.3391
“I liked this paper because one of the first psychedelic research experiences I had was giving hydroxynorketamine (HNK) to cortical neurons in a dish during my undergraduate research course. It’s really great to see this line of research still being explored. This phase 1 assessment, while an obvious important step into developing HNK as a pharmacotherapy, is a great example of the amount of work and effort that goes into the understanding of the safety and tolerability of a drug. Ketamine has been shown to have positive outcomes for people with depression but not without some risks of dependence. It would be amazing to develop HNK as an alternative for those at risk of developing a substance use disorder that still are suffering from depression, and this study is a great first step in that direction.” – Alaina Jaster
Roseman, L., Erritzoe, D., Nutt, D., Carhart-Harris, R., & Timmermann, C. (2024). Interrupting the Psychedelic Experience Through Contextual Manipulation to Study Experience Efficacy. JAMA Network Open, 7(7), e2422181. https://doi.org/10.1001/jamanetworkopen.2024.22181
“This brilliant little paper reports the finding that brief and relatively minor demands on attention during a psychedelic experience prove to be significant enough distractions from subjective immersion in the experience that they compromise not only the acute phenomenological effects but also the long-term therapeutic benefits of the experience. (Interestingly, 2 days later by publication dates, this finding was independently replicated — here in terms of compromised acute brain effects rather than subjective effects — by Siegel et al., Psilocybin desynchronizes the human brain.)” – CJ Healy
“This quality improvement analysis by Roseman and colleagues explores the concept of “experience efficacy” in psychedelic interventions by investigating whether cognitive interruptions can modulate the subjective experience of N,N-dimethyltryptamine (DMT) and also effects of the intervention on depression scores. Using a secondary analysis of a previous study, the authors examined how asking participants to rate their subjective experiences during DMT altered the intensity and therapeutic impact of the experience. They found that these cognitive interruptions significantly diminished key aspects of the psychedelic state, including feelings of unity, insightfulness, and spiritual experience; factors previously associated with positive mental health outcomes. Participants who were not interrupted exhibited greater reductions in depressive symptoms two weeks later. While the study is limited by a small sample size (N=20) and the relatively mild nature of the interruption, it suggests that contextual manipulation can be a useful tool for studying therapeutic mechanisms of psychedelics and more specifically the relevance of the subjective experience. The authors propose that future research should explore more demanding cognitive interruptions to further elucidate the role of experience in psychedelic-assisted therapy.
In my view, this study is particularly noteworthy as it reinforces the long-standing understanding that contextual factors significantly shape psychedelic experiences and extends this by highlighting the relevance of the experience itself in determining therapeutic outcomes – a topic currently under active discussion in the field (e.g., Olson, 2021; Yaden & Griffiths, 2021). Importantly, the findings also imply that results from prior studies involving acute assessments or experimental tasks during the psychedelic state may have been influenced by those very interventions. This underscores the need for caution when comparing drug effects across studies: Not only should differences in substances and dosages be considered, but also the design of the study protocol including the presence, timing, and modality of any in-session assessments or tasks (e.g., computer-based, verbal, written).
The study affirms that there is no singular or fixed “drug effect,” but rather a highly dynamic and context-sensitive state shaped by both pharmacological and extrapharmacological variables. As previously proposed (e.g., Langlitz, 2024; Roseman et al., 2022), future research should more systematically examine how variations in setting affect the acute subjective experience and downstream clinical outcomes.” – Helena Aicher
Sajid, S., Galfalvy, H. C., Keilp, J. G., Burke, A. K., Mann, J. J., & Grunebaum, M. F. (2024). Acute Dissociation and Ketamine’s Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial. International Journal of Neuropsychopharmacology, 27(4), pyae017. https://doi.org/10.1093/ijnp/pyae017
“Sajid et al. contribute an insightful exploratory analysis addressing conflicting results from previous clinical trials: Is dissociation during ketamine administration an active mechanism responsible for the antidepressant effects or is it a (possibly undesirable) side effect? Using a post-hoc design in participants with depression and suicidal ideation, they found no correlation between dissociation and clinical improvements, suggesting that dissociation is not an active mechanism of ketamine’s therapeutic effects. The study also explores the potential role of ketamine metabolites in producing dissociation, shedding light on how ketamine’s pharmacokinetics may influence its side effects and therapeutic potential.” – Bente Vissel
Siegel, J. S., Subramanian, S., Perry, D., Kay, B. P., Gordon, E. M., Laumann, T. O., Reneau, T. R., Metcalf, N. V., Chacko, R. V., Gratton, C., Horan, C., Krimmel, S. R., Shimony, J. S., Schweiger, J. A., Wong, D. F., Bender, D. A., Scheidter, K. M., Whiting, F. I., Padawer-Curry, J. A., … Dosenbach, N. U. F. (2024). Psilocybin desynchronizes the human brain. Nature, 632(8023), 131–138. https://doi.org/10.1038/s41586-024-07624-5
“High powered precision functional mapping meets psychedelic science. Six healthy adults were scanned multiple times (roughly 18 fMRI visits per subject with rest and task scans at each visit) before, during and for three weeks after high-dose psilocybin and methylphenidate (ritalin). The combination of multiple repeated scanning visits during each period and the use of a stimulant control allowed the authors to study both psilocybin’s acute effects with respect to a heightened arousal state, and psilocybin’s enduring post-acute effects with respect to normal sampling variability. Persistent effects of psilocybin were isolated to an uncoupling of anterior-hippocampal-cortical functional connectivity in the three weeks post-psilocybin that returned to baseline by 6-12 month follow-up visits. Super cool and robust study, plus a Huxley-inspired mage on the cover of Nature magazine.” – S. Parker Singleton
Sloshower, J., Zeifman, R. J., Guss, J., Krause, R., Safi-Aghdam, H., Pathania, S., Pittman, B., & D’Souza, D. C. (2024). Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: Results from an exploratory placebo-controlled trial. Scientific Reports, 14(1), 8833. https://doi.org/10.1038/s41598-024-58318-x
“How do we build a rigorous psychotherapy framework for psychedelic-assisted therapy? Jordan Sloshower and colleagues have been leaders in this space with their long standing focus on Acceptance and Commitment Therapy (ACT) as a well-suited pairing for psychedelics. Their report lends further empirical support for ACT as an evidence-based therapy that can engage psychological flexibility and facilitate drug-specific mechanisms of action for psilocybin.” – David Mathai
Straumann, I., Avedisian, I., Klaiber, A., Varghese, N., Eckert, A., Rudin, D., Luethi, D., & Liechti, M. E. (2024). Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants. Neuropsychopharmacology, 50(2), 362–371. https://doi.org/10.1038/s41386-024-01972-6
“MDMA is a racemic substance that contains equal amounts of the enantiomers S- and R- MDMA. The effects of these enantiomers in humans were qualitatively studied by Dave Nichols, Sasha Shulgin, and their colleagues in the late 1970s after Nichols developed a method of synthesizing the pure enantiomers. These researchers were generally unimpressed by up to 200 mg of the clearly less potent R-enantiomer of MDMA. When methods advanced enough to profile R-MDMA’s effects at monoamine transporters, it appeared to have a profile reminiscent of a less potent MDAI, a compound that the US federal government never bothered to schedule. This all made it somewhat surprising when R- but not S- MDMA was reported to facilitate in mice the extinction of conditioned fear behavior, an animal model with good face validity for studying exposure therapy and recovery from trauma. Interestingly, while R-MDMA improved extinction testing the next day, it did not acutely reduce fear behavior (freezing) during the fear extinction training session. S-MDMA was the opposite: acutely reducing conditioned fear behavior during extinction training, but not helping the next day. Setting aside the fact that mice are an outlier species with respect to MDMA effects, this seemed to set up the possibility that both enantiomers might play distinct and complementary roles in the therapeutic effects of MDMA. And given the known greater chronic monoamine lowering effects of the S-enantiomer, this also seemed to justify exploration of R-heavy mixtures or even pure R-MDMA as a therapeutic adjunct. (Weighing somewhat against this approach is an early finding that R- was equipotent to S- MDMA in acutely lowering tryptophan hydroxylase, a putative marker of oxidative stress. Because R has the lower potency and thus requires higher doses, this raises questions how much higher oxidative stress might be with effective doses of R.)
Against this background, the current MDMA-administration study from Staumann et al. is a much needed investigation of the acute pharmacology of MDMA’s enantiomers in 24 healthy participants. The five dosing conditions – placebo, 125 mg of racemic MDMA, 125 mg of S-MDMA, 125 and 250 mg of R-MDMA – were selected to facilitate comparisons between the enantiomers. However, 125 mg S-MDMA appeared distinctly more active than the 250 mg dose of R, suggesting the selected doses were not quite comparable. (It’s not obvious how to best select doses of different drugs for the purposes of comparing them, especially without any pharmacokinetics, but it would seem reasonable to ask that psychoactive drugs be comparable on self-reported ‘any drug effect’ or similar.) Disappointingly, the enantiomers did not have dramatically different qualitative pharmacological profiles, at least not given the current study’s measures. Proponents of the potential value of the R-enantiomer might point out that there were no measures that would be analogous to the improved fear extinction seen in mice. Thus, it remains to be seen if R-MDMA might have clearer value when, for example, paired with some type of exposure therapy. Still, even if the study proved disappointing for those of us hoping to improve on racemic MDMA, the study nonetheless provides a wealth of careful pharmacokinetics and dynamics information. Having a clean measure of the elimination half-lives of the enantiomers, independent from their competition when given together, is valuable. The shortened half-life of S-MDMA given alone compared to when given as part of racemic MDMA suggests that part of the appeal of racemic MDMA might be that the presence of the R-MDMA is extending exposure to the more active S-MDMA. It is additionally intriguing that the S-enantiomer was the only treatment to significantly lower mood ratings in the days after administration, providing hints to the potential mechanism of this elusive phenomenon.” – Matthew Baggott
Szigeti, B., Weiss, B., Rosas, F. E., Erritzoe, D., Nutt, D., & Carhart-Harris, R. (2024). Assessing expectancy and suggestibility in a trial of escitalopram v. Psilocybin for depression. Psychological Medicine, 54(8), 1717–1724. https://doi.org/10.1017/S0033291723003653
“Compelling evidence against the notion that the therapeutic benefits of psychedelics are largely or entirely driven by placebo effects.” – CJ Healy
The above publications received comments from the researchers we surveyed. Here are further 2024 publications that Michael included in his list.
***
Ables, J. L., Israel, L., Wood, O., Govindarajulu, U., Fremont, R. T., Banerjee, R., Liu, H., Cohen, J., Wang, P., Kumar, K., Lu, G., DeVita, R. J., Garcia-Ocaña, A., Murrough, J. W., & Stewart, A. F. (2024). A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers. Journal of Psychopharmacology, 38(10), 911–923. https://doi.org/10.1177/02698811241273772
Aicher, H. D., Mueller, M. J., Dornbierer, D. A., Suay, D., Elsner, C., Wicki, I., Meling, D., Caflisch, L., Hempe, A., Steinhart, C., Mueller, J., Von Rotz, R., Kleim, B., & Scheidegger, M. (2024). Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: A controlled trial in healthy subjects. Frontiers in Psychiatry, 14, 1302559. https://doi.org/10.3389/fpsyt.2023.1302559
Armand, S., Larsen, K., Madsen, M. K., Ozenne, B., Preller, K. H., Knudsen, G. M., Stenbæk, D. S., & Fisher, P. M. (2024). Amygdala response to emotional faces following acute administration of psilocybin in healthy individuals. Neuroscience Applied, 3, 103934. https://doi.org/10.1016/j.nsa.2023.103934
Avram, M., Fortea, L., Wollner, L., Coenen, R., Korda, A., Rogg, H., Holze, F., Vizeli, P., Ley, L., Radua, J., Müller, F., Liechti, M. E., & Borgwardt, S. (2024). Large-scale brain connectivity changes following the administration of lysergic acid diethylamide, d-amphetamine, and 3,4-methylenedioxyamphetamine. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02734-y
Beaglehole, B., Glue, P., Neehoff, S., Shadli, S., McNaughton, N., Kimber, B., Muirhead, C., Bie, A. D., Day-Brown, R., & Hughes-Medlicott, N. J. (2024). Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study. Journal of Psychopharmacology, 39(1), 23–28. https://doi.org/10.1177/02698811241301215
Bershad, A. K., Hsu, D. T., & De Wit, H. (2024). MDMA enhances positive affective responses to social feedback. Journal of Psychopharmacology, 38(3), 297–304. https://doi.org/10.1177/02698811231224153
Bonnelle, V., Feilding, A., Rosas, F. E., Nutt, D. J., Carhart-Harris, R. L., & Timmermann, C. (2024). Autonomic nervous system activity correlates with peak experiences induced by DMT and predicts increases in well-being. Journal of Psychopharmacology.
Casanova, A. F., Ort, A., Smallridge, J. W., Preller, K. H., Seifritz, E., & Vollenweider, F. X. (2024). The influence of psilocybin on subconscious and conscious emotional learning. iScience, 27(6), 110034. https://doi.org/10.1016/j.isci.2024.110034
DiRenzo, D., Barrett, F. S., Perin, J., Darrah, E., Christopher-Stine, L., & Griffiths, R. R. (2024). Impact of Psilocybin on Peripheral Cytokine Production. Psychedelic Medicine, 2(2), 109–115. https://doi.org/10.1089/psymed.2023.0039
Doss, M. K., Mallaroni, P., Mason, N. L., & Ramaekers, J. G. (2024). Psilocybin and 2C-B at Encoding Distort Episodic Familiarity. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 9(10), 1048–1057. https://doi.org/10.1016/j.bpsc.2024.06.008
Ellis, S., Bostian, C., Feng, W., Fischer, E., Schwartz, G., Eisen, K., Lean, M., Conlan, E., Ostacher, M., Aaronson, S., & Suppes, T. (2024). Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression – A first-in-kind open-label pilot study. Journal of Affective Disorders, 369, 381–389. https://doi.org/10.1016/j.jad.2024.09.133
Enriquez-Geppert, S., Krc, J., O’Higgins, F. J., & Lietz, M. (2024). Psilocybin-assisted neurofeedback for the improvement of executive functions: A randomized semi-naturalistic-lab feasibility study. Philosophical Transactions of the Royal Society B: Biological Sciences, 379(1915), 20230095. https://doi.org/10.1098/rstb.2023.0095
Erne, L., Vogt, S. B., Müller, L., Nuraj, A., Becker, A., Klaiber, A., Zuparic, M., Varghese, N., Eckert, A., Rudin, D., Luethi, D., & Liechti, M. E. (2024). Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacology. https://doi.org/10.1038/s41386-024-02041-8
Erritzoe, D., Barba, T., Greenway, K. T., Murphy, R., Martell, J., Giribaldi, B., Timmermann, C., Murphy-Beiner, A., Jones, M. B., Nutt, D., Weiss, B., & Carhart-Harris, R. (2024). Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: Observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. eClinicalMedicine, 76, 102799. https://doi.org/10.1016/j.eclinm.2024.102799
Erritzoe, D., Barba, T., Spriggs, M. J., Rosas, F. E., Nutt, D. J., & Carhart-Harris, R. (2024). Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression. Journal of Psychopharmacology, 38(5), 458–470. https://doi.org/10.1177/02698811241237870
Falchi-Carvalho, M., Barros, H., Bolcont, R., Laborde, S., Wießner, I., Ruschi B. Silva, S., Montanini, D., Barbosa, D. C., Teixeira, E., Florence-Vilela, R., Almeida, R., De Macedo, R. K. A., Arichelle, F., Pantrigo, É. J., Costa-Macedo, J. V., Arcoverde, E., Galvão-Coelho, N., Araujo, D. B., & Palhano-Fontes, F. (2024). The Antidepressant Effects of Vaporized N , N -Dimethyltryptamine: An Open-Label Pilot Trial in Treatment-Resistant Depression. Psychedelic Medicine, psymed.2024.0002. https://doi.org/10.1089/psymed.2024.0002
Falchi-Carvalho, M., Wießner, I., Silva, S. R. B., O Maia, L., Barros, H., Laborde, S., Arichelle, F., Tullman, S., Silva-Costa, N., Assunção, A., Almeida, R., Pantrigo, É. J., Bolcont, R., Costa-Macedo, J. V., Arcoverde, E., Galvão-Coelho, N., Araujo, D. B., & Palhano-Fontes, F. (2024). Safety and tolerability of inhaled N,N-Dimethyltryptamine (BMND01 candidate): A phase I clinical trial. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 80, 27–35. https://doi.org/10.1016/j.euroneuro.2023.12.006
Gent, E. M., Bryan, J. W., Cleary, M. A., Clarke, T. I., Holmwood, H. D., Nassereddine, R. O., Salway, C., Depla, S., Statton, S., Krecké, J., & Morgan, C. J. (2024). Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems. Journal of Psychopharmacology, 38(6), 541–550. https://doi.org/10.1177/02698811241254834
Glue, P., Neehoff, S., Beaglehole, B., Shadli, S., McNaughton, N., & Hughes-Medlicott, N. J. (2024). Ketamine for treatment-resistant major depressive disorder: Double-blind active-controlled crossover study. Journal of Psychopharmacology, 38(2), 162–167. https://doi.org/10.1177/02698811241227026
Godfrey, K., Weiss, B., Zhang, X., Spriggs, M., Peill, J., Lyons, T., Carhart-Harris, R., & Erritzoe, D. (2024). An investigation of acute physiological and psychological moderators of psychedelic-induced personality change among healthy volunteers. Neuroscience Applied, 4, 104092. https://doi.org/10.1016/j.nsa.2024.104092
Goodwin, G. M., Aaronson, S. T., Alvarez, O., Carhart-Harris, R., Chai-Rees, J., Croal, M., DeBattista, C., Dunlop, B. W., Feifel, D., Hellerstein, D. J., Husain, M. I., Kelly, J. R., Kirlic, N., Licht, R. W., Marwood, L., Meyer, T. D., Mistry, S., Nowakowska, A., Páleníček, T., … Malievskaia, E. (2024). The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression. Journal of Affective Disorders, 372, 523–532. https://doi.org/10.1016/j.jad.2024.12.061
Haggarty, C. J., Bershad, A. K., Kumar, M. K., Lee, R., & De Wit, H. (2024). The 3,4‐methylenedioxymethamphetamine enhances early visual processing for salient socio‐emotional stimuli. European Journal of Neuroscience, 59(12), 3224–3235. https://doi.org/10.1111/ejn.16346
Hess, E. M., Greenstein, D. K., Hutchinson, O. L., Zarate, C. A., & Gould, T. D. (2024). Entactogen Effects of Ketamine: A Reverse-Translational Study. American Journal of Psychiatry, 181(9), 815–823. https://doi.org/10.1176/appi.ajp.20230980
Holze, F., Gasser, P., Müller, F., Strebel, M., & Liechti, M. E. (2024). LSD-assisted therapy in patients with anxiety: Open-label prospective 12-month follow-up. The British Journal of Psychiatry, 225(3), 362–370. https://doi.org/10.1192/bjp.2024.99
Holze, F., Madsen, M. K., Svarer, C., Gillings, N., Stenbaek, D. S., Rudin, D., Duthaler, U., Liechti, M. E., Fisher, P. M., & Knudsen, G. M. (2024). Ketanserin exhibits dose- and concentration-proportional serotonin 2A receptor occupancy in healthy individuals: Relevance for psychedelic research. European Neuropsychopharmacology, 88, 43–48. https://doi.org/10.1016/j.euroneuro.2024.07.003
Hutten, N. R. P. W., Quaedflieg, C. W. E. M., Mason, N. L., Theunissen, E. L., Liechti, M. E., Duthaler, U., Kuypers, K. P. C., Bonnelle, V., Feilding, A., & Ramaekers, J. G. (2024). Inter-individual variability in neural response to low doses of LSD. Translational Psychiatry, 14(1), 288. https://doi.org/10.1038/s41398-024-03013-8
James, E., Erritzoe, D., Benway, T., Joel, Z., Timmermann, C., Good, M., Agnorelli, C., Weiss, B. M., Barba, T., Campbell, G., Baker Jones, M., Hughes, C., Topping, H., Boyce, M., & Routledge, C. (2024). Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: A randomized, placebo-controlled phase 1 trial. Frontiers in Psychiatry, 14, 1305796. https://doi.org/10.3389/fpsyt.2023.1305796
Jha, M. K., Wilkinson, S. T., Krishnan, K., Collins, K. A., Sanacora, G., Murrough, J., Goes, F., Altinay, M., Aloysi, A., Asghar-Ali, A., Barnett, B., Chang, L., Costi, S., Malone, D., Nikayin, S., Nissen, S. E., Ostroff, R., Reti, I., Wolski, K., … Anand, A. (2024). Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial. JAMA Network Open, 7(6), e2417786. https://doi.org/10.1001/jamanetworkopen.2024.17786
Klaiber, A., Humbert‐Droz, M., Ley, L., Schmid, Y., & Liechti, M. E. (2024). Safety pharmacology of acute mescaline administration in healthy participants. British Journal of Clinical Pharmacology, bcp.16349. https://doi.org/10.1111/bcp.16349
Klaiber, A., Schmid, Y., Becker, A. M., Straumann, I., Erne, L., Jelusic, A., Thomann, J., Luethi, D., & Liechti, M. E. (2024). Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects. Translational Psychiatry, 14(1), 395. https://doi.org/10.1038/s41398-024-03116-2
Knuijver, T., Ter Heine, R., Schellekens, A. F. A., Heydari, P., Lucas, L., Westra, S., Belgers, M., Van Oosteren, T., Verkes, R. J., & Kramers, C. (2024). The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients. Journal of Psychopharmacology, 38(5), 481–488. https://doi.org/10.1177/02698811241237873
Lewis-Healey, E., Tagliazucchi, E., Canales-Johnson, A., & Bekinschtein, T. A. (2024). Breathwork-induced psychedelic experiences modulate neural dynamics. Cerebral cortex (New York, N.Y. : 1991), 34(8), bhae347. https://doi.org/10.1093/cercor/bhae347
Madsen, M. K., Petersen, A. S., Stenbæk, D. S., Sørensen, I. M., Schiønning, H., Fjeld, T., Nykjær, C. H., Larsen, S. M. U., Grzywacz, M., Mathiesen, T., Klausen, I. L., Overgaard‐Hansen, O., Brendstrup‐Brix, K., Linnet, K., Johansen, S. S., Fisher, P. M., Jensen, R. H., & Knudsen, G. M. (2024). CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity. Headache: The Journal of Head and Face Pain, 64(1), 55–67. https://doi.org/10.1111/head.14656
Marwood, L., Croal, M., Mistry, S., Simmons, H., Tsai, J., Young, M. B., & Goodwin, G. M. (2024). The impact of antidepressant discontinuation prior to treatment with psilocybin for treatment-resistant depression. Journal of Psychiatric Research, 180, 198–203. https://doi.org/10.1016/j.jpsychires.2024.10.009
Mediano, P. A. M., Rosas, F. E., Timmermann, C., Roseman, L., Nutt, D. J., Feilding, A., Kaelen, M., Kringelbach, M. L., Barrett, A. B., Seth, A. K., Muthukumaraswamy, S., Bor, D., & Carhart-Harris, R. L. (2024). Effects of External Stimulation on Psychedelic State Neurodynamics. ACS Chemical Neuroscience, 15(3), 462–471. https://doi.org/10.1021/acschemneuro.3c00289
Meling, D., Egger, K., Aicher, H. D., Jareño Redondo, J., Mueller, J., Dornbierer, J., Temperli, E., Vasella, E. A., Caflisch, L., Pfeiffer, D. J., Schlomberg, J. T., Smallridge, J. W., Dornbierer, D. A., & Scheidegger, M. (2024). Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat. Journal of Psychopharmacology, 38(10), 897–910. https://doi.org/10.1177/02698811241282637
Meshkat, S., Kaczmarek, E., Doyle, Z., Brudner, R. M., Gomes, F. A., Blainey, M. G., Weiglein, G., McIntyre, R. S., Mansur, R. B., & Rosenblat, J. D. (2024). Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder. Psychedelic Medicine, psymed.2024.0032. https://doi.org/10.1089/psymed.2024.0032
Molla, H., Novembre, G., Bershad, A., Handlin, L., Perini, I., De Wit, H., & Morrison, I. (2024). MDMA modulates human sensorimotor cortical pathways during gentle touch. Imaging Neuroscience, 2, 1–15. https://doi.org/10.1162/imag_a_00316
Moujaes, F., Ji, J. L., Rahmati, M., Burt, J. B., Schleifer, C., Adkinson, B. D., Savic, A., Santamauro, N., Tamayo, Z., Diehl, C., Kolobaric, A., Flynn, M., Rieser, N., Fonteneau, C., Camarro, T., Xu, J., Cho, Y., Repovs, G., Fineberg, S. K., … Anticevic, A. (2024). Ketamine induces multiple individually distinct whole-brain functional connectivity signatures. eLife, 13, e84173. https://doi.org/10.7554/eLife.84173
Murray, C. H., Frohlich, J., Haggarty, C. J., Tare, I., Lee, R., & De Wit, H. (2024). Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine. Neuropsychopharmacology, 49(7), 1120–1128. https://doi.org/10.1038/s41386-024-01809-2
Pagni, B. A., Petridis, P. D., Podrebarac, S. K., Grinband, J., Claus, E. D., & Bogenschutz, M. P. (2024). Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: An fMRI pilot study. Scientific Reports, 14(1), 3159. https://doi.org/10.1038/s41598-024-52967-8
Pagni, B. A., Zeifman, R. J., Mennenga, S. E., Carrithers, B. M., Goldway, N., Bhatt, S., O’Donnell, K. C., Ross, S., & Bogenschutz, M. P. (2024). Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial. American Journal of Psychiatry, 182(1), 114–125. https://doi.org/10.1176/appi.ajp.20230887
Pais, M. L., Teixeira, M., Soares, C., Lima, G., Rijo, P., Cabral, C., & Castelo-Branco, M. (2024). Rapid effects of tryptamine psychedelics on perceptual distortions and early visual cortical population receptive fields. NeuroImage, 297, 120718. https://doi.org/10.1016/j.neuroimage.2024.120718
Palhano-Fontes, F., Cavalcanti-Ribeiro, P., Da Costa Gonçalves, K. T., De Almeida, V. R. N., Barbosa, D. C., De Araújo Ferreira, M. A., Bolcont, R., De Souza, L. C. A. M., Santos, N. C., Lopes, E. I. T. C., De Medeiros Lima, N. B., De Brito, A. J. C., Falchi-Carvalho, M., Arcoverde, E., Araujo, D., & Galvão-Coelho, N. L. (2024). Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study. Journal of Affective Disorders, 369, 155–163. https://doi.org/10.1016/j.jad.2024.09.141
Parikh, S. V., Vande Voort, J. L., Yocum, A. K., Achtyes, E., Goes, F. S., Nykamp, L., Singh, B., Lopez-Vives, D., Sera, C. E., Maixner, D., Tarnal, V., Severe, J., Bartek, S., Tye, S. J., Rico, J., Stoppel, C. J., Becerra, A., Smart, L., Miller, C. R., … Bobo, W. V. (2024). Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression. Journal of Affective Disorders, 348, 143–151. https://doi.org/10.1016/j.jad.2023.12.033
Peill, J., Marguilho, M., Erritzoe, D., Barba, T., Greenway, K. T., Rosas, F., Timmermann, C., & Carhart-Harris, R. (2024). Psychedelics and the ‘inner healer’: Myth or mechanism? Journal of Psychopharmacology, 38(5), 417–424. https://doi.org/10.1177/02698811241239206
Petridis, P. D., Grinband, J., Agin-Liebes, G., Kinslow, C. J., Zeifman, R. J., Bogenschutz, M. P., Griffiths, R. R., & Ross, S. (2024). Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer. Nature Mental Health, 2(11), 1408–1414. https://doi.org/10.1038/s44220-024-00331-0
Ramaekers, J. G., Reckweg, J. T., Mason, N. L., Kuypers, K. P. C., Toennes, S. W., & Theunissen, E. L. (2024). Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): A first in human, designer drug study. Neuropsychopharmacology. https://doi.org/10.1038/s41386-024-02042-7
Rodrigues, L. S., Reis, J. A. S., Rossi, G. N., Guerra, L. T. L., Maekawa, R. M., De Lima Osório, F., Bouso, J. C., Santos, F. P., Paranhos, B. A. P. B., Yonamine, M., Hallak, J. E. C., & Dos Santos, R. G. (2024). Effects of a Single Dose of Ayahuasca in College Students With Harmful Alcohol Use: A Single-blind, Feasibility, Proof-of-Concept Trial. Journal of Clinical Psychopharmacology. https://doi.org/10.1097/JCP.0000000000001872
Rosenblat, J. D., Meshkat, S., Doyle, Z., Kaczmarek, E., Brudner, R. M., Kratiuk, K., Mansur, R. B., Schulz-Quach, C., Sethi, R., Abate, A., Ali, S., Bawks, J., Blainey, M. G., Brietzke, E., Cronin, V., Danilewitz, J., Dhawan, S., Di Fonzo, A., Di Fonzo, M., … McIntyre, R. S. (2024). Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin. Med, 5(3), 190-200.e5. https://doi.org/10.1016/j.medj.2024.01.005
Rucker, J., Butler, M., Hambleton, S., Bird, C., Seynaeve, M., Cheema, S., Campbell‐Coker, K., Maggio, C., Dunbar, F., Lambru, G., & Matharu, M. (2024). Low‐dose psilocybin in short‐lasting unilateral neuralgiform headache attacks: Results from an open‐label phase Ib ascending dose study. Headache: The Journal of Head and Face Pain, 64(10), 1309–1317. https://doi.org/10.1111/head.14837
Rucker, J. J., Roberts, C., Seynaeve, M., Young, A. H., Suttle, B., Yamamoto, T., Ermakova, A. O., Dunbar, F., & Wiegand, F. (2024). Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy- N,N -dimethyltryptamine benzoate) in healthy participants. Journal of Psychopharmacology, 38(8), 712–723. https://doi.org/10.1177/02698811241246857
Schindler, E. A. D., Sewell, R. A., Gottschalk, C. H., Flynn, L. T., Zhu, Y., Pittman, B. P., Cozzi, N. V., & D’Souza, D. C. (2024). Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial. Journal of the Neurological Sciences, 460, 122993. https://doi.org/10.1016/j.jns.2024.122993
Searchfield, G. D., Poppe, T. N. E. R., Durai, M., Jensen, M., Kennedy, M. A., Maggo, S., Miller, A. L., Park, J., Russell, B. R., Shekhawat, G. S., Spiegel, D., Sundram, F., & Wise, K. (2020). A proof-of-principle study of the short-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus and neural connectivity. International Journal of Neuroscience, 130(7), 671–682. https://doi.org/10.1080/00207454.2019.1702544
Smith-Apeldoorn, S. Y., Veraart, J. K. E., Kamphuis, J., Spijker, J., Van Der Meij, A., Van Asselt, A. D. I., Aan Het Rot, M., & Schoevers, R. A. (2024). Oral esketamine in patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial with open-label extension. Molecular Psychiatry, 29(9), 2657–2665. https://doi.org/10.1038/s41380-024-02478-9
Stoliker, D., Novelli, L., Vollenweider, F. X., Egan, G. F., Preller, K. H., & Razi, A. (2024). Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin. Biological Psychiatry, 96(1), 57–66. https://doi.org/10.1016/j.biopsych.2024.01.002
Stoliker, D., Preller, K. H., Novelli, L., Anticevic, A., Egan, G. F., Vollenweider, F. X., & Razi, A. (2024). Neural mechanisms of psychedelic visual imagery. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02632-3
Straumann, I., Holze, F., Becker, A. M., Ley, L., Halter, N., & Liechti, M. E. (2024). Safety pharmacology of acute psilocybin administration in healthy participants. Neuroscience Applied, 3, 104060. https://doi.org/10.1016/j.nsa.2024.104060
Sumner, R. L., McMillan, R. L., Forsyth, A., Muthukumaraswamy, S. D., & Shaw, A. D. (2024). Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine. Translational Psychiatry, 14(1), 116. https://doi.org/10.1038/s41398-024-02738-w
Swanson, L. R., Jungers, S., Varghese, R., Cullen, K. R., Evans, M. D., Nielson, J. L., & Schallmo, M.-P. (2024). Enhanced visual contrast suppression during peak psilocybin effects: Psychophysical results from a pilot randomized controlled trial. Journal of Vision, 24(12), 5. https://doi.org/10.1167/jov.24.12.5
Timmermann, C., Zeifman, R. J., Erritzoe, D., Nutt, D. J., & Carhart-Harris, R. L. (2024). Effects of DMT on mental health outcomes in healthy volunteers. Scientific Reports, 14(1), 3097. https://doi.org/10.1038/s41598-024-53363-y
Vizeli, P., Studerus, E., Holze, F., Schmid, Y., Dolder, P. C., Ley, L., Straumann, I., Becker, A. M., Müller, F., Arikci, D., & Liechti, M. E. (2024). Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants. Translational Psychiatry, 14(1), 357. https://doi.org/10.1038/s41398-024-03074-9
Woody, M. L., Rohac, R., Cooper, I., Griffo, A., McDonald, N., Spotts, C., Fournier, J., Jones, N., Peciña, M., Young, K., Shivanekar, S., Rengasamy, M., Grafton, B., & Price, R. B. (2024). The Impact of Intravenous Ketamine on Attentional Bias: Probing Mechanisms of Rapid-Acting Antidepressant Effects Across Two Clinical Studies. Biological Psychiatry, S000632232401758X. https://doi.org/10.1016/j.biopsych.2024.10.024
Zeifman, R. J., Kettner, H., Ross, S., Weiss, B., Mithoefer, M. C., Mithoefer, A. T., & Wagner, A. C. (2024). Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder. European Journal of Psychotraumatology, 15(1), 2297536. https://doi.org/10.1080/20008066.2023.2297536
Zhu, X., Zhang, C., Hellerstein, D., Feusner, J. D., Wheaton, M. G., Gomez, G. J., & Schneier, F. (2024). Single-dose psilocybin alters resting state functional networks in patients with body dysmorphic disorder. Psychedelics, 1–7. https://doi.org/10.61373/pp024r.0028
Discovery & Preclinical
Alberto‐Silva, A. S., Hemmer, S., Bock, H. A., Da Silva, L. A., Scott, K. R., Kastner, N., Bhatt, M., Niello, M., Jäntsch, K., Kudlacek, O., Bossi, E., Stockner, T., Meyer, M. R., McCorvy, J. D., Brandt, S. D., Kavanagh, P., & Sitte, H. H. (2024). Bioisosteric analogs of MDMA: Improving the pharmacological profile? Journal of Neurochemistry, 168(9), 2022–2042. https://doi.org/10.1111/jnc.16149
“MDMA’s oxygen-containing side ring is readily metabolized in the body into two hydroxyl groups, creating a reactive metabolite that resembles dopamine. A large and somewhat contradictory literature has investigated whether this and downstream metabolites might contribute to the toxicity of MDMA. If these metabolites really are toxicologically important, there could be great value in finding new chemical structures that resist metabolism but are otherwise pharmacologically similar to MDMA. The current paper describes three novel replacements for MDMA’s side ring and shows they successfully resist metabolism while still causing the monoamine release that is predictive of acute MDMA-like emotional effects. However, without animal assays, we cannot yet tell whether these promising analogues are truly entactogens. The authors also report reduced activity at 5-HT2A/2B/2C receptors, although MDMA’s effects at these receptors are weak enough that it remains unclear how much direct agonist effects at 5-HT2Rs contribute to its pharmacology at therapeutic exposures. There is certainly evidence that valvular heart disease can occur with extensive MDMA use, but this may be caused indirectly, by released 5-HT stimulating 5-HT2BRs. An interesting question would be whether the corresponding MDA analogues of this paper’s compounds, which would be expected to be better 5-HT2R agonists, also show reduced 5-HT2R activity.” – Matthew Baggott
Alitalo, O., Kohtala, S., Rosenholm, M., Saarreharju, R., González-Hernández, G., Sarparanta, M., Rozov, S., & Rantamäki, T. (2024). Nitrous oxide induces hypothermia and TrkB activation: Maintenance of body temperature abolishes antidepressant-like effects in mice. Neuropharmacology, 261, 110172. https://doi.org/10.1016/j.neuropharm.2024.110172
“The paper by Alitalo et al. extends their previous findings linking body temperature and TrkB signalling, this time also adding some antidepressant–relevant behavioural outcomes. Their finding where the modification of body temperature of an animal changes both the neurotrophic signalling and behavioural effects of a drug is highly intriguing. Even though their drug of choice, nitrous oxide, is often not considered a psychedelic, the relevance to classical serotonergic psychedelics and ketamine is obvious, as TrkB signalling pathway has been implicated in their actions in many ways, directly and indirectly. As with any neurotrophin– and plasticity–related findings, the translation to humans and clinical relevance remain to be demonstrated, but I am interested and happy in seeing this kind of physiology-as-a-whole approach in psychopharmacology.” – Lauri Elsilä
Anderson, T. L., Keady, J. V., Songrady, J., Tavakoli, N. S., Asadipooya, A., Neeley, R. E., Turner, J. R., & Ortinski, P. I. (2024). Distinct 5-HT receptor subtypes regulate claustrum excitability by serotonin and the psychedelic, DOI. Progress in Neurobiology, 240, 102660. https://doi.org/10.1016/j.pneurobio.2024.102660
“I had to give this paper a shout out because it had been a long time coming. I remember seeing a presentation at Society for Neuroscience on some of this work in 2023 and then was so excited to see the complete work published this past year. My favorite thing about this study is that it looks at projections from the claustrum to the cortex instead of projections from the cortex to other brain regions, which is what we typically see in preclinical circuitry studies. They find that the claustrum is enriched primarily with serotonin 2C receptors on excitatory neurons and that there are differential effects of serotonin and DOI on the signaling in this region. These findings break the mold of the canonical serotonin 2A receptor pathway as a mechanism of action for psychedelics and open the door to an entirely new line of research in the field.” – Alaina Jaster
Braun, D., Rosenberg, A. M., Rabaniam, E., Haruvi, R., Malamud, D., Barbara, R., Aiznkot, T., Levavi-Sivan, B., & Kawashima, T. (2024). High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin. Molecular Psychiatry, 29(4), 1046–1062. https://doi.org/10.1038/s41380-023-02391-7
“I find myself thinking more about how to make our research useful for drug discovery. Cell lines are sometimes too simplistic, but mouse experiments take a long time. Here, this study shows that zebrafish behavioral assay may be a promising approach for high throughput screens with live animals. The authors did a very thorough job in quantifying how psilocybin affects the fishes’ movements, which was distinct from those changes elicited by ketamine and fluoxetine.” – Alex Kwan
Hinchcliffe, J. K., Stuart, S. A., Wood, C. M., Bartlett, J., Kamenish, K., Arban, R., Thomas, C. W., Selimbeyoglu, A., Hurley, S., Hengerer, B., Gilmour, G., & Robinson, E. S. J. (2024). Rapid-acting antidepressant drugs modulate affective bias in rats. Science Translational Medicine, 16(729), eadi2403. https://doi.org/10.1126/scitranslmed.adi2403
“The paper led by Justyna Hinchcliffe and Emma Robinson is one of my favourites from the previous year. The findings themselves are interesting, but I greatly appreciate their efforts in developing rodent models that have better translational validity: as far as I know, the effects of psychedelics and ketamine are and have already been studied in a human version of affective bias test with similar results. (I personally also love to see a paper with only behavioural results published in such a high impact journal, it gives me hope).” – Lauri Elsilä
Jeanblanc, J., Bordy, R., Fouquet, G., Jeanblanc, V., & Naassila, M. (2024). Psilocybin reduces alcohol self-administration via selective left nucleus accumbens activation in rats. Brain, 147(11), 3780–3788. https://doi.org/10.1093/brain/awae136
“The findings by Jerome Jeanblanc and others are highly interesting to me as a preclinical addiction researcher: it is an addition to the literature where a single dose of psychedelic reduces alcohol consumption in rodents, this time in rats, but it further emphasises the interesting question – where do the differences in effects and their lengths in the rodent models of alcohol use stem from? Why do some only see acute effects, some prolonged, and some no effects at all? Is it about the drinking levels and styles (operant vs. home cage, binge vs. continuous?) or about the treatment schedule? Their findings also raise interesting questions about the lateralisation of the rat brain and its reward system worth further enquiry.” – Lauri Elsilä
Pohořalá, V., Kuchař, M., Spanagel, R., & Bernardi, R. E. (2024). Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice. Neuroscience, 559, 156–165. https://doi.org/10.1016/j.neuroscience.2024.09.006
“As someone who spent several years researching psychedelics in preclinical models related to addiction, I can appreciate this study. They aimed to understand how psilocybin can alter cocaine-seeking behaviors in models of self-administration. Not only did this study use male and female mice to understand differences across sexes, but they also tested extinction of drug-seeking and cue-induced reinstatement of drug-seeking. While the authors found no effects of psilocybin on cocaine cue reinstatement, this could be due to when the psilocybin was administered. This study provides a great start to understanding the addiction-related processes and how psychedelics can reduce drug-seeking. More studies assessing different time points of administration of psilocybin and the extinction process will be an exciting addition to the field.” – Alaina Jaster
Tiwari, P., Davoudian, P. A., Kapri, D., Vuruputuri, R. M., Karaba, L. A., Sharma, M., Zanni, G., Balakrishnan, A., Chaudhari, P. R., Pradhan, A., Suryavanshi, S., Bath, K. G., Ansorge, M. S., Fernandez-Ruiz, A., Kwan, A. C., & Vaidya, V. A. (2024). Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI. Neuron, 112(22), 3697-3714.e6. https://doi.org/10.1016/j.neuron.2024.08.016
“This was another long-awaited publication in the preclinical sciences. I’m such a sucker for a paper with a circuit component and this paper delivers. The authors were interested in determining how psychedelics produce their anxiolytic effects in rodent models. They combined multiple sophisticated techniques in both rats and mice, to produce a large body of work showing that the acute anxiolytic effects of psychedelic DOI and the cell-types involved are preserved across rodent species. While the work focused primarily on the acute effects of DOI, I would be very interested to see if this anxiolysis is observed post-acutely and whether the same cell types are responsible for those potential post-acute effects.” – Alaina Jaster
Warren, A. L., Lankri, D., Cunningham, M. J., Serrano, I. C., Parise, L. F., Kruegel, A. C., Duggan, P., Zilberg, G., Capper, M. J., Havel, V., Russo, S. J., Sames, D., & Wacker, D. (2024). Structural pharmacology and therapeutic potential of 5-methoxytryptamines. Nature, 630(8015), 237–246. https://doi.org/10.1038/s41586-024-07403-2
“Despite a long history of ritual, traditional, and more-recent clinical therapeutic use, 5-MeO-DMT is an understudied tryptamine – few explorations of the drug’s molecular underpinnings and mechanism of action exist. Warren et al. provide pharmacological profiles of 5-MeO-DMT and associated analogues, structural and morphological profiles of 5-MeO-DMT and highlight the 5-HT1A receptor as a locus of therapeutic activity. This work seems to align with an outstanding question in the field – are hallucinogenic effects necessary for therapeutic benefits? What I am left thinking about is how we continually see derivatives and analogues of naturally-occurring compounds synthesized and monopolized, without considering or appreciating historical and cultural practices and knowledge.” – Juliet Meccia
The above publications received comments from the researchers we surveyed. Here are further 2024 publications that Michael included in his list.
***
Abate, C., Young, R., Dukat, M., & Glennon, R. A. (2024). Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET. Psychopharmacology. https://doi.org/10.1007/s00213-024-06738-y
Abbott, J. A., Wen, H., Liu, B., Gupta, S. S., Iacobucci, G. J., Zheng, W., & Popescu, G. K. (2024). Allosteric inhibition of NMDA receptors by low dose ketamine. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02729-9
Arias, H. R., Rudin, D., Hines, D. J., Contreras, A., Gulsevin, A., Manetti, D., Anouar, Y., De Deurwaerdere, P., Meiler, J., Romanelli, M. N., Liechti, M. E., & Chagraoui, A. (2024). The novel non-hallucinogenic compound DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole) induces sedative- and anxiolytic-like activity in mice by a mechanism involving 5-HT2A receptor activation. European Journal of Pharmacology, 966, 176329. https://doi.org/10.1016/j.ejphar.2024.176329
Arias, H. R., Rudin, D., Luethi, D., Valenta, J., Leśniak, A., Czartoryska, Z., Olejarz-Maciej, A., Doroz-Płonka, A., Manetti, D., De Deurwaerdère, P., Romanelli, M. N., Handzlik, J., Liechti, M. E., & Chagraoui, A. (2024). The psychoplastogens ibogaminalog and ibogainalog induce antidepressant-like activity in naïve and depressed mice by mechanisms involving 5-HT2A receptor activation and serotonergic transmission. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 136, 111217. https://doi.org/10.1016/j.pnpbp.2024.111217
Bagdasarian, F. A., Hansen, H. D., Chen, J., Yoo, C.-H., Placzek, M. S., Hooker, J. M., & Wey, H.-Y. (2024). Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A. ACS Chemical Neuroscience, 15(14), 2654–2661. https://doi.org/10.1021/acschemneuro.4c00245
Baraghithy, S., Gammal, A., Permyakova, A., Hamad, S., Kočvarová, R., Calles, Y., & Tam, J. (2024). 5-Methoxy-2-aminoindane Reverses Diet-Induced Obesity and Improves Metabolic Parameters in Mice: A Potential New Class of Antiobesity Therapeutics. ACS Pharmacology & Translational Science, 7(8), 2527–2543. https://doi.org/10.1021/acsptsci.4c00353
Bassi, M., Bilel, S., Tirri, M., Corli, G., Di Rosa, F., Gregori, A., Alkilany, A. M., Rachid, O., Roda, E., Zauli, G., Locatelli, C. A., & Marti, M. (2024). Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice—From a human poisoning case to the preclinical evidence. Psychopharmacology, 241(3), 489–511. https://doi.org/10.1007/s00213-024-06526-8
Berman, P., De Haro, L. A., Cavaco, A.-R., Panda, S., Dong, Y., Kuzmich, N., Lichtenstein, G., Peleg, Y., Harat, H., Jozwiak, A., Cai, J., Heinig, U., Meir, S., Rogachev, I., & Aharoni, A. (2024). The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction. Molecular Plant, 17(7), 1129–1150. https://doi.org/10.1016/j.molp.2024.05.012
Bonilla, J., Giannotti, G., Kregar, N. P., Heinsbroek, J. A., Olson, D. E., & Peters, J. (2024). The psychedelic drug DOI reduces heroin motivation by targeting 5-HT2A receptors in a heroin and alcohol co-use model. Neuropharmacology, 261, 110163. https://doi.org/10.1016/j.neuropharm.2024.110163
Brockett, A. T., & Francis, N. A. (2024). Psilocybin decreases neural responsiveness and increases functional connectivity while preserving pure-tone frequency selectivity in mouse auditory cortex. Journal of Neurophysiology, 132(1), 45–53. https://doi.org/10.1152/jn.00124.2024
Brownstien, M., Lazar, M., Botvinnik, A., Shevakh, C., Blakolmer, K., Lerer, L., Lifschytz, T., & Lerer, B. (2024). Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02786-0
Bryson, N., Alexander, R., Asnis-Alibozek, A., & Ehlers, M. D. (2024). RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy- N , N -diisopropyltryptamine. ACS Chemical Neuroscience, 15(12), 2386–2395. https://doi.org/10.1021/acschemneuro.4c00058
Chen, M., Ma, S., Liu, H., Dong, Y., Tang, J., Ni, Z., Tan, Y., Duan, C., Li, H., Huang, H., Li, Y., Cao, X., Lingle, C. J., Yang, Y., & Hu, H. (2024). Brain region–specific action of ketamine as a rapid antidepressant. Science, 385(6709), eado7010. https://doi.org/10.1126/science.ado7010
Conn, K., Milton, L. K., Huang, K., Munguba, H., Ruuska, J., Lemus, M. B., Greaves, E., Homman-Ludiye, J., Oldfield, B. J., & Foldi, C. J. (2024). Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: Contributions from 5-HT1A and 5-HT2A receptor mechanisms. Molecular Psychiatry, 29(10), 3291–3304. https://doi.org/10.1038/s41380-024-02575-9
Di Ianni, T., Ewbank, S. N., Levinstein, M. R., Azadian, M. M., Budinich, R. C., Michaelides, M., & Airan, R. D. (2024). Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats. Nature Communications, 15(1), 893. https://doi.org/10.1038/s41467-024-45157-7
Diniz, C. R. A. F., Crestani, A. P., Casarotto, P. C., Biojone, C., Cannarozzo, C., Winkel, F., Prozorov, M. A., Kot, E. F., Goncharuk, S. A., Benette Marques, D., Rakauskas Zacharias, L., Autio, H., Sahu, M. P., Borges-Assis, A. B., Leite, J. P., Mineev, K. S., Castrén, E., & Resstel, L. B. M. (2024). Fluoxetine and Ketamine Enhance Extinction Memory and Brain Plasticity by Triggering the p75 Neurotrophin Receptor Proteolytic Pathway. Biological psychiatry, S0006-3223(24)01425-2. Advance online publication. https://doi.org/10.1016/j.biopsych.2024.06.021
Duque, M., Chen, A. B., Hsu, E., Narayan, S., Rymbek, A., Begum, S., Saher, G., Cohen, A. E., Olson, D. E., Li, Y., Prober, D. A., Bergles, D. E., Fishman, M. C., Engert, F., & Ahrens, M. B. (2024). Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance. Neuron, 113(3), 426-443.e5. https://doi.org/10.1016/j.neuron.2024.11.011
Effinger, D. P., Hoffman, J. L., Mott, S. E., Magee, S. N., Quadir, S. G., Rollison, C. S., Toedt, D., Echeveste Sanchez, M., High, M. W., Hodge, C. W., & Herman, M. A. (2024). Increased reactivity of the paraventricular nucleus of the hypothalamus and decreased threat responding in male rats following psilocin administration. Nature Communications, 15(1), 5321. https://doi.org/10.1038/s41467-024-49741-9
Fan, L., Zhuang, Y., Wu, H., Li, H., Xu, Y., Wang, Y., He, L., Wang, S., Chen, Z., Cheng, J., Xu, H. E., & Wang, S. (2024). Structural basis of psychedelic LSD recognition at dopamine D1 receptor. Neuron, 112(19), 3295-3310.e8. https://doi.org/10.1016/j.neuron.2024.07.003
Farinha-Ferreira, M., Miranda-Lourenço, C., Galipeau, C., Lenkei, Z., & Sebastião, A. M. (2024). Concurrent stress modulates the acute and post-acute effects of psilocybin in a sex-dependent manner. Neuropharmacology, 110280. https://doi.org/10.1016/j.neuropharm.2024.110280
Fisher, E. L., Smith, R., Conn, K., Corcoran, A. W., Milton, L. K., Hohwy, J., & Foldi, C. J. (2024). Psilocybin increases optimistic engagement over time: Computational modelling of behaviour in rats. Translational Psychiatry, 14(1), 394. https://doi.org/10.1038/s41398-024-03103-7
Flanagan, T. W., Foster, T. P., Galbato, T. E., Lum, P. Y., Louie, B., Song, G., Halberstadt, A. L., Billac, G. B., & Nichols, C. D. (2024). Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression. ACS Pharmacology & Translational Science, 7(2), 478–492. https://doi.org/10.1021/acsptsci.3c00297
Fletcher, P. J., Li, Z., Ji, X. D., & Lê, A. D. (2024). Established sensitization of ethanol-induced locomotor activity is not reversed by psilocybin or the 5-HT2A receptor agonist TCB-2 in male DBA/2J mice. Pharmacology Biochemistry and Behavior, 235, 173703. https://doi.org/10.1016/j.pbb.2023.173703
Funk, D., Araujo, J., Slassi, M., Lanthier, J., Atkinson, J., Feng, D., Lau, W., Lê, A., & Higgins, G. A. (2024). Effect of a single psilocybin treatment on Fos protein expression in male rat brain. Neuroscience, 539, 1–11. https://doi.org/10.1016/j.neuroscience.2024.01.001
Gattuso, J. J., Wilson, C., Hannan, A. J., & Renoir, T. (2024). Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour. Neuropharmacology, 262, 110202. https://doi.org/10.1016/j.neuropharm.2024.110202
Glatfelter, G. C., Clark, A. A., Cavalco, N. G., Landavazo, A., Partilla, J. S., Naeem, M., Golen, J. A., Chadeayne, A. R., Manke, D. R., Blough, B. E., McCorvy, J. D., & Baumann, M. H. (2024). Serotonin 1A Receptors Modulate Serotonin 2A Receptor-Mediated Behavioral Effects of 5-Methoxy- N , N -dimethyltryptamine Analogs in Mice. ACS Chemical Neuroscience, 15(24), 4458–4477. https://doi.org/10.1021/acschemneuro.4c00513
Glatfelter, G. C., Pottie, E., Partilla, J. S., Stove, C. P., & Baumann, M. H. (2024). Comparative Pharmacological Effects of Lisuride and Lysergic Acid Diethylamide Revisited. ACS Pharmacology & Translational Science, 7(3), 641–653. https://doi.org/10.1021/acsptsci.3c00192
Gomes, I., Gupta, A., Margolis, E. B., Fricker, L. D., & Devi, L. A. (2024). Ketamine and Major Ketamine Metabolites Function as Allosteric Modulators of Opioid Receptors. Molecular Pharmacology, 106(5), 240–252. https://doi.org/10.1124/molpharm.124.000947
Harris-Blum, L., Smith, Z., Ortiz, R. J., Athreya, D., Chang, A., Kulkarni, P. P., & Ferris, C. F. (2024). Developmental changes in brain structure and function following exposure to oral LSD during adolescence. Scientific Reports, 14(1), 18632. https://doi.org/10.1038/s41598-024-69597-9
Havel, V., Kruegel, A. C., Bechand, B., McIntosh, S., Stallings, L., Hodges, A., Wulf, M. G., Nelson, M., Hunkele, A., Ansonoff, M., Pintar, J. E., Hwu, C., Ople, R. S., Abi-Gerges, N., Zaidi, S. A., Katritch, V., Yang, M., Javitch, J. A., Majumdar, S., … Sames, D. (2024). Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models. Nature Communications, 15(1), 8118. https://doi.org/10.1038/s41467-024-51856-y
Hibicke, M., Billac, G., & Nichols, C. D. (2024). Preadministration of Lorazepam Reduces Efficacy and Longevity of Antidepressant-Like Effect from a Psychedelic. Psychedelic Medicine, 2(1), 10–14. https://doi.org/10.1089/psymed.2023.0037
Jacobs, D. S., Bogachuk, A. P., Le Moing, C. L., & Moghaddam, B. (2024). Effects of psilocybin on uncertain punishment learning. Neurobiology of Learning and Memory, 213, 107954. https://doi.org/10.1016/j.nlm.2024.107954
Jayakodiarachchi, N., Maurer, M. A., Schultz, D. C., Dodd, C. J., Thompson Gray, A., Cho, H. P., Boutaud, O., Jones, C. K., Lindsley, C. W., & Bender, A. M. (2024). Evaluation of the Indazole Analogs of 5-MeO-DMT and Related Tryptamines as Serotonin Receptor 2 Agonists. ACS Medicinal Chemistry Letters, 15(2), 302–309. https://doi.org/10.1021/acsmedchemlett.3c00566
Jiang, C., DiLeone, R. J., Pittenger, C., & Duman, R. S. (2024). The endogenous opioid system in the medial prefrontal cortex mediates ketamine’s antidepressant-like actions. Translational Psychiatry, 14(1), 90. https://doi.org/10.1038/s41398-024-02796-0
Jiang, K., Zheng, Y., Zeng, L., Wang, L., Li, F., Pu, J., Lu, Y., Zhao, S., & Xu, F. (2024). The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules. Cell Reports, 43(7), 114505. https://doi.org/10.1016/j.celrep.2024.114505
Johnson, C. B., Walther, D., Baggott, M. J., Baker, L. E., & Baumann, M. H. (2024). Novel Benzofuran Derivatives Induce Monoamine Release and Substitute for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine. The Journal of Pharmacology and Experimental Therapeutics, 391(1), 22–29. https://doi.org/10.1124/jpet.123.001837
Jones, N. T., Wagner, L., Hahn, M. C. P., Scarlett, C. O., & Wenthur, C. J. (2024). In vivo validation of psilacetin as a prodrug yielding modestly lower peripheral psilocin exposure than psilocybin. Frontiers in Psychiatry, 14, 1303365. https://doi.org/10.3389/fpsyt.2023.1303365
Kelly, T. J., Bonniwell, E. M., Mu, L., Liu, X., Hu, Y., Friedman, V., Yu, H., Su, W., McCorvy, J. D., & Liu, Q. (2024). Psilocybin analog 4-OH-DiPT enhances fear extinction and GABAergic inhibition of principal neurons in the basolateral amygdala. Neuropsychopharmacology, 49(5), 854–863. https://doi.org/10.1038/s41386-023-01744-8
Kim, J.-W., Kleinfelter, B., Kavalali, E. T., & Monteggia, L. M. (2024). Distinct synaptic mechanisms drive the behavioral response to acute stress and rapid correction by ketamine. Neuropsychopharmacology, 49(12), 1916–1924. https://doi.org/10.1038/s41386-024-01908-0
Klein, A. K., Austin, E. W., Cunningham, M. J., Dvorak, D., Gatti, S., Hulls, S. K., Kiss, L., Kruegel, A. C., Marek, G. J., Papp, M., Sporn, J., & Hughes, Z. A. (2024). GM-1020: A novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents. Neuropsychopharmacology, 49(6), 905–914. https://doi.org/10.1038/s41386-023-01783-1
Kristiansen, K., Kroeze, W. K., Willins, D. L., Gelber, E. I., Savage, J. E., Glennon, R. A., & Roth, B. L. (2000). A Highly Conserved Aspartic Acid (Asp-155) Anchors the Terminal Amine Moiety of Tryptamines and Is Involved in Membrane Targeting of the 5-HT2A Serotonin Receptor But Does Not Participate in Activation via a “Salt-Bridge Disruption” Mechanism. The Journal of Pharmacology and Experimental Therapeutics, 293(3), 735–746. https://doi.org/10.1016/S0022-3565(24)39293-6
Krupp, K. T., Yaeger, J. D. W., Ledesma, L. J., Withanage, M. H. H., Gale, J. J., Howe, C. B., Allen, T. J., Sathyanesan, M., Newton, S. S., & Summers, C. H. (2024). Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress. Neuropharmacology, 252, 109949. https://doi.org/10.1016/j.neuropharm.2024.109949
Lauria, P. S. S., Gomes, J. D. M., Abreu, L. S., Santana, R. C., Nunes, V. L. C., Couto, R. D., Colavolpe, P. O., Silva, M. S. D., Soares, M. B. P., & Villarreal, C. F. (2024). Ayahuasca and its major component harmine promote antinociceptive effects in mouse models of acute and chronic pain. Journal of Ethnopharmacology, 323, 117710. https://doi.org/10.1016/j.jep.2024.117710
Lee, W.-L., Westergaard, X., Hwu, C., Hwu, J., Fiala, T., Lacefield, C., Boltaev, U., Mendieta, A. M., Lin, L., Sonders, M. S., Brown, K. R., He, K., Asher, W. B., Javitch, J. A., Sulzer, D., & Sames, D. (2024). Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain. Journal of the American Chemical Society.
Loan Nguyen, T. M., Guilloux, J. P., Defaix, C., Mendez-David, I., Etting, I., Alvarez, J. C., McGowan, J. C., Highland, J. N., Zanos, P., Lovett, J., Moaddel, R., Corruble, E., David, D. J., Gould, T. D., Denny, C. A., & Gardier, A. M. (2024). Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions. Neuropharmacology, 258, 110065. https://doi.org/10.1016/j.neuropharm.2024.110065
Looschen, K., Khatri, S. N., Maulik, M., Salisbury, C., Carman, A. F., Corriveau, K., Smith, C., Manetti, D., Romanelli, M. N., Arias, H. R., Gipson, C. D., & Mitra, S. (2024). Novel psychoplastogen DM506 reduces cue-induced heroin-seeking and inhibits tonic GABA currents in the Prelimbic Cortex. Neurochemistry International, 178, 105785. https://doi.org/10.1016/j.neuint.2024.105785
M. Ro̷rsted, E., Jensen, A. A., Smits, G., Frydenvang, K., & Kristensen, J. L. (2024). Discovery and Structure–Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists. Journal of Medicinal Chemistry, 67(9), 7224–7244. https://doi.org/10.1021/acs.jmedchem.4c00082
Ma, L., Eguchi, A., Liu, G., Qu, Y., Wan, X., Murayama, R., Mori, C., & Hashimoto, K. (2024). A role of gut–brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress. Pharmacology Biochemistry and Behavior, 238, 173736. https://doi.org/10.1016/j.pbb.2024.173736
Mantas, I., Flais, I., Masarapu, Y., Ionescu, T., Frapard, S., Jung, F., Le Merre, P., Saarinen, M., Tiklova, K., Salmani, B. Y., Gillberg, L., Zhang, X., Chergui, K., Carlén, M., Giacomello, S., Hengerer, B., Perlmann, T., & Svenningsson, P. (2024). Claustrum and dorsal endopiriform cortex complex cell-identity is determined by Nurr1 and regulates hallucinogenic-like states in mice. Nature Communications, 15(1), 8176. https://doi.org/10.1038/s41467-024-52429-9
Mastrodonato, A., Jin, M., Kee, N., Lanio, M., Tapia, J., Quintana, L., Muñoz Zamora, A., Deng, S. X., Xu, X., Landry, D. W., & Denny, C. A. (2024). Prophylactic (R,S)-ketamine and (2S,6S)-hydroxynorketamine Decrease Fear Expression by Differentially Modulating Fear Neural Ensembles. Biological psychiatry, S0006-3223(24)01649-4. Advance online publication. https://doi.org/10.1016/j.biopsych.2024.09.024
Muir, J., Lin, S., Aarrestad, I. K., Daniels, H. R., Ma, J., Tian, L., Olson, D. E., & Kim, C. K. (2024). Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states. Science, 386(6723), 802–810. https://doi.org/10.1126/science.adl0666
N. Costa, M., Goto-Silva, L., M. Nascimento, J., Domith, I., Karmirian, K., Feilding, A., Trindade, P., Martins-de-Souza, D., & K. Rehen, S. (2024). LSD Modulates Proteins Involved in Cell Proteostasis, Energy Metabolism and Neuroplasticity in Human Cerebral Organoids. ACS Omega, acsomega.4c04712. https://doi.org/10.1021/acsomega.4c04712
Nogueira, M., Ferreira Golbert, D. C., Menezes, R., Nóbrega De Almeida, R., Galvão-Coelho, N. L., Siroky, A. N., Lima, T. Z., Maia, H., Leão, K. E., & Leão, R. N. (2024). Serotonergic psychedelic 5-MeO-DMT alters plasticity-related gene expression and generates anxiolytic effects in stressed mice. Molecular Psychiatry, 30(1), 50–60. https://doi.org/10.1038/s41380-024-02655-w
Olejníková-Ladislavová, L., Fujáková-Lipski, M., Šíchová, K., Danda, H., Syrová, K., Horáček, J., & Páleníček, T. (2024). Mescaline-induced behavioral alterations are mediated by 5-HT2A and 5-HT2C receptors in rats. Pharmacology Biochemistry and Behavior, 245, 173903. https://doi.org/10.1016/j.pbb.2024.173903
Olson, R. J., Bartlett, L., Sonneborn, A., Milton, R., Bretton-Granatoor, Z., Firdous, A., Harris, A. Z., & Abbas, A. I. (2024). Decoupling of cortical activity from behavioral state following administration of the classic psychedelic DOI. Neuropharmacology, 257, 110030. https://doi.org/10.1016/j.neuropharm.2024.110030
Ornelas, I. M., Carrilho, B. D. S., Ventura, M. A. V. D. C., Domith, I., De V. Silveira, C. M., Dos Santos, V. F., Delou, J. M., Moll, F., Pereira, H. M. G., Junqueira, M., Aguilaniu, H., & Rehen, S. (2024). Lysergic acid diethylamide induces behavioral changes in Caenorhabditis elegans. Neuroscience Letters, 837, 137903. https://doi.org/10.1016/j.neulet.2024.137903
Palmisano, V. F., Agnorelli, C., Fagiolini, A., Erritzoe, D., Nutt, D., Faraji, S., & Nogueira, J. J. (2024). Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations. Biochemistry, acs.biochem.3c00598. https://doi.org/10.1021/acs.biochem.3c00598
Pazur, E. J., Kalatanova, A., Tasker, N. R., Vainionpää, K., Leinonen, H., & Wipf, P. (2024). Synthesis and Biological Analysis of Iso-dimethyltryptamines in a Model of Light-Induced Retinal Degeneration. ACS Medicinal Chemistry Letters, 15(7), 1049–1056. https://doi.org/10.1021/acsmedchemlett.4c00130
Piazza, M. K., Kavalali, E. T., & Monteggia, L. M. (2024). Ketamine induced synaptic plasticity operates independently of long-term potentiation. Neuropsychopharmacology, 49(11), 1758–1766. https://doi.org/10.1038/s41386-024-01895-2
Puigseslloses, P., Nadal-Gratacós, N., Ketsela, G., Weiss, N., Berzosa, X., Estrada-Tejedor, R., Islam, M. N., Holy, M., Niello, M., Pubill, D., Camarasa, J., Escubedo, E., Sitte, H. H., & López-Arnau, R. (2024). Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: Insights into psychoactive and thermoregulatory properties. Molecular Psychiatry, 29(8), 2346–2358. https://doi.org/10.1038/s41380-024-02506-8
Rakoczy, R. J., Runge, G. N., Sen, A. K., Sandoval, O., Wells, H. G., Nguyen, Q., Roberts, B. R., Sciortino, J. H., Gibbons, W. J., Friedberg, L. M., Jones, J. A., & McMurray, M. S. (2024). Pharmacological and behavioural effects of tryptamines present in psilocybin‐containing mushrooms. British Journal of Pharmacology, 181(19), 3627–3641. https://doi.org/10.1111/bph.16466
Rein, B., Raymond, K., Boustani, C., Tuy, S., Zhang, J., St. Laurent, R., Pomrenze, M. B., Boroon, P., Heifets, B., Smith, M., & Malenka, R. C. (2024). MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens. Science Advances, 10(17), eadl6554. https://doi.org/10.1126/sciadv.adl6554
Ren, W., Yu, S., Guo, K., Lu, C., & Zhang, Y. Q. (2024). Disrupted Human–Dog Interbrain Neural Coupling in Autism‐Associated Shank3 Mutant Dogs. Advanced Science, 11(41), 2402493. https://doi.org/10.1002/advs.202402493
Ribeiro, F. C., Cozachenco, D., Argyrousi, E. K., Staniszewski, A., Wiebe, S., Calixtro, J. D., Soares‐Neto, R., Al‐Chami, A., Sayegh, F. E., Bermudez, S., Arsenault, E., Cossenza, M., Lacaille, J., Nader, K., Sun, H., De Felice, F. G., Lourenco, M. V., Arancio, O., Aguilar‐Valles, A., … Ferreira, S. T. (2024). The ketamine metabolite ( 2R,6R )‐hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer’s disease. Alzheimer’s & Dementia, 20(8), 5398–5410. https://doi.org/10.1002/alz.14034
Šabanović, M., Lazari, A., Blanco-Pozo, M., Tisca, C., Tachrount, M., Martins-Bach, A. B., Lerch, J. P., Walton, M. E., & Bannerman, D. M. (2024). Lasting dynamic effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine ((±)-DOI) on cognitive flexibility. Molecular Psychiatry, 29(6), 1810–1823. https://doi.org/10.1038/s41380-024-02439-2
Saha Roy, D., Singh, A., Vaidya, V. A., Huster, D., Mote, K. R., & Maiti, S. (2024). Effects of a Serotonergic Psychedelic on the Lipid Bilayer. ACS Chemical Neuroscience, 15(21), 4066–4074. https://doi.org/10.1021/acschemneuro.4c00484
Sekssaoui, M., Bockaert, J., Marin, P., & Bécamel, C. (2024). Antidepressant-like effects of psychedelics in a chronic despair mouse model: Is the 5-HT2A receptor the unique player? Neuropsychopharmacology, 49(4), 747–756. https://doi.org/10.1038/s41386-024-01794-6
Shahar, O., Botvinnik, A., Shwartz, A., Lerer, E., Golding, P., Buko, A., Hamid, E., Kahn, D., Guralnick, M., Blakolmer, K., Wolf, G., Lotan, A., Lerer, L., Lerer, B., & Lifschytz, T. (2024). Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain. Molecular Psychiatry, 29(7), 2059–2073. https://doi.org/10.1038/s41380-024-02477-w
Shakir, J., Pedicini, M., Bullock, B. C., Hoen, P. W., Macias, L. K., Freiman, J., Pletnikov, M. V., Tamashiro, K. L. K., & Cordner, Z. A. (2024). Effects of psilocybin on body weight, body composition, and metabolites in male and female mice. Physiology & Behavior, 284, 114627. https://doi.org/10.1016/j.physbeh.2024.114627
Shaw, H. E., Patel, D. R., Gannon, B. M., Fitzgerald, L. R., Carbonaro, T. M., Johnson, C. R., & Fantegrossi, W. E. (2024). Phencyclidine-Like Abuse Liability and Psychosis-Like Neurocognitive Effects of Novel Arylcyclohexylamine Drugs of Abuse in Rodents. The Journal of Pharmacology and Experimental Therapeutics, 390(1), 14–28. https://doi.org/10.1124/jpet.123.001942
Sherwood, A. M., Burkhartzmeyer, E. K., Williamson, S. E., Baumann, M. H., & Glatfelter, G. C. (2024). Psychedelic-like Activity of Norpsilocin Analogues. ACS Chemical Neuroscience, 15(2), 315–327. https://doi.org/10.1021/acschemneuro.3c00610
Soares, B. A., Yempala, T., Martínez-Afani, D., Acevedo-Fuentes, W., Brea, J., Loza, M. I., Cimadevila, M., & Cassels, B. K. (2024). Effect of Bulky N -Dibenzofuranylmethyl Substitution on the 5-HT2 Receptor Affinity and Efficacy of a Psychedelic Phenethylamine. ACS Chemical Neuroscience, 15(3), 608–616. https://doi.org/10.1021/acschemneuro.3c00639
Tae, H. S., Ortells, M. O., Yousuf, A., Xu, S. Q., Akk, G., Adams, D. J., & Arias, H. R. (2024). Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABAA receptor and CaV2.2 channel. Biochemical pharmacology, 223, 116183. https://doi.org/10.1016/j.bcp.2024.116183
Urbina, F., Jones, T., Harris, J. S., Snyder, S. H., Lane, T. R., & Ekins, S. (2024). Predicting the Hallucinogenic Potential of Molecules Using Artificial Intelligence. ACS Chemical Neuroscience, 15(16), 3078–3089. https://doi.org/10.1021/acschemneuro.4c00405
Varley, T. F., Havert, D., Fosque, L., Alipour, A., Weerawongphrom, N., Naganobori, H., O’Shea, L., Pope, M., & Beggs, J. (2024). The serotonergic psychedelic N,N-dipropyltryptamine alters information-processing dynamics in in vitro cortical neural circuits. Network Neuroscience, 8(4), 1421–1438. https://doi.org/10.1162/netn_a_00408
Varty, G. B., Canal, C. E., Mueller, T. A., Hartsel, J. A., Tyagi, R., Avery, K., Morgan, M. E., Reichelt, A. C., Pathare, P., Stang, E., Palfreyman, M. G., & Nivorozhkin, A. (2024). Synthesis and Structure–Activity Relationships of 2,5-Dimethoxy-4-Substituted Phenethylamines and the Discovery of CYB210010: A Potent, Orally Bioavailable and Long-Acting Serotonin 5-HT2 Receptor Agonist. Journal of Medicinal Chemistry, 67(8), 6144–6188. https://doi.org/10.1021/acs.jmedchem.3c01961
Vu, M. O., Butters, B. M., Canal, C. E., & Figueroa, X. A. (2024). Defined radio wave frequencies attenuate the head-twitch response in mice elicited by (±)-2,5-dimethoxy-4-iodoamphetamine. Electromagnetic Biology and Medicine, 43(4), 328–336. https://doi.org/10.1080/15368378.2024.2418552
Warren, H. T., Saeger, H. N., Tombari, R. J., Chytil, M., Rasmussen, K., & Olson, David. E. (2024). Psychoplastogenic DYRK1A Inhibitors with Therapeutic Effects Relevant to Alzheimer’s Disease. Journal of Medicinal Chemistry, 67(9), 6922–6937. https://doi.org/10.1021/acs.jmedchem.3c01696
Witowski, C. G., Hess, M. R., Jones, N. T., Pellitteri Hahn, M. C., Razidlo, J., Bhavsar, R., Beer, C., Gonzalez-Velazquez, N., Scarlett, C. O., Wenthur, C. J., & Von Salm, J. L. (2024). Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT). European Journal of Pharmaceutical Sciences, 199, 106803. https://doi.org/10.1016/j.ejps.2024.106803
Yang, C., Ali, T., Li, A., Gao, R., Yu, X., Li, S., & Li, T. (2024). Ketamine reverses chronic corticosterone-induced behavioral deficits and hippocampal synaptic dysfunction by regulating eIF4E/BDNF signaling. Neuropharmacology, 261, 110156. https://doi.org/10.1016/j.neuropharm.2024.110156
Yu, S.-J., Wu, K.-J., Wang, Y.-S., Bae, E., Chianelli, F., Bambakidis, N., & Wang, Y. (2024). Neuroprotective effects of psilocybin in a rat model of stroke. BMC Neuroscience, 25(1), 49. https://doi.org/10.1186/s12868-024-00903-x
Zahid, Z., Sultan, Z. W., Krause, B. M., Wenthur, C. J., Pearce, R. A., & Banks, M. I. (2024). Divergent Effects of Ketamine and the Serotoninergic Psychedelic 2,5-Dimethoxy-4-Iodoamphetamine on Hippocampal Plasticity and Metaplasticity. Psychedelic Medicine, 2(3), 166–177. https://doi.org/10.1089/psymed.2023.0061
Zhang, R., Anguiano, M., Aarrestad, I. K., Lin, S., Chandra, J., Vadde, S. S., Olson, D. E., & Kim, C. K. (2024). Rapid, biochemical tagging of cellular activity history in vivo. Nature Methods, 21(9), 1725–1735. https://doi.org/10.1038/s41592-024-02375-7
Zhao, X., Du, Y., Yao, Y., Dai, W., Yin, Y., Wang, G., Li, Y., & Zhang, L. (2024). Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice. Journal of Psychopharmacology, 38(5), 489–499. https://doi.org/10.1177/02698811241249436
Editorial / Commentary / Perspectives
Alpert, M. D., O’Donnell, K. C., Paleos, C. A., Sola, E., Stauffer, C. S., Wagner, A. C., Nicholas, C. R., & Mithoefer, M. C. (2024). Psychotherapy in Psychedelic Treatment: Safe, Evidence-Based, and Necessary. American Journal of Psychiatry, 181(1), 76–77. https://doi.org/10.1176/appi.ajp.20230665
“A diverse series of thoughtful and often impassioned arguments against active efforts to minimize or excise entirely — both theoretically and practically — the psychosocial component (or so-called “psychotherapy component”) of psychedelic therapy.” – CJ Healy (also responding to other Goodwin et al. replies)
“PAT, PAP, PT…there is yet to be consensus on language for psychedelic treatments in development. This lack of alignment has resulted in the role of psychotherapy being an increasingly contentious issue for many stakeholders. Valid arguments have been made regarding the role of psychotherapy in potentially FDA-approved psychedelic treatments. No one company, organization, or stakeholder group should be responsible for establishing best practices – a coordinated approach is required to support the entire industry. The opportunity is ripe for psychology to enter the chat. As experts continue to make valid and at times conflicting arguments, perhaps the conversation should evolve to identify who might “own” the psychotherapy of it all. There are highly qualified therapists with hundreds and thousands of hours of experience in psychedelic clinical trials confused about what their roles in real-world settings will be should products come to market. Isn’t everyone in this space confused about what their roles will be in the future? After all, this has never been done at commercial scale in the U.S. medical system. In an incipient and diverse industry might the current debate be missing the forest for the trees?
In December 2024 The American Psychiatric Association (APA) published updated practice guidelines on the treatment of Borderline Personality Disorder (BPD). The APA recommendation is tiered to include both psychosocial interventions and pharmacotherapy treatments. Importantly, they suggest that patients with BPD treated with “any psychotropic medication be time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.” Of note for emerging psychedelic treatments the APA does not distinguish between the numerous types of psychosocial interventions available; rather, the APA calls for a structured approach to psychotherapy, recognizing that many effective evidence-based options exist. Other examples of treatment models involving psychosocial interventions provide additional food for thought e.g. – SUD, HIV, bariatric surgery, dialysis, etc.
If the ultimate goal for those pursuing FDA approval is to provide treatment options that are safe and more effective than those presently available, shouldn’t the through line be meeting patients’ needs? Are we asking what patients want and incorporating that into decision-making or are we leaning into biased assumptions? All of the papers focused on this topic have provided space for healthy and much needed reflection and research.” – Gretchen Shaub (also responding to Weintraub et al. and Aday et al.)
Andrews, C. M., Hall, W., Humphreys, K., & Marsden, J. (2024). Crafting effective regulatory policies for psychedelics: What can be learned from the case of cannabis? Addiction, 120(2), 201–206. https://doi.org/10.1111/add.16575
“Andrews et al. note that early efforts with cannabis involved misrepresentation of medical use through “poorly-evidenced therapeutic claims”. A lack of movement at the federal level resulted in a disjointed regulatory policy landscape at the state and local levels – history is repeating itself in the psychedelic space. States lack the rigorous safety and efficacy data needed to develop appropriate regulatory policies for access to psychedelics. The cannabis access playbook seems to be copied and pasted with little regard for potential long-term impacts. The authors outline five pivotal considerations including challenges setting limits on potency and dosing with little safety data available, setting limits on advertising, packaging, warning labels, and how to handle false claims, the need for investment in public education, coordinated federal and state policies, and tax implications. For those pursuing FDA approval, many of these issues are solved for within the existing highly regulated medical model. Non-medical access pathways at the state and local levels may suffer from replicating piecemeal strategies – a concerted effort to separate access pathways is needed for all to succeed.” – Gretchen Shaub
Bogenschutz M. P. (2024). Pharmacological and Nonpharmacological Components of Psychedelic Treatments: The Whole is Not the Sum of the Parts. The American journal of psychiatry, 181(1), 75. https://doi.org/10.1176/appi.ajp.20230643
“A diverse series of thoughtful and often impassioned arguments against active efforts to minimize or excise entirely — both theoretically and practically — the psychosocial component (or so-called “psychotherapy component”) of psychedelic therapy.” – CJ Healy (also responding to other Goodwin et al. replies)
Colloca, L., & Fava, M. (2024). What should constitute a control condition in psychedelic drug trials? Nature Mental Health, 2(10), 1152–1160. https://doi.org/10.1038/s44220-024-00321-2
“Colloca and Fava explore the neurobiology of placebo and expectation effects, highlighting the longstanding methodological challenge of blinding in psychedelic trials. A key strength of the article is its structured presentation of trial designs aimed at managing expectancy effects and minimizing bias, including the balanced placebo, sequential parallel comparison, and overt–covert administration designs; each with their strengths and limitations. Epistemologically, the authors appear to operate within an additive model rooted in isolating drug effects from contextual influences. This is particularly evident in their proposal to use virtual reality to disentangle the “phenomenology of psychedelics” from their “pharmacological effects” – an idea that risks reinforcing an outdated mind–brain dualism. For the field to move forward, we may need to acknowledge the complex and interactive nature of psychedelic therapy. The challenge, of course, is to design trials that reflect this complexity; but a preprint by Muthukumaraswamy et al. (2025) suggests there might be a way.” – Chloé Pronovost-Morgan
Deckel, G. M., Lepow, L. A., & Guss, J. (2024). “Psychedelic Assisted Therapy” Must Not Be Retired. American Journal of Psychiatry, 181(1), 77–78. https://doi.org/10.1176/appi.ajp.20230667
“The late Dr. Garret Deckel was an outstanding clinician and thinker, and she is surely missed by all of us who knew her. She and co-authors Dr. Lauren Lepow and Dr. Jeffrey Guss have made a critical point in this letter that is too easily forgotten: not all patients receiving psychedelic therapy are the same. While efforts to strip psychedelic-assisted therapy of its therapy in clinical settings could work for some people, it may be unethical and even dangerous to do so for those who are most vulnerable and at increased risk for adverse psychological outcomes.” – David Mathai
“A diverse series of thoughtful and often impassioned arguments against active efforts to minimize or excise entirely — both theoretically and practically — the psychosocial component (or so-called “psychotherapy component”) of psychedelic therapy.” – CJ Healy (also responding to other Goodwin et al. replies)
Earleywine, M., De Leo, J., Bhayana, D., Rajanna, B., & Scott, K. (2024). Psilocybin Without Psychotherapy: A Cart Without a Horse? The American journal of psychiatry, 181(1), 78–79. https://doi.org/10.1176/appi.ajp.20230572
“A diverse series of thoughtful and often impassioned arguments against active efforts to minimize or excise entirely — both theoretically and practically — the psychosocial component (or so-called “psychotherapy component”) of psychedelic therapy.” – CJ Healy (also responding to other Goodwin et al. replies)
Hanshaw, B. D., Fusunyan, M., Anderson, C. T. M., & Turban, J. L. (2024). Psychedelic-assisted therapy among sexual and gender minority communities. Nature Mental Health, 2(6), 636–644. https://doi.org/10.1038/s44220-024-00252-y
“Non-white, non-Western individuals with low incomes and educational levels from Global South countries are virtually absent from psychedelic research, resulting in significant biases. In this important article, the authors emphasize that this lack of diversity also affects sexual and gender minorities. These groups are particularly exposed to mental health issues caused by contemporary society’s oppressive and stigmatizing practices. The “minority stress theory” is a concept derived from this observation, referring to the specific experiences of these populations. To date, however, no clinical study has attempted to investigate the impact of psychedelic use on alleviating this particular stress. The authors express surprise that, “With nearly 21% of Generation Z identifying within the sexual and gender minority community, this is a notable gap in the psychedelic research landscape”. They note that two explanatory models for the action of psychedelics—the REBUS model and the CANAL model—can readily incorporate an analysis of the “minority stress” experience, which would allow for a better understanding of the therapeutic effects in this specific indication.” – Zoë Dubus
Jacobs, E., Earp, B. D., Appelbaum, P. S., Bruce, L., Cassidy, K., Celidwen, Y., Cheung, K., Clancy, S. K., Devenot, N., Evans, J., Lynch, H. F., Friesen, P., Romeu, A. G., Gehani, N., Maloof, M., Marcus, O., Martin Moen, O., Mertens, M., Nayak, S. M., … Yaden, D. B. (2024). The Hopkins-Oxford Psychedelics Ethics (HOPE) Working Group Consensus Statement. The American Journal of Bioethics, 24(7), 6–12. https://doi.org/10.1080/15265161.2024.2342764
“The HOPE Consensus Statement is an offering from a group of 32 stakeholders— Indigenous scholars, psychiatrists, ethicists, psychedelic scientists, anthropologists, philosophers, and harm reduction specialists—convened to develop a shared understanding of ethical practice with psychedelics. The need for developing an ethics of psychedelics is crucial given the field’s history of serious transgressions—including MK Ultra experiments, abuses of patients and prisoners, sexual boundary violations by guides, and appropriative practices toward Indigenous communities—transgressions that regrettably are not confined to the distant past.
At four pages, the statement is deliberately minimal, offering a common orientation rather than exhaustive guidance. Many complex issues, such as the ethics of therapeutic touch during psychedelic experiences, will require considerable collaborative work among patients, practitioners, and ethicists.
For me, it was particularly important that the statement recognise that psychedelic ethics extends beyond medical contexts. Though clinical applications dominate headlines, the majority of psychedelic use always has, and always will, occur outside medical settings, including for spiritual, self-development, and recreational purposes. Such use is just as worthy of care and thoughtful attention, and we need ethical frameworks that look beyond the clinical, acknowledging the broader societal currents that psychedelic use is situated in.
The HOPE statement represents only a beginning in the conveners’ intention to better establish psychedelic ethics as a field of inquiry. Ethics is a conversation everyone has a stake in, not something to be agreed by 32 people. That’s why we were pleased to host an August summit for 200 people in Washington, D.C., expanding the conversation to include more diverse voices. But neither is ethics the preserve of academic and clinical circles, which is why we’ve made efforts to make the statement accessible—translating it into six languages to reach beyond traditional spheres of influence.” – Eddie Jacobs
Lemarchand, C., Chopin, R., Paul, M., Braillon, A., Cosgrove, L., Cristea, I., Fried, E. I., Turner, E. H., & Naudet, F. (2024). Fragile promise of psychedelics in psychiatry. BMJ (Clinical research ed.), 387, e080391. https://doi.org/10.1136/bmj-2024-080391
“Alongside the overly positive, and in many places highly repetitive, reviews on psychedelic medicine, there has been an emergence of more critical points of view, of which the analysis/opinion by Cédric Lemarchand and others is a great example. I, for one, welcome the more sceptical and wary approaches to the field where e.g. the poor experimental designs and small numbers of participants are properly acknowledged. Studies with psychedelics also pose problems to the tradition of clinical investigation, especially in controlling blinding and expectations, and I think addressing these will be of utmost importance, but also something that should then be applied to clinical (psycho)pharmacological studies in large.” – Lauri Elsilä
McInnes, L. A., Marton, T. F., & Qian, J. J. (2024). Embracing pragmatism for ketamine insurance coverage: Leveraging real-world evidence. Journal of Affective Disorders, 352, 199–200. https://doi.org/10.1016/j.jad.2024.02.033
“In recent years, regulatory bodies like the FDA have been increasingly open to using real world evidence (RWE) to support new indications for approved drugs. RCTs remain a gold standard for establishing efficacy, but results may not be generalizable to more complex patients in community care settings, as opposed to controlled research populations and environments. A shift in the medical community towards embracing RWE could help move the needle on coverage of novel treatments with payors. Our current complex healthcare delivery environment necessitates innovative tactics.
The authors cite a recent review of evidence for ketamine infusion therapy (KIT), suggesting RWE could be leveraged for KIT insurance coverage. As a strength, they note the data on KIT effect size are quite consistent. But, significant amounts of missing data, which could lead to inflated effect size estimates, is a limitation, as are lack of demographic information and placebo control. There is also likely to be bias toward higher patient socioeconomic status given the out-of-pocket cost of KIT, and less diversity than a clinical trial which might seek to address inclusivity as an aim.
Since ketamine is off-patent, there is little financial incentive for any company to pursue FDA-registered trials to support a label for depression, making RWE even more relevant. RWE can increase access to KIT if it is packaged in such a way as to increase willingness towards reimbursement by payers. Efforts have been made to synthesize health records and claims data for presentation to CMS, and with a few recent local Medicaid wins, there is a clear opportunity to continue this trend, perhaps even bringing private payors along in the near future. This is a faster and less expensive pathway than interventional studies, and payors can feel confident in this approach, given FDA’s publication of a Framework, as well as prior approvals of label expansions in other therapeutic areas using RWE.
The pragmatic call to action here is: ketamine attributes present a unique opportunity to capitalize on existing safety, effectiveness, and cost-effectiveness data. A public benefit approach when pharma profit isn’t possible presents ripe conditions for transforming innovative treatment option access for the world’s 3rd leading cause of disability.” – Hailey Gilmore
Mian, M. N., Dinh, M. T., Coker, A. R., Mitchell, J. M., & Anderson, B. T. (2024). Psychedelic Regulation Beyond the Controlled Substances Act: A Three-Dimensional Framework for Characterizing Policy Options. The American journal of psychiatry, 182(1), 6–9. https://doi.org/10.1176/appi.ajp.20230787
“Mian et al.’s 3D framework is a refreshing and much-needed addition to the U.S. psychedelic policy dialogue. By defining the legality, therapeutic intent, and structure of psychedelics, the authors articulate the context for psychedelics across critical domains and subdimensions that often get lost in translation within and among various stakeholder groups. This 3D framework is timely, especially with an increased need to define various efforts for legal access. FDA-regulated medical use is wholly different from state-level use and there are valid arguments for defining, separating, and protecting individual efforts. Ultimately, policymakers need support as they are tasked with ensuring access to medical use and creating regulations for safe non-medical use. The goal of these multidimensional frameworks is to develop sound, evidence-based public health campaigns that drive risk mitigation and improve public safety regardless of access pathway. The Controlled Substances Act indeed impacts all efforts, some more acutely than others – hopefully, this work helps decision makers understand this critical access lever. This work creates a path forward for productive policy development in a nebulous space.” – Gretchen Shaub
Newson, M., Haslam, S. A., Haslam, C., Cruwys, T., & Roseman, L. (2024). Social identity processes as a vehicle for therapeutic success in psychedelic treatment. Nature Mental Health, 2(9), 1010–1017. https://doi.org/10.1038/s44220-024-00302-5
“The authors highlight not just the general influence of the immediate social environment on a psychedelic experience but also the specific influence of having a psychedelic experience as part of a group and the potential unique therapeutic benefits that might be gained from using psychedelics in group settings.” – CJ Healy
O’Donnell, K. C., Anderson, B. T., Barrett, F. S., Bogenschutz, M. P., Grob, C. S., Hendricks, P. S., Kelmendi, B., Nayak, S. M., Nicholas, C. R., Paleos, C. A., Stauffer, C. S., & Gukasyan, N. (2024). Misinterpretations and Omissions: A Critical Response to Goodwin and Colleagues’ Commentary on Psilocybin-Assisted Therapy. American Journal of Psychiatry, 181(1), 74–75. https://doi.org/10.1176/appi.ajp.20230661
“A diverse series of thoughtful and often impassioned arguments against active efforts to minimize or excise entirely — both theoretically and practically — the psychosocial component (or so-called “psychotherapy component”) of psychedelic therapy.” – CJ Healy (also responding to other Goodwin et al. replies)
Ostrovsky, A., & Barnett, B. S. (2024). New Billing Codes Offer Opportunity to Investigate Psychedelic Treatment. Psychedelic Medicine, 2(3), 184–186. https://doi.org/10.1089/psymed.2023.0071
“This piece is a call to action for medical model stakeholders – systems change is arduous, slow, and necessitates informed coalition development. Despite enormous efforts by drug development companies seeking FDA approval for psychedelic treatments, uptake has been sluggish. In June 2024 the American Medical Association (AMA) approved the Category III CPT codes for ‘‘Continuous In-Person Monitoring and Intervention During Psychedelic Medication Therapy’’ (0820T, 0821T, and 0822T); these codes were created to capture the work of qualified healthcare professionals responsible for psychosocial interventions during the drug administration of novel psychedelic treatments. Adequate CPT I codes exist for the psychosocial interventions that occur during preparation and integration sessions.
CPT III codes are temporary research tools that expire after five years if not used or deliberately extended; these codes (0820T, 0821T, and 0822T) are due to sunset in 2028. Albeit an exceptional and historic effort, the ultimate success of these codes is in their adoption and evaluation to inform the conversion to permanent CPT I codes. There is much work to be done in coordination with manufacturers, health systems, coding professionals, professional societies, and agencies of jurisdiction to ensure effective implementation and adoption of these codes. The full extent of the workforce needed for the implementation of psychedelic treatments in the U.S. healthcare system is unknown – these data are a vital piece of the puzzle we are attempting to solve. These codes must be used so that we can start to answer product and indication agnostic questions like, who is doing what work, at what degree of input, what should the pay scale be for emerging qualified HCPs during administration, etc.? There are helpful examples across the practice of medicine to help inform sustainable policy solutions that ensure professionals doing the work are appropriately compensated. As Ostrovsky and Barnett layout in this paper – adopt these codes to support critical implementation research.” – Gretchen Shaub
Schenberg, E. E., King, F., 4th, da Fonseca, J. E., & Roseman, L. (2024). Is Poorly Assisted Psilocybin Treatment an Increasing Risk? The American journal of psychiatry, 181(1), 75–76. https://doi.org/10.1176/appi.ajp.20230664
“A diverse series of thoughtful and often impassioned arguments against active efforts to minimize or excise entirely — both theoretically and practically — the psychosocial component (or so-called “psychotherapy component”) of psychedelic therapy.” – CJ Healy (also responding to other Goodwin et al. replies)
Weintraub, M. J., & Miklowitz, D. J. (2024). How should psychotherapy proceed when adjoined with psychedelics? World Psychiatry, 23(1), 157–158. https://doi.org/10.1002/wps.21170
“PAT, PAP, PT…there is yet to be consensus on language for psychedelic treatments in development. This lack of alignment has resulted in the role of psychotherapy being an increasingly contentious issue for many stakeholders. Valid arguments have been made regarding the role of psychotherapy in potentially FDA-approved psychedelic treatments. No one company, organization, or stakeholder group should be responsible for establishing best practices – a coordinated approach is required to support the entire industry. The opportunity is ripe for psychology to enter the chat. As experts continue to make valid and at times conflicting arguments, perhaps the conversation should evolve to identify who might “own” the psychotherapy of it all. There are highly qualified therapists with hundreds and thousands of hours of experience in psychedelic clinical trials confused about what their roles in real-world settings will be should products come to market. Isn’t everyone in this space confused about what their roles will be in the future? After all, this has never been done at commercial scale in the U.S. medical system. In an incipient and diverse industry might the current debate be missing the forest for the trees?
In December 2024 The American Psychiatric Association (APA) published updated practice guidelines on the treatment of Borderline Personality Disorder (BPD). The APA recommendation is tiered to include both psychosocial interventions and pharmacotherapy treatments. Importantly, they suggest that patients with BPD treated with “any psychotropic medication be time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.” Of note for emerging psychedelic treatments the APA does not distinguish between the numerous types of psychosocial interventions available; rather, the APA calls for a structured approach to psychotherapy, recognizing that many effective evidence-based options exist. Other examples of treatment models involving psychosocial interventions provide additional food for thought e.g. – SUD, HIV, bariatric surgery, dialysis, etc.
If the ultimate goal for those pursuing FDA approval is to provide treatment options that are safe and more effective than those presently available, shouldn’t the through line be meeting patients’ needs? Are we asking what patients want and incorporating that into decision-making or are we leaning into biased assumptions? All of the papers focused on this topic have provided space for healthy and much needed reflection and research.” – Gretchen Shaub (also responding to Aday et al. and Alpert et al.)
Wolfgang, A. S., McClair, V. L., Schnurr, P. P., Holtzheimer, P. E., Woolley, J. D., Stauffer, C. S., Wolf, R. C., States, L. J., Benedek, D. M., Capaldi, V. F., Bradley, J., Fuller, M. A., Smyth, M. J., Hermes, E. D. A., Tenhula, W., & Wiechers, I. R. (2024). Research and Implementation of Psychedelic-Assisted Therapy in the Veterans Health Administration. The American journal of psychiatry, 182(1), 17–20. https://doi.org/10.1176/appi.ajp.20240751
“Wolfgang et al.’s report outlines important details behind essential work within the Department of Veterans Affairs to move potentially FDA-approved psychedelic treatments forward. The convening of the “State of the Art (SOTA) Conference: Psychedelic Treatments for Mental Health Conditions” in 2023 successfully created four workgroups to tackle complex issue areas. This tactical approach resulted in successful dedicated funding for continued research as well as the inception of an Integrated Project Team (IPT) consisting of diverse experts to focus on forward-looking planning for future research and implementation. There is an enormous need for collaboration across industry and agencies to adapt clinical development to infrastructure and implementation development. In a nascent area it is often a challenge to create space for future planning – there is always pressure to focus on immediate, short-term work. The establishment of SOTA and resulting efforts are an important step forward. This report adeptly shares the learnings and the need to educate on the multi-layered approaches necessary across diverse stakeholders in order to develop a sustainable and dynamic industry that keeps patients as the focal point.” – Gretchen Shaub
The above publications received comments from the researchers we surveyed. Here are further 2024 publications that Michael included in his list.
***
Aaronson, S. T., & Kozak, Z. (2024). New evidence for flexible psilocybin dosing in patients with treatment-resistant depression. Med, 5(3), 187–189. https://doi.org/10.1016/j.medj.2024.01.014
Aicher, H. D., Wolff, M., & Herwig, U. (2024). Psychedelic therapy – refining the claim of a paradigm shift. International Review of Psychiatry, 1–8. https://doi.org/10.1080/09540261.2024.2410853
Anderson, K., Elf, P., & Isham, A. (2024). Psychedelics as a tool for a more connected and sustainable world? Considering the importance of rituals, boundaries, and commitment. International Journal of Drug Policy, 133, 104571. https://doi.org/10.1016/j.drugpo.2024.104571
Appelbaum, P. S. (2024). Informed Consent to Psychedelic Treatment—A Work in Progress. JAMA Psychiatry, 81(6), 543. https://doi.org/10.1001/jamapsychiatry.2024.0124
Barksdale, B. R., Doss, M. K., Fonzo, G. A., & Nemeroff, C. B. (2024). The mechanistic divide in psychedelic neuroscience: An unbridgeable gap? Neurotherapeutics, 21(2), e00322. https://doi.org/10.1016/j.neurot.2024.e00322
Black, J. C., Monte, A. A., Dasgupta, N., Jewell, J. S., Rockhill, K. M., Olson, R. A., & Dart, R. C. (2024). Optimizing real-world benefit and risk of new psychedelic medications: The need for innovative postmarket surveillance. Nature Mental Health, 2(5), 469–477. https://doi.org/10.1038/s44220-024-00233-1
Brunello, C. A., Cannarozzo, C., & Castrén, E. (2024). Rethinking the role of TRKB in the action of antidepressants and psychedelics. Trends in Neurosciences, 47(11), 865–874. https://doi.org/10.1016/j.tins.2024.08.011
Butlen-Ducuing, F., Silva, F., Silva, I., Balabanov, P., & Thirstrup, S. (2024). Applying the EU regulatory framework for the clinical use of psychedelics. The Lancet Psychiatry, 12(1), 7–9. https://doi.org/10.1016/S2215-0366(24)00203-7
Cheung, K., Ehrenkranz, R., Hinkle, J. T., & Yaden, D. B. (2024). Commentary: A framework for assessment of adverse events in psychedelic research. Journal of Psychopharmacology, 02698811241309623. https://doi.org/10.1177/02698811241309623
Ching, T. H. W., & Shnayder, S. (2024). Capturing Synergy Holistically in Psychedelic Clinical Trials: Assessing Processes in Addition to Outcomes. Clinical Pharmacology & Therapeutics, 115(3), 400–400. https://doi.org/10.1002/cpt.3129
Cho, M., Rosenbaum, D., Schneider, E., & Hales, S. (2024). Letter to the Editor: Will Psilocybin-Assisted Therapy Reduce the Incidence of Medical Assistance in Dying? Journal of palliative medicine, 27(2), 158–159. https://doi.org/10.1089/jpm.2023.0668
Cristea, I. A., Cuijpers, P., & Halvorsen, J. Ø. (2024). The Psychotherapy in MDMA-Assisted Psychotherapy. JAMA Psychiatry, 81(11), 1053. https://doi.org/10.1001/jamapsychiatry.2024.2887
Dart, R. C. (2024). Can mind-altering prescription medicines be safe? Lessons from ketamine and esketamine. Clinical Toxicology, 62(8), 477–482. https://doi.org/10.1080/15563650.2024.2380773
DellaCrosse, M. A., Garcia-Romeu, A., & Davis, A. K. (2024). Seeing the forest for the trees: An ecological systems theory approach to addressing emergent issues in psychedelic-assisted therapy research. Journal of Psychedelic Studies. https://doi.org/10.1556/2054.2024.00374
Denomme, N., & Heifets, B. D. (2024). Ketamine, the First Associative Anesthetic? Some Considerations on Classifying Psychedelics, Entactogens, and Dissociatives. American Journal of Psychiatry, 181(9), 784–786. https://doi.org/10.1176/appi.ajp.20240644
Dhaliwal, O. M., Bobak, L., & Barnett, B. S. (2024). Ensuring Access to Psychedelic-Assisted Therapy in Rural Communities. Psychedelic Medicine, psymed.2024.0018. https://doi.org/10.1089/psymed.2024.0018
Ehrenkranz, R., Agrawal, M., Nayak, S. M., & Yaden, D. B. (2024). Adverse Events Should Not Be Surprising in Psychedelic Research. Psychedelic Medicine, psymed.2024.0006. https://doi.org/10.1089/psymed.2024.0006
Fried, E. I., Cristea, I. A., & Naudet, F. (2024). Treating Bipolar Depression Using Psilocybin—Validity Threats Regarding Efficacy and Safety. JAMA Psychiatry, 81(6), 633. https://doi.org/10.1001/jamapsychiatry.2024.0420
Golafshani, M., Buchman, D. Z., & Husain, M. I. (2024). Disability rights and experiential use of psychedelics in clinical research and practice. Npj Mental Health Research, 3(1), 34. https://doi.org/10.1038/s44184-024-00065-y
Gomes, S. P., Lima, S. R., Souza, F. G. D. M., & Bisol, L. W. (2024). Navigating the challenge of patient selection and scales to measure outcomes in ketamine trials for treatment-resistant depression. Journal of Psychopharmacology, 39(1), 76–78. https://doi.org/10.1177/02698811241276505
Goodwin, G. M., Malievskaia, E., Fonzo, G. A., & Nemeroff, C. B. (2024). Psychological Support for Psilocybin Treatment: Reply to Letters on Our Commentary. American Journal of Psychiatry, 181(1), 79–81. https://doi.org/10.1176/appi.ajp.20230905
Hartogsohn, I. (2024). A media ecology perspective on psychedelics. Explorations in Media Ecology, 23(1), 5–11. https://doi.org/10.1386/eme_00188_1
Heller, N. H., & Barrett, F. S. (2024). Teaching a new dog old tricks: Bringing rigor, grounding, and specificity to psychedelic neuropsychopharmacology. Neuropsychopharmacology, 50(1), 324–325. https://doi.org/10.1038/s41386-024-01954-8
Horwitz, R. I., Baker, J. B., & Cullen, M. R. (2024). Patient expectations are a feature of treatment strategy rather than a source of bias. PLOS Mental Health, 1(4), e0000115. https://doi.org/10.1371/journal.pmen.0000115
Jeffrey, J. K., Weintraub, M. J., & Grob, C. S. (2024). Clinical Research Trials of Psychedelic-Assisted Therapy in Adolescents Aged 16 to 17 Years: Rationale Balanced With Caution. Journal of the American Academy of Child & Adolescent Psychiatry, 63(12), 1196–1198. https://doi.org/10.1016/j.jaac.2024.03.021
Jelen, L. A., McShane, R., & Young, A. H. (2024). Guidelines for ketamine use in clinical psychiatry practice. BJPsych Open, 10(3), e107. https://doi.org/10.1192/bjo.2024.62
Johnson, D. E., & Rosenblat, J. D. (2024). Psilocybin-assisted psychotherapy as an ‘anti-distressant’ with multidimensional properties. Nature Mental Health, 2(11), 1275–1276. https://doi.org/10.1038/s44220-024-00332-z
Joks, G., Su, S., & King, J. (2024). Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): Commentary, Joks et al. The British Journal of Psychiatry, 225(5), 515–516. https://doi.org/10.1192/bjp.2024.79
Kargbo, R. B. (2024). Harnessing Artificial Intelligence to Overcome Key Challenges in Psychedelic Research and Therapy. ACS Medicinal Chemistry Letters, 16(1), 3–7. https://doi.org/10.1021/acsmedchemlett.4c00548
Kozak, Z., & Aaronson, S. T. (2024). The Long Road Toward Equitable MDMA Treatment in the United States. The Journal of Clinical Psychiatry, 85(2). https://doi.org/10.4088/JCP.23com15224
Kozak, Z., & Miller, C. W. T. (2024). Beyond psychedelics: Set and setting in general psychiatric practice. International Review of Psychiatry, 1–8. https://doi.org/10.1080/09540261.2024.2419662
Lafrance, A., Spriggs, M. J., Gukasyan, N., & Peck, S. K. (2024). Beyond the numbers: Reimagining healing with psychedelics for eating disorders. Journal of Eating Disorders, 12(1), 148. https://doi.org/10.1186/s40337-024-01111-y
Lee, A., Rosenbaum, D., & Buchman, D. Z. (2024). Informed Consent to Psychedelic-Assisted Psychotherapy: Ethical Considerations. The Canadian Journal of Psychiatry, 69(5), 309–313. https://doi.org/10.1177/07067437231225937
Marks, M., Brendel, R. W., Shachar, C., & Cohen, I. G. (2024). Essentials of Informed Consent to Psychedelic Medicine. JAMA Psychiatry, 81(6), 611. https://doi.org/10.1001/jamapsychiatry.2024.0184
Mehtani, N. J., Anderson, B. T., & Mitchell, J. M. (2024). Psychedelics in Addiction Treatment-Navigating a Sociopolitical Rift. JAMA neurology, 10.1001/jamaneurol.2023.5173. Advance online publication. https://doi.org/10.1001/jamaneurol.2023.5173
Nigam, K., King, F., & Espi Forcen, F. (2024). Advancing ketamine in the treatment hierarchy for refractory depression. The British Journal of Psychiatry, 1–3. https://doi.org/10.1192/bjp.2024.217
O’Donnell, K. C., Grigsby, J., & Grob, C. S. (2024). Healing, Harms, and Humility: Expanding the Scope of Psychedelic-Assisted Psychotherapy Research. The American journal of psychiatry, 182(1), 13–16. https://doi.org/10.1176/appi.ajp.20230785
Oliveira-Maia, A. J., & Seybert, C. (2024). Dilemmas in psychedelic medicine: From ethics to regulation and equity. European Neuropsychopharmacology, 91, 67–68. https://doi.org/10.1016/j.euroneuro.2024.11.003
Pashdag, J. (2024). Non-hallucinogenic psychedelic psychotherapy: Decreasing risk and increasing access, or missing the point? Journal of Psychedelic Studies. https://doi.org/10.1556/2054.2024.00385
Reed, F., & Foldi, C. J. (2024). Do the therapeutic effects of psilocybin involve actions in the gut? Trends in Pharmacological Sciences, 45(2), 107–117. https://doi.org/10.1016/j.tips.2023.12.007
Sarris, J., Halman, A., Urokohara, A., Lehrner, M., & Perkins, D. (2024). Artificial intelligence and psychedelic medicine. Annals of the New York Academy of Sciences, nyas.15229. https://doi.org/10.1111/nyas.15229
Schenberg E. E. (2024). Psychedelic skepticism: back to the sixties? Therapeutic advances in psychopharmacology, 14, 20451253241243242. https://doi.org/10.1177/20451253241243242
Schenberg, E. E., Hauskeller, C., Schwarz, C. G., & King, F. (2024). Psychedelic therapies: Healing for the wrong reasons? Nature Mental Health, 2(11), 1265–1267. https://doi.org/10.1038/s44220-024-00344-9
Sebben, B., Stone, J., Sarris, J., Perkins, D., Mallie, K., Barnett, S., Ruffell, S. G. D., & Beesley, V. L. (2024). Psychedelic medicine and cultural responsiveness: A call for Aboriginal and Torres Strait Islander engagement in Australian clinical trials and practice. Australian and New Zealand Journal of Public Health, 48(6), 100200. https://doi.org/10.1016/j.anzjph.2024.100200
Sisti, D. (2024). Ethics in Psychedelic Science: Promises and Responsibilities. Journal of Clinical Psychopharmacology, 45(1), 1–3. https://doi.org/10.1097/JCP.0000000000001944
Simonsson, O., Goldberg, S. B., & Hendricks, P. S. (2024). Into the wild frontier: Mapping the terrain of adverse events in psychedelic-assisted therapies. Journal of psychopharmacology (Oxford, England), 2698811241292944. Advance online publication. https://doi.org/10.1177/02698811241292944
Smith, W. R., Sisti, D. A., & Appelbaum, P. S. (2024). The safety of supported psilocybin use in Oregon. Nature Medicine, 30(1), 17–18. https://doi.org/10.1038/s41591-023-02727-4
Stocker, K., & Liechti, M. E. (2024). Methylenedioxymethamphetamine is a connectogen with empathogenic, entactogenic, and still further connective properties: It is time to reconcile “the great entactogen—empathogen debate.” Journal of Psychopharmacology, 38(8), 685–689. https://doi.org/10.1177/02698811241265352
Sznitman, S. R., Broers, B., Auer, R., & Tal, K. (2024). Taking the potential harms of psychedelic-assisted therapy seriously: How do we prevent or mitigate the risks to vulnerable patients? International Journal of Drug Policy, 131, 104521. https://doi.org/10.1016/j.drugpo.2024.104521
Trout, K., & Daley, P. F. (2024). The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508. https://doi.org/10.1002/dta.3667
Wilkinson, S. T., Palamar, J. J., & Sanacora, G. (2024). The Rapidly Shifting Ketamine Landscape in the US. JAMA Psychiatry, 81(3), 221. https://doi.org/10.1001/jamapsychiatry.2023.4945
Miscellaneous
Breeksema, J. J., Niemeijer, A., Krediet, E., Karsten, T., Kamphuis, J., Vermetten, E., Van Den Brink, W., & Schoevers, R. (2024). Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: A qualitative study. Scientific Reports, 14(1), 2929. https://doi.org/10.1038/s41598-024-53188-9
“This paper explores patient experiences with psilocybin treatment through qualitative interviews, providing important insights into subjective experiences informing outcomes. This qualitative study is a valuable contribution to the psychedelic literature as it centers on patient narratives, offering a rich understanding of subjective experiences with psilocybin for treatment-resistant depression. Its strength lies in its focus on patient voices, which complements the growing body of quantitative research on psilocybin’s efficacy. This paper highlights individual variability in therapeutic outcomes and underscores the importance of integrating qualitative insights into clinical trial design and post-treatment integration practices. Given the small sample sizes of current clinical trials, I look forward to seeing more papers such as this one, with well-designed and intentional qualitative and mixed methods to bolster the evidence with more nuanced approaches to data collection, analysis, and application of findings.” – Meghan DellaCrosse
Calder, A. E., & Hasler, G. (2024). Validation of the Swiss Psychedelic Side Effects Inventory: Standardized assessment of adverse effects in studies of psychedelics and MDMA. Journal of Affective Disorders, 365, 258–264. https://doi.org/10.1016/j.jad.2024.08.091
“The lack of standardized measures to capture adverse side effects in psychedelic clinical trials is surprising. Publication of the Swiss Psychedelic Side Effects Inventory is an important development for the field, and should help better characterize the full spectrum of potential side effects with psychedelics as well improve comparability between studies.” – Jacob Aday
R., Rej, S., Gloeckler, S., Erritzoe, D., Carhart-Harris, R., & Greenway, K. T. (2024). Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy. Scientific Reports, 14(1), 16524. https://doi.org/10.1038/s41598-024-66817-0
“It’s exciting to see a publication following patient health outcomes after Health Canada’s decisions to provide access to psilocybin via two pathways: first, through individual-specific “Section 56” exemptions, and second, through the federal Special Access Program (“SAP”), allowing licensed physicians and NPs to prescribe the drug. We are seeing regulatory shifts and changes to legislature regarding access to psilocybin in many countries – this self-report, observational study by de la Salle et al. provides data (though limited in scope and with a very small number of participants) highlighting how individuals have been impacted by such changes in Canada. Adding to the body of real-world evidence, participants variously reported their psilocybin experience (accessed through SAP) as meaningful and insightful yet difficult – the authors conclude that such results align with results from clinical trials. Importantly, the authors note, “Use of the compassionate access pathways for PAP would greatly benefit from adopting the same high standards of psychological support and risk assessments currently employed in clinical trials, given adequate training and resources”. As the public shows increasing interest in removing barriers to accessing psilocybin therapy, studies such as this emphasize the need to simultaneously create frameworks for education and support that ensures safety standards and promotes harm-reduction.” – Juliet Meccia
Doss, M. K., Kloft, L., Mason, N. L., Mallaroni, P., Reckweg, J. T., Van Oorsouw, K., Tupper, N., Otgaar, H., & Ramaekers, J. G. (2024). Ayahuasca enhances the formation of hippocampal-dependent episodic memory without impacting false memory susceptibility in experienced ayahuasca users: An observational study. Journal of Psychopharmacology, 02698811241301216. https://doi.org/10.1177/02698811241301216
“Reading anecdotes from places like the r/ayahuasca subreddit, one cannot avoid noticing how often people report uncovering seemingly lost or never remembered memories of trauma or abuse. Some recent clinical research, too, has described clients worrying about the veracity of events they feel they have recalled under psychedelics for the first time. As a researcher in trauma and autobiographical memory, it’s difficult not to see the potential dangers here, keeping in mind the unethical recovered-memory therapies and Satanic ritual abuse panics of decades past. So, given that psychedelics appear to increase suggestibility and perceptions of salience and certainty, could they promote the formation of false memories? In this fascinating study by Manoj Doss and colleagues at least, pre-encoding administration of ayahuasca in fact appeared to enhance aspects of memory accuracy and did not increase susceptibility to false memories. Notably, the participants were Santo Daime members, very experienced ayahuasca users. Replication and extension of this research with more diverse samples is sorely needed. It will also be crucial to separate effects on the different memory phases, as here both encoding and retrieval took place under ayahuasca, and to test whether there is something specific about the effects of ayahuasca (e.g., due to the beta-carbolines present, as the authors suggest), as compared with other psychedelics.” – Samuli Kangaslampi
Eaton, E., Capone, C., Gully, B. J., Brown, Z. E., Monnig, M., Worden, M. S., Swift, R. M., & Haass-Koffler, C. L. (2024). Design and methodology of the first open-label trial of MDMA-assisted therapy for veterans with post-traumatic stress disorder and alcohol use disorder: Considerations for a randomized controlled trial. Contemporary Clinical Trials Communications, 41, 101333. https://doi.org/10.1016/j.conctc.2024.101333
“This protocol is notable for being the first VA-funded trial (in addition to NIAAA funds) of MDMA-AT, building on evidence from the BIMA study. Substance use disorder is highly co-occurring with PTSD in veterans – the rule not the exception at 63% – and treating each individually has limitations; therefore, interventions to address both are urgently needed for this comorbid population which experiences more severe symptomatology. A significant contribution of this study design will be the neuroimaging and biomarker data, which are included to evaluate connectivity changes and neuroinflammation, pre- and -post treatment. The therapeutic component, meanwhile, aims to disrupt patterns of alcohol use that are associated with self-medication in PTSD.
The authors review their study start-up activities to date as well as study structure (only 2 medication sessions + prep/integration), hypotheses, analysis plan, and outcomes, i.e. the FDA-approved clinical outcome assessments (COAs) for alcohol reduction (TLFB) as primary, and PTSD symptom reduction (CAPS-5) as secondary. Interestingly, they discuss the challenges they grappled with in this study design, particularly around the health monitoring needs in this potentially higher cardiac-risk population, and measures to mitigate and assess for tolerability.” – Hailey Gilmore
Izmi, N., Carhart-Harris, R. L., & Kettner, H. (2024). Psychological effects of psychedelics in adolescents. Frontiers in Child and Adolescent Psychiatry, 3, 1364617. https://doi.org/10.3389/frcha.2024.1364617
“Similarly to the other adolescent psychedelic study (Simonsson et al., 2024), I was thrilled to see more work being done in this area. I think that both the adolescent papers that came out in 2024 had their strengths and weaknesses. The strength of this paper was the direct comparison of adolescents and young adults (ages 16-24) to adults (over age 25). While the study was an observational self-report, the direct comparison of these two groups yields important information about psychiatric symptoms and psychedelic use. The findings are intriguing as well because they find improvements in well-being and mental health, but at the same time acute subjective effects are conveyed as more negative in adolescents. Further, higher prevalence of hallucinogen persisting perceptual disorder (HPPD)-related symptoms was found in adolescent populations. This begs the question…is earlier use of psychedelics a potential risk factor for developing HPPD? I can’t wait to see more research to that end.” – Alaina Jaster
Kuiper, H., Alley, C., Harris, Z., Kuiper Rauch, C., Robbins, M., Rodriguez, P., Tomczak, P., Urrutia, J., & Magar, V. (2024). Psychedelic public health: State of the field and implications for equity. Social Science & Medicine, 357, 117134. https://doi.org/10.1016/j.socscimed.2024.117134
“Founders of the Center for Psychedelic Public Health, cover one of the most exciting potentialities in the psychedelic space, elevating the power of inter-field knowledge-sharing. This review characterizes current Schools and Programs of Public Health (SPPH) involvement in Psychedelic Research Centers (PRC). Given the nascent stage, it was unsurprising they found that the involvement of SPPH in PRC was limited, and faculty of PRC were not often from PH backgrounds. What’s more, while reciprocity and equity are core public health principles, and given the predominance of Indigenous knowledge in psychedelic practice, Indigeneity was not prominently or commonly addressed, and PRCs included limited Indigenous leadership.
There is significant overlap of public health expertise with emergent needs of the psychedelic space, notably: social determinants of health; health promotion strategy; addressing mental health crises and intersecting vulnerabilities; harm reduction principles; engagement with public policy; understanding of community as a key driver and dynamic; proven methodology for implementing and scaling interventions; an embrace of holistic health and the nested ecologies of individual /community/societal health; focus on health equity; and systems mapping and impact evaluation. With this initial work, one hopes that much future research is inspired to leverage this synergy and avoid missed opportunities, thereby giving researchers, practitioners and policymakers the best shot at balancing the risk/benefit profile of psychedelics as they proliferate to the broader population.
That is, pending the future of public health – which already navigates the challenges of the Controlled Substances Act and other federal regulations, but more importantly – which largely occurs via dedicated federal funding and offices within Health & Human Services.” – Hailey Gilmore
Maples-Keller, J. L., Dunlop, B. W., & Rothbaum, B. O. (2024). The METEMP protocol: Massed exposure therapy enhanced with MDMA for PTSD. Contemporary Clinical Trials Communications, 43, 101400. https://doi.org/10.1016/j.conctc.2024.101400
“This open label pilot of 100 mg MDMA in combination with massed exposure therapy (PE) for PTSD, leverages a VA Gold standard treatment, which has both translational support and potential for dissemination. PE uses fear extinction as a mechanism, aided in this protocol by the pharmacologic action of the MDMA. The massed approach has prior evidence in the ongoing Wounded Warriors-funded project at Emory, which consists of PE daily for two weeks instead of the usual once per week for several months. This leads to comparable effect and durability of the traditional approach, and a robust 96% completion rate compared to 30-50% dropout in the regular schedule.
The study builds on the team’s prior healthy human RCT studying fear extinction learning in which the MDMA group were more likely to retain fear extinction than placebo. Additionally, prior PE trials have shown high responders demonstrated significant extinction retention learning, compared to low responders whose fear returned. Finally, the authors postulate the 2-week treatment period as being optimal for neural plasticity, citing the Nardou et al. paper indicating that the social reward learning critical period remained open in mice that long following MDMA administration.
The pilot study is considered a “treatment development” protocol since best practices for incorporating the strong subjective effects of MDMA with imaginal exposure procedures need to be studied for feasibility and potentially refined. Novel elements include a handout provided on use of touch and available options, and skin conductance electrodes track physiological response during imaginal exposure, which occurs twice – 90 minutes and 240 minutes – into the MDMA experience, between which participants are encouraged in MAPS-lingo to “go inside”.
The strong dissemination potential lies in VA centers’ mandate to provide either PE or CPT for PTSD, with large numbers of providers trained in each, and the single dose (compared to the 3 in the Lykos protocols) could easily be incorporated into many different ongoing program models. The team seeks to further streamline implementation burdens by having 2 therapists present only for the first 3 of the 10 total sessions, as opposed to 2 therapists for all.” – Hailey Gilmore
Mathai, D. S., Hull, T. D., Vando, L., & Malgaroli, M. (2024). At-home, telehealth-supported ketamine treatment for depression: Findings from longitudinal, machine learning and symptom network analysis of real-world data. Journal of Affective Disorders, 361, 198–208. https://doi.org/10.1016/j.jad.2024.05.131
“This study on telehealth-supported ketamine treatment represents a significant contribution to the field, primarily due to its unprecedented scale (n=11,441) and use of machine learning and network analysis to study treatment outcomes and predictors. The identification of depressed mood and anhedonia as symptoms that sustain depression despite ketamine treatment points to important targets for augmentation strategies. The promising findings and low adverse events of using a digital intervention address a critical access barrier in psychedelic medicine and offer a blueprint to scale ketamine-assisted treatments in a cost-effective manner.” – Matteo Malgaroli
Morland, L. A., Perivoliotis, D., Wachsman, T. R., Alam, A., Knopp, K., Khalifian, C., Ramanathan, D., Chargin, B. E., Bismark, A. W., Glynn, S., Stauffer, C., & Wagner, A. C. (2024). MDMA-assisted brief cognitive behavioral conjoint therapy for PTSD: Study protocol for a pilot study. Contemporary Clinical Trials Communications, 40, 101314. https://doi.org/10.1016/j.conctc.2024.101314
“PTSD impacts both individual and relational functioning, particularly among veteran couples who face unique challenges, and a cyclic relationship exists between PTSD symptoms, overall veteran health, and health of relationships. The VA is the largest provider of PTSD treatment in the world. This intervention acts on the unit of the dyad, using brief Cognitive Behavioral Conjoint Therapy (bCBCT) – a VA accepted couples-level PTSD intervention – as the integration model for 2 MDMA sessions. It is brief – and therefore perhaps more scalable – because it is reduced from the usual 15 sessions to 8, which are delivered in a massed approach. Integration also includes two couple-level emotion- focused sessions using a technique of “empathic joining” to support couples in developing a deeper understanding of and connection with one another following MDMA sessions.
The team is building on the work of Monson et al. who gave couples a condensed 15 session CBCT and 2 MDMA session intervention, which saw large improvements in PTSD in the PTSD+ partner and medium to large improvements in partner mental health and relationship functioning. However, due to VA regulations prohibiting MDMA administration to non-veteran partners, only the veteran receives MDMA in this study. Eight couples are participating in this single site open label study, which in addition to looking at CAPS-5 (primary) is measuring outcomes on the Couples Satisfaction Index (CSI-32, secondary). The study further pulls implementation levers by utilizing 2 therapists for dosing, but only 1 therapist to deliver the bCBCT. Dose escalation occurs as in the MAPS/Lykos studies, though at slightly lower levels due to active engagement during medicine sessions, since the partner is present for part of them. Another strength of the study is evaluating outcomes out to 6 months post-treatment.
A notable element of the analytic plan is to include a moderation analysis of LEC-5 and ACE on CAPS scores. The team plans to proceed to a larger RCT if there is a signal.” – Hailey Gilmore
Myran, D. T., Pugliese, M., Xiao, J., Kaster, T. S., Husain, M. I., Anderson, K. K., Fabiano, N., Wong, S., Fiedorowicz, J. G., Webber, C., Tanuseputro, P., & Solmi, M. (2024). Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2024.3532
“Myran et al. (2024) analysed a dataset of over nine million visits to Canadian emergency departments (2008-2021) and picked out 5,217 cases involving hallucinogen use. They then tracked how many of these patients developed a schizophrenia spectrum disorder (SSD – a seldom-used umbrella term for schizophrenia, a psychotic disorder, and schizotypal personality disorder, which is a less severe condition characterised by unusual thinking, eccentric behaviours, and social isolation) over the next three years. The results indicated that hallucinogen users had three-to-four times greater odds of receiving this diagnosis than the general population – even after adjusting for pre-existing substance use and mental health problems.
It is important that we take these findings with a pinch of salt. The definition of ‘hallucinogens’ was very broad, with known neurotoxic substances (e.g. PCP and amphetamines) included alongside LSD, MDMA and psilocybin. It is telling that for the subgroup of patients coded as ‘LSD poisoning’ there was no significant increase in rates of SSD. It is also difficult to conclude that the patients who did receive the diagnosis were not taking adulterated or mis-labelled LSD.
It is also possible that a “third variable” might have influenced results. We wondered whether there could be causative factors that increase hallucinogen use and risk of SSD. For example, we know that adverse childhood experiences are associated with drug abuse and psychosis later in life. The authors acknowledge this in the paper and speculate that the earliest phases (“prodrome”) of psychosis may be associated with an increased interest in mind-altering substances.
We believe that this paper is helpful for our work in the emergency department. It has encouraged us to be inquisitive about patients who come in after taking hallucinogens. What is motivating them? Do they feel they are self-medicating a different problem? Are they having any unusual experiences when they are not tripping? Most users of these drugs are psychologically well, but if there is a vulnerable minority – as is suggested by this study – then it is probably good to identify them sooner rather than later. They may benefit from a supportive conversation and sign-posting to mental health services.” – Gregory Yates & Harriet Phelan
“The risk of developing psychosis is one of the most concerning side effects associated with psychedelic use. Myran et al., evaluated whether individuals who visited the emergency department for hallucinogen-related issues subsequently developed schizophrenia spectrum disorder. Their analysis revealed a 21-fold increased risk compared to the general population. This heightened vulnerability persisted even after controlling for other substance use and mental health conditions. These alarming findings underscore the need for proactive follow-up and preventive strategies for this high-risk group.” – Lucie Berkovitch
Palitsky, R., Kaplan, D. M., Perna, J., Bosshardt, Z., Maples-Keller, J. L., Levin-Aspenson, H. F., Zarrabi, A. J., Peacock, C., Mletzko, T., Rothbaum, B. O., Raison, C. L., Grant, G. H., & Dunlop, B. W. (2024). A framework for assessment of adverse events occurring in psychedelic-assisted therapies. Journal of psychopharmacology (Oxford, England), 38(8), 690–700. https://doi.org/10.1177/02698811241265756
“The systematic assessment of adverse events (AEs) in P-AT remains an important challenge for researchers and clinicians. With psychedelics not yet licensed, regulators rightly demand robust information about adverse events as well as treatment efficacy. Yet there is considerable room for improvement on AE reporting in psychedelic trials: a systematic review and meta-analysis last year found that nearly half of psychedelic trials reported no AE data whatsoever, and only 23.5% of post-2005 trials reported systematic approaches for ascertaining AEs (Hinkle et al., 2024).
The typical definition of AE deployed in standard pharmaceutical trials is “any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.” While this definition is appropriate for conventional pharmacotherapy, it may not adequately capture the full spectrum of challenging outcomes that may follow P-AT. Scholars are increasingly recognising this gap and developing specialised tools to address it, with Palitsky and colleagues’ Psychedelic Assisted Therapy Adverse Events assessment protocol (PATAE) joining the Swiss Psychedelic Side Effect Inventory (SPSI, Calder & Hasler, 2024) among last year’s important contributions to this evolving conversation.
At the heart of PATAE is the recognition that P-AT’s distinctive characteristics —combining pharmacological effects, psychotherapeutic processes, and spiritual-existential dimensions— require tailored approaches to AE detection. The framework developed by Palitsky et al. acknowledges that not all adversities arising from P-AT are best understood as “medical” in nature. They propose 54 AEs to track across seven categories specifically relevant to P-AT—sociocultural, psychospiritual, interpersonal, behavioural, psychotherapy-related, affective/cognitive/metacognitive, and perceptual—outcomes that are broadly invisible to standard AE frameworks.
The paper from Palitsky et al. implicitly raises an important issue about the entire enterprise of AE assessment: the question of what constitutes an adverse event is not merely technical but normative. Much as we may strive to be objective in scientific research, our measurement systems inevitably encode judgments about which outcomes matter and which don’t. When we privilege certain types of outcomes (like “adverse drug reactions”) over others (like shifts in worldview, difficulties in integration, or newly-challenging relationship dynamics), we risk imposing a narrow conception of what constitutes therapeutic success that may not align with patients’ own priorities and concerns. Palitsky’s framework invites us to reconsider what forms of adversity merit attention in P-AT. This is not merely a methodological choice, but a value-laden one with real implications for patients and for the development of the field itself.
The ethical implications of this measurement gap extend beyond research methodology into the realm of informed consent and patient autonomy. From an ethical perspective, what matters for informed consent is not whether an outcome meets regulatory criteria for an AE, but whether knowledge of its possibility would materially affect a prospective patient’s decision-making. By prioritising patient narratives and subjective appraisals over clinician determinations of therapeutic value, PATAE represents an important step toward fulfilling our ethical duty to properly inform patients about outcomes that may be highly salient to them, regardless of whether those outcomes fit neatly into conventional AE categories.
While offering an ambitious and much-needed expansion of what counts as “adverse,” the framework’s comprehensiveness raises important practical questions about implementation. The tension between thorough detection and feasible assessment represents one more dilemma for the field. As Cheung et al. note in their commentary on this paper, any assessment framework must balance the twin imperatives of comprehensiveness and practicality. A protocol too burdensome may lead to poor compliance and incomplete data collection; one too sparse may miss crucial outcomes.
The challenge ahead lies in operationalising these expanded AE criteria in a way that enhances both research integrity and patient care, without compromising feasibility or clinical applicability. At stake is not just regulatory compliance, but our capacity to understand the true risk:benefit profile of P-AT, and to communicate that understanding accurately to those who might wish to experience it.” – Eddie Jacobs
Simon, M. W., Olsen, H. A., Hoyte, C. O., Black, J. C., Reynolds, K. M., Dart, R. C., & Monte, A. A. (2024). Clinical Effects of Psychedelic Substances Reported to United States Poison Centers: 2012 to 2022. Annals of Emergency Medicine, 84(6), 605–618. https://doi.org/10.1016/j.annemergmed.2024.06.025
“Simon et al. (2024) reviewed 54,605 medical cases (2012-2022) in which ‘psychedelic exposures’ had required consultation with a poison centre in the US. The majority of patients in this study (87%) were taken to the emergency department and over half were reported to have ‘symptoms that required treatment, severe residual or prolonged symptoms, or death.’ From these findings the authors concluded that ‘[i]ncreases in psychedelic use may lead to increased frequency of adverse events and health care utilization.’
The trouble with this conclusion is that many of the drugs taken in this study were not what we would consider in emergency medicine to be ‘psychedelics,’ by convention or pharmacology. Ketamine (6.3%) and PCP (11%) were included, as were methamphetamine and its derivatives under the header ‘hallucinogenic amphetamines’ (40.6%). As might be expected, the worst outcomes were seen with these drugs, and not the minority of the sample using LSD (17.7%) or mushrooms (13.8%).
Fortunately, because the authors shared drug-specific data, we can make our own conclusions about the ‘adverse events’ in the study. And it seems there were indeed problems with psychedelics. Looking at LSD, for example, roughly half the sample required sedation and a concerning number (5.7%) required ‘intubation / ventilation’ — which is our shorthand for a patient who needs to be put into a “medical coma” and transferred to the intensive care unit with a breathing tube in. But this was unsurprising. The patients in this study were a sick minority. They required treatment in hospital and referral to a poison centre, which is inherently an ‘adverse event’ for psychedelic users. Individuals who were able to cope with a bad trip at home, or who were easily managed in the emergency department, would not have made it into this dataset.
Our impression overall was this: the data clearly show that psychedelics are not without risk — almost nothing is! – but it is reassuring that even in the most severe subset of patients, true emergencies are rare. We do not anticipate that increased use of psychedelics will change the situation for us in hospital. Cocaine, amphetamines, and alcohol will still be the biggest troublemakers.” – Gregory Yates & Harriet Phelan
Simonsson, O., Mosing, M. A., Osika, W., Ullén, F., Larsson, H., Lu, Y., & Wesseldijk, L. W. (2024). Adolescent Psychedelic Use and Psychotic or Manic Symptoms. JAMA Psychiatry, 81(6), 579. https://doi.org/10.1001/jamapsychiatry.2024.0047
“This was one of my favorite papers from 2024 because it’s one of the first to examine adolescent use of psychedelics. This cross-sectional study utilized a large sample of adolescent twins assessed at multiple ages over adolescence and young adulthood to determine association between past psychedelic use and psychotic or manic symptoms at age 15. The findings suggest that naturalistic use of psychedelics may be associated with lower rates of psychotic symptoms among adolescents, but the use of psychedelics and manic symptoms may have an interaction related to genetic vulnerability to disorders like schizophrenia and some types of bipolar. Given adolescence is such an important time for brain development and the development of neuropsychiatric symptoms, these studies are very necessary. I was excited to see more interest in this topic in 2024 and hope it continues this year.” – Alaina Jaster
Weiss, B., Roseman, L., Giribaldi, B., Nutt, D.J., Carhart-Harris, R.L., Erritzoe, D. (2024). Unique Psychological Mechanisms Underlying Psilocybin Therapy Versus Escitalopram Treatment in the Treatment of Major Depressive Disorder. Int J Ment Health Addiction, 22, 806–841. https://doi.org/10.1007/s11469-024-01253-9
“This article not only presents important empirical findings of differential psychological mechanisms of therapeutic action that distinguish psychedelic therapy and treatment with SSRIs but also elaborates rich and nuanced comparative theoretical models for interpreting these findings that vitally contribute to an understanding of psychedelic therapy as essentially a form of psychotherapy.” – CJ Healy
Yaden, M. E., Ching, T. H. W., Goldway, N., Roberts, D. E., Hokanson, J., Gukasyan, N., Pittenger, C., Kelmendi, B., Ross, S., Glick, G., & O’Donnell, K. C. (2024). Psychedelic medicine in psychiatry residency training: A survey of psychiatric residency program directors. International Review of Psychiatry, 1–6. https://doi.org/10.1080/09540261.2024.2397039
“It’s one thing to be excited about the potential benefits of psychedelic therapies but another thing entirely to understand the state of the research and how psychedelics might be safely used as clinical tools. This work by Dr. Mary Yaden and colleagues illuminates significant gaps in current education and training for US Psychiatry programs, which are likely to exist for other training programs also. Importantly, this group of educators is also working toward addressing this need through the development of a first-of-its-kind standardized curriculum for psychedelic education.” – David Mathai
Yoo, M., & Sakopoulos, S. (2024). The Birth of the Psychedelic Industry: Capitalising on the Psychedelic Renaissance. Future Humanities, 3(1), e70004. https://doi.org/10.1002/fhu2.70004
“An important publication that should be essential reading for everyone operating in this sector – from research to industry. As psychedelics are pushed through the R&D pipeline towards commercialization, it is critical to pause, reflect, and consider the ramifications of who will control the playing field, and who will be left on the sidelines. While the “psychedelic renaissance” is often framed as a breakthrough in mental health treatment, Yoo & Sakopoulos highlight the underlying financial and corporate interests that shape how these substances are studied, marketed, and accessed. Stepping outside our idealistic bubbles, we can ask ourselves: what are we working towards? Are we operating ethically? Who are we helping? Who are we leaving out? What interests are at play?” – Juliet Meccia
The above publications received comments from the researchers we surveyed. Here are further 2024 publications that Michael included in his list.
***
Aday, J. S., Bloesch, E. K., Davis, A. K., Domoff, S. E., Scherr, K., Woolley, J. D., & Davoli, C. C. (2024). Increases in Aesthetic Experience Following Ayahuasca Use: A Prospective, Naturalistic Study. Journal of Humanistic Psychology, 00221678241230609. https://doi.org/10.1177/00221678241230609
Aday, J. S., Boehnke, K. F., Herberholz, M., & Kruger, D. J. (2024). Attitudes of psychedelic users regarding cost of treatment and non-hallucinogenic alternatives. Journal of Psychedelic Studies. https://doi.org/10.1556/2054.2024.00354
Aicher, H., & Gasser, P. (2024). Treatment Recommendations for Psychedelic-assisted Therapy. Swiss Archives of Neurology, Psychiatry and Psychotherapy. https://doi.org/10.4414/sanp.2024.1488043038
Angyus, M., Osborn, S., Haijen, E., Erritzoe, D., Peill, J., Lyons, T., Kettner, H., & Carhart-Harris, R. (2024). Validation of the imperial psychedelic predictor scale. Psychological Medicine, 54(12), 3539–3547. https://doi.org/10.1017/S0033291724002204
Back, A., Myers, S., Guy, J., Perez, J., Lazar Thorn, L., & McGregor, B. (2024). Evolving Guidelines for the Use of Touch During a Clinical Trial of Group Psilocybin-Assisted Therapy. Psychedelic Medicine, 2(4), 187–191. https://doi.org/10.1089/psymed.2023.0069
Barba, T., Kettner, H., Radu, C., Peill, J. M., Roseman, L., Nutt, D. J., Erritzoe, D., Carhart-Harris, R., & Giribaldi, B. (2024). Psychedelics and sexual functioning: A mixed-methods study. Scientific Reports, 14(1), 2181. https://doi.org/10.1038/s41598-023-49817-4
Barbut Siva, J., Barba, T., Kettner, H., Kuc, J., Nutt, D. J., Carhart-Harris, R., & Erritzoe, D. (2024). Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study. Journal of psychopharmacology (Oxford, England), 38(2), 145–155. https://doi.org/10.1177/02698811231224217
Bayes, A., Cao, T. V., Barreiros, A. R., Massaneda-Tuneu, C., Dong, V., Thornton, N., Glozier, N., Beesley, L., Moreno, D., Gálvez-Ortiz, V., Short, B., Martin, D., & Loo, C. (2024). Safety outcomes of ketamine for treatment-resistant depression in clinical settings and development of the ketamine side effect tool-revised (KSET-R). Psychiatry Research, 344, 116334. https://doi.org/10.1016/j.psychres.2024.116334
Bhagavan, C., Kanaan, R., Carter, O., Nielsen, G., Berlowitz, D., Issak, S., Braat, S., Zaloumis, S., Attard, Z., Oliver, G., Mayne, D., McKernon, D., Roebuck, G., Rucker, J., Butler, M., & Bryson, A. (2024). Psilocybin and Motor Function: A Triple‐Blind, Dose‐Finding Study in Healthy Participants. Psychiatric Research and Clinical Practice, 6(4), 164–174. https://doi.org/10.1176/appi.prcp.20240047
Bradley, M., Grossman, D., Simonsson, O., Copes, H., & Hendricks, P. S. (2024). Rural‐urban divide in risk perception of LSD: Implications for psychedelic‐assisted therapy. The Journal of Rural Health, 41(1), e12906. https://doi.org/10.1111/jrh.12906
Bradshaw, A. J., Ramírez-Cruz, V., Awan, A. R., Furci, G., Guzmán-Dávalos, L., & Dentinger, B. T. M. (2024). Phylogenomics of the psychoactive mushroom genus Psilocybe and evolution of the psilocybin biosynthetic gene cluster. Proceedings of the National Academy of Sciences, 121(3), e2311245121. https://doi.org/10.1073/pnas.2311245121
Buchman, D., & Rosenbaum, D. (2024). Psychedelics in PERIL: The Commercial Determinants of Health, Financial Entanglements and Population Health Ethics. Public Health Ethics, 17(1–2), 24–39. https://doi.org/10.1093/phe/phae002
Calder, A. E., Qualls, C., Hasler, G., Elmiger, D., & Strassman, R. (2024). The Hallucinogen Rating Scale: Updated factor structure in a large, multi-study sample. Biological Psychiatry Global Open Science, 100436. https://doi.org/10.1016/j.bpsgos.2024.100436
Calder, A. E., Rausch, B., Liechti, M. E., Holze, F., & Hasler, G. (2024). Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response. Journal of Psychopharmacology, 38(10), 873–886. https://doi.org/10.1177/02698811241278873
Cherian, K. N., Keynan, J. N., Anker, L., Faerman, A., Brown, R. E., Shamma, A., Keynan, O., Coetzee, J. P., Batail, J.-M., Phillips, A., Bassano, N. J., Sahlem, G. L., Inzunza, J., Millar, T., Dickinson, J., Rolle, C. E., Keller, J., Adamson, M., Kratter, I. H., & Williams, N. R. (2024). Magnesium–ibogaine therapy in veterans with traumatic brain injuries. Nature Medicine, 30(2), 373–381. https://doi.org/10.1038/s41591-023-02705-w
Clemens, K., Zhdanava, M., Teeple, A., Voegel, A., Joshi, K., Shah, A., Chen, C., & Pilon, D. (2024). Impact of social determinants of health on esketamine nasal spray initiation among patients with treatment-resistant depression in the United States. Journal of Managed Care & Specialty Pharmacy, 31(1), 101–111. https://doi.org/10.18553/jmcp.2025.24240
Copa, D., Erritzoe, D., Giribaldi, B., Nutt, D., Carhart-Harris, R., & Tagliazucchi, E. (2024). Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity. Journal of Affective Disorders, 353, 60–69. https://doi.org/10.1016/j.jad.2024.02.089
d’Andrea, G., Pettorruso, M., Di Lorenzo, G., Rhee, T. G., Chiappini, S., Carullo, R., Barlati, S., Zanardi, R., Rosso, G., Di Nicola, M., Andriola, I., Marcatili, M., Clerici, M., Dell’Osso, B. M., Sensi, S. L., Mansur, R. B., Rosenblat, J. D., Martinotti, G., & McIntyre, R. S. (2024). The rapid antidepressant effectiveness of repeated dose of intravenous ketamine and intranasal esketamine: A post-hoc analysis of pooled real-world data. Journal of Affective Disorders, 348, 314–322. https://doi.org/10.1016/j.jad.2023.12.038
Daldegan-Bueno, D., Donegan, C. J., Forsyth, A., Sumner, R. L., Murphy, R. J., Menkes, D. B., Evans, W., Hoeh, N., Sundram, F., Reynolds, L. M., Ponton, R., Cavadino, A., Smith, T., Roop, P., Allen, N., Abeysinghe, B., Svirskis, D., Bansal, M., & Muthukumaraswamy, S. (2024). LSDDEP2: Study protocol for a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients with major depressive disorder. Trials, 25(1), 560. https://doi.org/10.1186/s13063-024-08384-3
Darke, S., Duflou, J., Peacock, A., Farrell, M., Hall, W., & Lappin, J. (2024). A retrospective study of the characteristics and toxicology of cases of lysergic acid diethylamide (LSD)‐ and psilocybin‐related death in Australia. Addiction, 119(9), 1564–1571. https://doi.org/10.1111/add.16518
De Wit, H., Hahn, E., Smadi, S., Li, T., & Molla, H. (2024). MDMA as well as amphetamine and alcohol increase feelings of social closeness in healthy adults. Scientific Reports, 14(1), 31312. https://doi.org/10.1038/s41598-024-82632-z
Dutcher, E. G., & Krystal, A. D. (2024). Treatment Expectancies and Psilocybin vs Escitalopram for Depression. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2024.4387
Earleywine, M., & Gomez, S. G. (2024). Is Personal Experience Essential for Effective Psychedelic Therapists?: The Challenges of Small, Accumulating Therapist Effects. Psychedelic Medicine, 2(3), 138–145. https://doi.org/10.1089/psymed.2023.0054
Farah, R., Kerns, A. F., Murray, A. C., & Holstege, C. P. (2024). Psilocybin Exposures Reported to U.S. Poison Centers: National Trends Over a Decade. Journal of Adolescent Health, 74(5), 1053–1056. https://doi.org/10.1016/j.jadohealth.2024.01.027
Gloeckler, S. G., Lehmann, A., De La Salle, S., Greenway, K. T., & Lucas, P. (2024). Preferences and Attitudes Toward Music in Nonclinical Uses of Psychedelics. Psychedelic Medicine, 2(4), 201–209. https://doi.org/10.1089/psymed.2024.0003
Gloeckler, S. G., Lévesque, J. T., Lehmann, A., Farzin, H., & Greenway, K. T. (2024). Music and non-music approaches in psilocybin-assisted psychotherapy: The sound of silence. Journal of Psychedelic Studies. https://doi.org/10.1556/2054.2024.00421
Glynos, N. G., Baker, A., Aday, J. S., Pouyan, N., Barron, J., Herberholz, M., Kruger, D., & Boehnke, K. F. (2024). Going Underground: Demographics, Services, and Best Practices Endorsed by Practitioners Providing Support for Naturalistic Psychedelic Use. Journal of Psychoactive Drugs, 1–11. https://doi.org/10.1080/02791072.2024.2405685
Graziosi, M., Rohde, J. S., Lake, S., Lucas, P., Kaufman, S. B., & Yaden, D. B. (2024). Developing a short form of the Awe Experience Scale (AWE-SF) in psychedelic samples. PLOS ONE, 19(12), e0314469. https://doi.org/10.1371/journal.pone.0314469
Henningfield, J. E., Belouin, S. J., Yaden, D. B., Urrutia, J., Anderson, B. T., Berger, A., Grob, C. S., Labate, B. C., Maier, L. J., Maternowska, M. C., Weichold, F., & Magar, V. (2024). In Memoriam: Roland R. Griffiths (July 19, 1946–October 16, 2023). Journal of Psychoactive Drugs, 56(3), 299–300. https://doi.org/10.1080/02791072.2024.2343812
Høgsted, E. S., Beliveau, V., Ozenne, B., Madsen, M. K., Svarer, C., Dam, V. H., Johansen, A., Fisher, P., Knudsen, G. M., Frokjaer, V. G., & Sankar, A. (2024). Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression. The British Journal of Psychiatry, 1–7. https://doi.org/10.1192/bjp.2024.143
Honk, L., Stenfors, C. U. D., Goldberg, S. B., Hendricks, P. S., Osika, W., Dourron, H. M., Lebedev, A., Petrovic, P., & Simonsson, O. (2024). Longitudinal associations between psychedelic use and psychotic symptoms in the United States and the United Kingdom. Journal of Affective Disorders, 351, 194–201. https://doi.org/10.1016/j.jad.2024.01.197
Hurst, K. T., Vogeley, A., Greenstein, D. K., Durland, L., Makel, S., Wang, P. R., Yavi, M., Zarate, C. A., & Ballard, E. D. (2024). Long-term follow-up of participants in ketamine clinical trials for mood disorders. Journal of Affective Disorders, 357, 134–137. https://doi.org/10.1016/j.jad.2024.04.062
Jackson, E. S., Goldway, N., Gerlach-Houck, H., & Gold, N. D. (2024). Stutterers’ experiences on classic psychedelics: A preliminary self-report study. Journal of Fluency Disorders, 81, 106062. https://doi.org/10.1016/j.jfludis.2024.106062
Jones, G., Lowe, M. X., Nayak, S., Sepeda, N., Kettner, H., Carhart-Harris, R., Jackson, H., & Garcia-Romeu, A. (2024). Examining differences in the effects and contexts of naturalistic psilocybin use for White participants vs. Participants of Color: A longitudinal online survey study. Journal of Affective Disorders, 370, 54–61. https://doi.org/10.1016/j.jad.2024.10.058
Jylkkä, J. (2024). Comforting delusions? How to evaluate the plausibility of mystical-type insights in psychedelic experiences. Philosophical Psychology, 1–31. https://doi.org/10.1080/09515089.2024.2391433
Jylkkä, J., Krabbe, A., & Jern, P. (2024). Endorsement of metaphysical idealism mediates a link between past use of psychedelics and wellbeing. Scientific Reports, 14(1), 13276. https://doi.org/10.1038/s41598-024-63687-4
Kargbo R. B. (2024). Advances in Psychedelic Therapeutics: Novel Prodrugs and Derivatives for Enhanced Mental Health Treatment. ACS medicinal chemistry letters, 15(12), 2071–2073. https://doi.org/10.1021/acsmedchemlett.4c00519
Kargbo R. B. (2024). Expanding the Therapeutic Horizons of Psilocybin in Mental Health. ACS medicinal chemistry letters, 15(11), 1821–1823. https://doi.org/10.1021/acsmedchemlett.4c00488
Kargbo R. B. (2024). Innovative Psychedelic Therapies: Harnessing 5-MeO-DMT and DMT for Mental Health Treatment. ACS medicinal chemistry letters, 15(11), 1812–1814. https://doi.org/10.1021/acsmedchemlett.4c00490
Kargbo R. B. (2024). Advancements in Psychoactive Alkaloid Delivery, Neuroenhancement, and Psychedelic Therapies: Exploring the Frontiers of Modern Pharmacology. ACS medicinal chemistry letters, 15(6), 755–757. https://doi.org/10.1021/acsmedchemlett.4c00181
Kargbo R. B. (2024). Current Trends in Psychedelic Science: Integrating Modified Lysergic Acid Derivatives and Psilocybin in Modern Medicine. ACS medicinal chemistry letters, 15(9), 1443–1445. https://doi.org/10.1021/acsmedchemlett.4c00414
Kettner, H., Roseman, L., Gazzaley, A., Carhart-Harris, R. L., & Pasquini, L. (2024). Effects of Psychedelics in Older Adults: A Prospective Cohort Study. The American Journal of Geriatric Psychiatry, 32(9), 1047–1059. https://doi.org/10.1016/j.jagp.2024.05.007
Kim, Y., Bigley, R., DeVinney, A., & Nestadt, P. S. (2024). The many faces of psilocybin-related psychosis: A case series. Psychiatry Research Case Reports, 4(1), 100243. https://doi.org/10.1016/j.psycr.2024.100243
Kirlić, N., Lennard-Jones, M., Atli, M., Malievskaia, E., Modlin, N. L., Peck, S. K., Gaillard, A., Goodwin, G. M., & Koelpin, D. (2024). Compass Psychological Support Model for COMP360 Psilocybin Treatment of Serious Mental Health Conditions. American Journal of Psychiatry, 182(1), 126–132. https://doi.org/10.1176/appi.ajp.20230884
Korman, B. A. (2024). Does LSD confer lasting psychological resilience? An investigation of naturalistic users experiencing job loss. PLOS ONE, 19(6), e0304991. https://doi.org/10.1371/journal.pone.0304991
Korthuis, P. T., Hoffman, K., Wilson-Poe, A. R., Luoma, J. B., Bazinet, A., Pertl, K., Morgan, D. L., Cook, R. R., Bielavitz, S., Myers, R., Wolf, R. C., McCarty, D., & Stauffer, C. S. (2024). Developing the Open Psychedelic Evaluation Nexus consensus measures for assessment of supervised psilocybin services: An e-Delphi study. Journal of Psychopharmacology, 38(8), 761–768. https://doi.org/10.1177/02698811241257839
Kruger, D. J., Aday, J. S., Fields, C. W., Kolbman, N., Glynos, N., Barron, J., Herberholz, M., & Boehnke, K. F. (2024). Psychedelic Therapist Sexual Misconduct and Other Adverse Experiences Among a Sample of Naturalistic Psychedelic Users. Psychedelic Medicine, psymed.2024.0011. https://doi.org/10.1089/psymed.2024.0011
Langlitz, N., & Gearin, A. K. (2024). Psychedelic Therapy as Form of Life. Neuroethics, 17(1), 14. https://doi.org/10.1007/s12152-024-09550-9
Leistenschneider, G., Majić, T., Reiche, S., & Riemer, T. G. (2024). Neuropsychological profiles of patients suffering from hallucinogen persisting perception disorder (HPPD): A comparative analysis with psychedelic-using and non-using controls. Scientific Reports, 14(1), 32159. https://doi.org/10.1038/s41598-024-82216-x
Marrocu, A., Kettner, H., Weiss, B., Zeifman, R. J., Erritzoe, D., & Carhart-Harris, R. L. (2024). Psychiatric risks for worsened mental health after psychedelic use. Journal of psychopharmacology (Oxford, England), 38(3), 225–235. https://doi.org/10.1177/02698811241232548
McAlpine, R. G., Blackburne, G., & Kamboj, S. K. (2024). Development and psychometric validation of a novel scale for measuring ‘psychedelic preparedness.’ Scientific Reports, 14(1), 3280. https://doi.org/10.1038/s41598-024-53829-z
McAlpine, R. G., Sacchet, M. D., Simonsson, O., Khan, M., Krajnovic, K., Morometescu, L., & Kamboj, S. K. (2024). Development of a digital intervention for psychedelic preparation (DIPP). Scientific Reports, 14(1), 4072. https://doi.org/10.1038/s41598-024-54642-4
McGuire, A. L., Cohen, I. G., Sisti, D., Baggott, M., Celidwen, Y., Devenot, N., Gracias, S., Grob, C., Harvey, I., Kious, B., Marks, M., Mithoefer, M., Nielson, E., Öngür, D., Pallas, A., Peterson, A., Schenberg, E. E., Summergrad, P., Waters, B., … Yaden, D. B. (2024). Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement. JAMA Network Open, 7(6), e2414650. https://doi.org/10.1001/jamanetworkopen.2024.14650
Nayak, S. M., White, S. H., Hilbert, S. N., Lowe, M. X., Jackson, H., Griffiths, R. R., Garcia-Romeu, A., & Yaden, D. B. (2024). Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study. Journal of Psychoactive Drugs, 1–10. https://doi.org/10.1080/02791072.2024.2346130
Nikitin, D., Mustafa, R. A., McQueen, B., Zemplenyi, A., DiStefano, M. J., Nhan, E., Kayali, Y., Richardson, M., Rind, D. M., Pearson, S. D., & Agboola, F. (2024). The effectiveness and value of midomafetamine-assisted psychotherapy for posttraumatic stress disorder. Journal of managed care & specialty pharmacy, 30(10), 1191–1195. https://doi.org/10.18553/jmcp.2024.30.10.1191
Noah, S., Shen, M., Erowid, E., Erowid, F., & Silver, M. (2024). A novel method for quantitative analysis of subjective experience reports: Application to psychedelic visual experiences. Frontiers in Psychology, 15, 1397064. https://doi.org/10.3389/fpsyg.2024.1397064
Noorani, T., & Liebert, R. J. (2024). Real-world evidence of the collective effects of psychedelic therapy: Evaluating from the grassroots. Journal of Psychedelic Studies. https://doi.org/10.1556/2054.2024.00369
Oliveira-Maia, A. J., Rive, B., Godinov, Y., & Mulhern-Haughey, S. (2024). Estimating the benefit of esketamine nasal spray versus real-world treatment on patient-reported functional remission: Results from the ICEBERG study. Frontiers in Psychiatry, 15, 1459633. https://doi.org/10.3389/fpsyt.2024.1459633
Olivieri, R., & Tófoli, L. F. (2024). Psychoanalysis and psychedelics: The censored story in Argentina. International Journal of Drug Policy, 133, 104596. https://doi.org/10.1016/j.drugpo.2024.104596
Ompad, D. C., Shrader, C.-H., Snyder, K. M., Netherland, J., Vakharia, S. P., & Walker, I. (2024). “He’s used drugs – he’s biased! He’s not a drug user – what would he know!”: A cross-sectional, online study of drug researchers’ experiential knowledge of drug use and disclosure. Drug and Alcohol Dependence Reports, 12, 100256. https://doi.org/10.1016/j.dadr.2024.100256
Palamar, J. J., Rutherford, C., & Keyes, K. M. (2024). Diversion of Undistributed Pharmaceutical Ketamine in the US. JAMA, 333(3), 252. https://doi.org/10.1001/jama.2024.23014
Peacock, C., Mascaro, J. S., Brauer, E., Zarrabi, A. J., Dunlop, B. W., Maples-Keller, J. L., Grant, G. H., Raison, C. L., Rab, F., & Palitsky, R. (2024). Spiritual health practitioners’ contributions to psychedelic assisted therapy: A qualitative analysis. PLOS ONE, 19(1), e0296071. https://doi.org/10.1371/journal.pone.0296071
Pendse, S. R., Kumar, N., & De Choudhury, M. (2024). Quantifying the Pollan Effect: Investigating the Impact of Emerging Psychiatric Interventions on Online Mental Health Discourse. Proceedings of the CHI Conference on Human Factors in Computing Systems, 1–22. https://doi.org/10.1145/3613904.3642477
Pierre, M. St., Standing, L., Herman, Y., Haden, M., & Walsh, Z. (2024). Patients’ Experiences Discussing Psychedelics for Therapeutic Purposes with Physicians and Other Health Care Providers. Psychedelic Medicine, 2(3), 161–165. https://doi.org/10.1089/psymed.2023.0060
Pop, I. A., Gielens, E., Kottmann, H., & Achterberg, P. (2024). Exploring the discourses around microdosing psychedelics within the r/microdosing online community. Social Science & Medicine, 347, 116702. https://doi.org/10.1016/j.socscimed.2024.116702
Poulin, J. M., Bigford, G. E., Lanctôt, K. L., Giacobbe, P., Schaffer, A., Sinyor, M., Rabin, J. S., Masellis, M., Singnurkar, A., Pople, C. B., Lipsman, N., Husain, M. I., Rosenblat, J. D., Cao, X., MacIntosh, B. J., & Nestor, S. M. (2024). Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression. Trials, 25(1), 441. https://doi.org/10.1186/s13063-024-08268-6
Rab, S. F., Raison, C. L., & Marseille, E. (2024). An estimate of the number of people with clinical depression eligible for psilocybin-assisted therapy in the United States. Psychedelics, 1–5. https://doi.org/10.61373/pp024r.0025
Robinson, O. C., Evans, J., Luke, D., McAlpine, R., Sahely, A., Fisher, A., Sundeman, S., Ketzitzidou Argyri, E., Murphy-Beiner, A., Michelle, K., & Prideaux, E. (2024). Coming back together: A qualitative survey study of coping and support strategies used by people to cope with extended difficulties after the use of psychedelic drugs. Frontiers in Psychology, 15, 1369715. https://doi.org/10.3389/fpsyg.2024.1369715
Robinson, O. C., Evans, J., McAlpine, R. G., Argyri, E. K., & Luke, D. (2024). An investigation into the varieties of extended difficulties following psychedelic drug use: Duration, severity and helpful coping strategies. Journal of Psychedelic Studies. https://doi.org/10.1556/2054.2024.00420
Rose, J. R. (2024). From Isolation to Social (and Psychedelic) Integration: A Sociology of Collective Effervescence and Therapeutic Community in Psychedelic‐Assisted Therapy. Sociology of Health & Illness, 47(1), e13872. https://doi.org/10.1111/1467-9566.13872
Rosenbaum, D., Hare, C., Hapke, E., Herman, Y., Abbey, S. E., Sisti, D., & Buchman, D. Z. (2024). Experiential Training in Psychedelic‐Assisted Therapy: A Risk‐Benefit Analysis. Hastings Center Report, 54(4), 32–46. https://doi.org/10.1002/hast.1602
Sakai, K., Bradley, E. R., Zamaria, J. A., Agin-Liebes, G., Kelley, D. P., Fish, A., Martini, V., Ferris, M. C., Morton, E., Michalak, E. E., O’Donovan, A., & Woolley, J. D. (2024). Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms. Psychopharmacology, 241(8), 1617–1630. https://doi.org/10.1007/s00213-024-06585-x
Sevigny, E. L., Thyssen, S., Erowid, E., & Lea, R. (2024). Misrepresentation of MDMA in the United States, 1999–2023. Drug and Alcohol Dependence, 264, 112467. https://doi.org/10.1016/j.drugalcdep.2024.112467
Spiers, N., Labate, B. C., Ermakova, A. O., Farrell, P., Romero, O. S. G., Gabriell, I., & Olvera, N. (2024). Indigenous psilocybin mushroom practices: An annotated bibliography. Journal of Psychedelic Studies, 8(1), 3–25. https://doi.org/10.1556/2054.2023.00297
Stanicic, F., Zah, V., Grbic, D., & De Angelo, D. (2024). Cost-effectiveness of midomafetamine-assisted therapy (MDMA-AT) in chronic and treatment-resistant post-traumatic stress disorder of moderate or higher severity: A health-economic model. PLOS ONE, 19(11), e0313569. https://doi.org/10.1371/journal.pone.0313569
Strickland, J. C., Garcia-Romeu, A., & Johnson, M. W. (2024). The Mystical Experience Questionnaire 4-Item and Challenging Experience Questionnaire 7-Item. Psychedelic Medicine, 2(1), 33–43. https://doi.org/10.1089/psymed.2023.0046
Stroud, J., Rice, C., Orsini, A., Schlosser, M., Lee, J., Mandy, W., & Kamboj, S. K. (2024). Perceived changes in mental health and social engagement attributed to a single psychedelic experience in autistic adults: Results from an online survey. Psychopharmacology, 242(2), 373–387. https://doi.org/10.1007/s00213-024-06685-8
Syed, O. A., Petranker, R., Fewster, E. C., Sobolenko, V., Beidas, Z., Husain, M. I., Lake, S., & Lucas, P. (2024). Preferences, Perceptions, and Environmental Considerations of Natural and Synthetic Psychedelic Substances: Findings from the Global Psychedelic Survey. Journal of Psychoactive Drugs, 1–11. https://doi.org/10.1080/02791072.2024.2446445
Thomann, J., Kolaczynska, K. E., Stoeckmann, O. V., Rudin, D., Vizeli, P., Hoener, M. C., Pryce, C. R., Vollenweider, F. X., Liechti, M. E., & Duthaler, U. (2024). In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin. Frontiers in Pharmacology, 15, 1391689. https://doi.org/10.3389/fphar.2024.1391689
Van Der Merwe, B., Rockefeller, A., Kilian, A., Clark, C., Sethathi, M., Moult, T., & Jacobs, K. (2024). A description of two novel Psilocybe species from southern Africa and some notes on African traditional hallucinogenic mushroom use. Mycologia, 116(5), 821–834. https://doi.org/10.1080/00275514.2024.2363137
Vanderijst, L., Hever, F., Buot, A., Dauré, C., Benoit, J., Hanak, C., Veeser, J., Morgiève, M., Campanella, S., Kornreich, C., Mallet, L., Leys, C., & Noël, X. (2024). Psilocybin-assisted therapy for severe alcohol use disorder: Protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial. BMC Psychiatry, 24(1), 77. https://doi.org/10.1186/s12888-024-05502-y
Véliz-García, O., & Domic-Siede, M. (2024). Latin American adults who regularly use macrodoses of psychedelics: A cross-sectional study. Scientific Reports, 14(1), 23921. https://doi.org/10.1038/s41598-024-74590-3
Vignando, M., Ffytche, D., Mazibuko, N., Palma, G., Montagnese, M., Dave, S., Nutt, D. J., Gabay, A. S., Tai, Y. F., Batzu, L., Leta, V., Williams Gray, C. H., Chaudhuri, K. R., & Mehta, M. A. (2024). Visual mismatch negativity in Parkinson’s psychosis and potential for testing treatment mechanisms. Brain Communications, 6(5), fcae291. https://doi.org/10.1093/braincomms/fcae291
Vohryzek, J., Cabral, J., Timmermann, C., Atasoy, S., Roseman, L., Nutt, D. J., Carhart-Harris, R. L., Deco, G., & Kringelbach, M. L. (2024). The flattening of spacetime hierarchy of the N,N -dimethyltryptamine brain state is characterized by harmonic decomposition of spacetime (HADES) framework. National Science Review, 11(5), nwae124. https://doi.org/10.1093/nsr/nwae124
Wells, A., Muthukumaraswamy, A. P. S., Morunga, E., Evans, W., Cavadino, A., Bansal, M., Lawrence, N. J., Ashley, A., Hoeh, N. R., Sundram, F., Applebaum, A. J., Parkinson, H., & Reynolds, L. (2024). PAM trial protocol: A randomised feasibility study of psychedelic microdosing–assisted meaning-centred psychotherapy in advanced stage cancer patients. Pilot and Feasibility Studies, 10(1), 29. https://doi.org/10.1186/s40814-024-01449-9
Whelan, T. P., Daly, E., Puts, N. A., Smith, P., Allison, C., Baron-Cohen, S., Malievskaia, E., Murphy, D. G. M., & McAlonan, G. M. (2024). The ‘PSILAUT’ protocol: An experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin. BMC Psychiatry, 24(1), 319. https://doi.org/10.1186/s12888-024-05768-2
Wolff, M., Evens, R., Mertens, L. J., Schmidt, C., Beck, J., Rutrecht, H., Cherniak, A. D., Gründer, G., & Jungaberle, H. (2024). Measuring psychotherapeutic processes in the context of psychedelic experiences: Validation of the General Change Mechanisms Questionnaire (GCMQ). Journal of Psychopharmacology, 38(5), 432–457. https://doi.org/10.1177/02698811241249698
Wood, M. J., McAlpine, R. G., & Kamboj, S. K. (2024). Strategies for resolving challenging psychedelic experiences: Insights from a mixed-methods study. Scientific Reports, 14(1), 28817. https://doi.org/10.1038/s41598-024-79931-w
Yates, G., & Melon, E. (2024). Trip-killers: A concerning practice associated with psychedelic drug use. Emergency Medicine Journal, 41(2), 112–113. https://doi.org/10.1136/emermed-2023-213377
Zech, J. M., Yaden, D. B., & Jones, G. M. (2024). Associations between psychedelic use and cannabis use disorder in a nationally representative sample. Drug and Alcohol Dependence, 266, 112502. https://doi.org/10.1016/j.drugalcdep.2024.112502
Preprints
Aboharb, F., Davoudian, P. A., Shao, L.-X., Liao, C., Rzepka, G. N., Wojtasiewicz, C., Indajang, J., Dibbs, M., Rondeau, J., Sherwood, A. M., Kaye, A. P., & Kwan, A. C. (2024). Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression. https://doi.org/10.1101/2024.05.23.590306
“Going beyond the head-twitch response? In this preprint now published in Nature Communications, Aboharb et al present a pipeline for drug classification using light sheet fluorescence microscopy and machine learning. Mice were given a large panel of drugs, including psilocybin, ketamine, 5-MeO-DMT, 6-fluoro-DET, MDMA, acute fluoxetine, chronic fluoxetine, and saline. Their models were able to distinguish between these drugs and they were further able to identify which brain regions were driving the predictions.” – S. Parker Singleton
“It’s always exciting to see a significant body of work that sets new standards in molecular and behavioral psychedelic neuroscience. This preprint is just that, providing clear demonstration of how a novel psychedelic characterization pipeline can sort compounds of varying psychoactive profiles. While we typically think of receptor-binding assays and behavioral paradigms traditionally dominating drug screening, here the authors have developed a unique approach by quantifying c-Fos expression and using machine learning models to capture the functional “footprint” of each compound across the entire brain. I always look forward to new publications from the Kwan lab, who are leaders in preclinical psychedelic research.” – Juliet Meccia
Blackburne, G., McAlpine, R. G., Fabus, M., Liardi, A., Kamboj, S. K., Mediano, P. A. M., & Skipper, J. I. (2024). Complex slow waves radically reorganise human brain dynamics under 5-MeO-DMT. https://doi.org/10.1101/2024.10.04.616717
“Pertaining to the field of psychedelics, this paper by Blackburne et al. is a landmark study. It represents the first comprehensive human neuroimaging analysis of 5-MEO-DMT, driving insights into how slow-frequency brain dynamics may contribute to the deconstruction of subjective experience. However, this study also has huge implications for cognitive neuroscience more broadly, opting to move beyond univariate analyses and instead characterising spatiotemporal profiles of neural activity, thus calling into question the putative theoretical mechanisms of psychedelic brain action. A must read for anyone interested in psychedelic neuroscience.” – Evan Lewis-Healey
Gordon, A. R., Carrithers, B. M., Pagni, B. A., Kettner, H., Marrocu, A., Nayak, S., Weiss, B. J., Carhart-Harris, R. L., Roberts, D. E., & Zeifman, R. J. (2024). The Effect of Psychedelics on Individuals with a Personality Disorder: Results from two Prospective Cohort Studies. https://doi.org/10.21203/rs.3.rs-4203641/v1
“While there is now considerable literature on the effects of psychedelics on personality, there has been much less attention to whether psychedelics can be useful for the impairments seen in individuals with personality disorders, who also tend to be screened out of clinical research trials. Personality impairment is a known predictor of poor outcomes with mental health treatment and can contribute to over-medicating individuals who struggle with these disorders. However, evidence from this preprint suggests that psychedelics could provide therapeutic benefit in this difficult-to-treat population. Psychedelic therapies may be uniquely well-suited for this kind of intervention given how they target processes like cognitive flexibility and emotion regulation that are related to personality function.” – David Mathai
Healy, C. J., Frazier, A., Kirsch, S., Sanford, A., Garcia-Romeu, A., Todman, M., Varon, J., & D’Andrea, W. (2024). Acute subjective effects of psychedelics in naturalistic group settings prospectively predict longitudinal improvements in trauma symptoms, trait shame, and connectedness among adults with childhood maltreatment histories. https://doi.org/10.31234/osf.io/3rbxe
“A few words on this article: it’s a naturalistic use study but as much a mechanisms study, it’s a research article but as much a theory article, and it’s a psychology article but as much an anthropology article. And a couple specific findings to highlight that could get missed amidst the main results: equivalent longitudinal therapeutic effects were observed from facilitated group ceremonies as from raves or other electronic dance music events, and drug dose predicted the intensity of acute subjective effects but not longitudinal therapeutic effects.” – CJ Healy
Pomrenze, M. B., Vaillancourt, S., Llorach, P., Rijsketic, D. R., Casey, A. B., Gregory, N., Salgado, J. S., Malenka, R. C., & Heifets, B. D. (2024). Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice. https://doi.org/10.1101/2024.03.03.583196
“This is a fascinating study. It would be interesting to explore whether activation of CeA PKCδ neurons interferes with other treatments, such as psychedelics, classical antidepressants, or electroconvulsive therapy, or if their permissive effect is specific to ketamine. More broadly, investigating how opioid receptors and other pharmacological targets outside NMDARs interact with ketamine’s antidepressant effects is valuable. Such insights could deepen our understanding of ketamine’s mechanism of action and its potential clinical interactions.” – Marc Duque Ramirez
Purple, R. J., Gupta, R., Thomas, C. W., Golden, C. T., Froudist-Walsh, S., & Jones, M. W. (2024). Short- and long-term reconfiguration of rat prefrontal cortical networks following single doses of psilocybin. https://doi.org/10.1101/2024.12.10.627734
“I thought this paper was brilliant. They found that psilocybin induces dose-dependent decreases in the firing rates of prefrontal pyramidal cells and interneurons, which supports some fantastic work from last year by Tyler Ekins on psychedelic-induced reductions in intrinsic excitability via potassium M-currents. They also provide evidence that psilocybin significantly reduces the entropy rate, and steepens the energy landscape of cortical dynamics, which contrasts with what a lot of people would have predicted. I think the increasingly sophisticated electrophysiology research in rodents may school us folk working on large-scale neuroimaging in humans.” – George Blackburne
The above publications received comments from the researchers we surveyed. Here are further 2024 publications that Michael included in his list.
***
Aday, J. S., Glynos, N., Baker, A., Pouyan, N., Barron, J., Herberholz, M., Kruger, D., Woolley, J., Boehnke, K. (2024). Major life changes following psychedelic use: A retrospective survey among people using psychedelics naturalistically. http://dx.doi.org/10.13140/RG.2.2.29745.80489
Aday, J. S., McAfee, J., Conroy, D. A., Hosanagar, A., Tarnal, V., Weston, C., Scott, K., Horowitz, D., Harte, S. E., Pouyan, N., Glynos, N. G., Baker, A. K., Guss, J., Davis, A. K., Burgess, H. J., Mashour, G. A., Clauw, D. J., & Boehnke, K. F. (2024). Preliminary Safety and Effectiveness of Psilocybin-Assisted Therapy in Adults with Fibromyalgia: An Open-Label, Pilot Clinical Trial. https://doi.org/10.31234/osf.io/j8zb5
Alberto-Silva, A. S., Hemmer, S., Bock, H. A., Alves Da Silva, L., Scott, K. R., Kastner, N., Bhatt, M., Niello, M., Jäntsch, K., Kudlacek, O., Bossi, E., Stockner, T., Meyer, M. R., McCorvy, J. D., Brandt, S. D., Kavanagh, P., & Sitte, H. H. (2024). Bioisosteric analogs of MDMA with improved pharmacological profile. https://doi.org/10.1101/2024.04.08.588083
Argyri, E. K., Evans, J., Luke, D., Michael, P., Michelle, K., Rohani-Shukla, C., Suseelan, S., Prideaux, E., McAlpine, R., Murphy-Beiner, A., & Robinson, O. (2024). Navigating Groundlessness: An interview study on dealing with ontological shock and existential distress following psychedelic experiences. https://doi.org/10.2139/ssrn.4817368
Askey, T., Allen-Ross, D., Lasrado, R., Gilmour, G., Hunt, S., Tamagnini, F., Ahmed, M., Stephens, G., & Maiarú, M. (2024). Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates the gabapentin-mediated analgesia. https://doi.org/10.21203/rs.3.rs-5026806/v1
Barnett, B. S. (2024). A survey investigating United States federal grant submissions proposing to investigate therapeutic applications of psychedelics. https://doi.org/10.1101/2024.10.12.24315367
Barnett, J. H., Todd, K. T., Benetatos, J., Rabichow, B. E., Gibson, K. A., Olney, K. C., & Fryer, J. D. (2024). Psilocybin causes sex, time, and dose dependent alterations in brain signaling pathways. https://doi.org/10.1101/2024.12.16.628764
Boltaev, U., Park, H. W., Brown, K. R., Delgado, M., Wu, J., Diaz-Pacheco, B. N., Botero Pinzon, M., He, K., Ahern, E., Goldshmid, N., Simpson, E. H., & Sames, D. (2024). Robust Methods For Quantifying Neuronal Morphology And Molecular Signaling Reveal That Psychedelics Do Not Induce Neuroplasticity. https://doi.org/10.1101/2024.03.04.583022
Bradshaw, A. J., Sharp, C., Van Der Merwe, B., Tremble, K., & Dentinger, B. T. M. (2024). Discovery of the closest free-living relative of the domesticated “magic mushroom” Psilocybe cubensis in Africa. https://doi.org/10.1101/2024.12.03.626483
Bréant, B. J. B., Mengual, J. P., Hoerder-Suabedissen, A., Patel, J., Bannerman, D. M., Sharp, T., & Vyazovskiy, V. V. (2022). Sleep-like state during wakefulness induced by psychedelic 5-MeO-DMT in mice. https://doi.org/10.1101/2022.12.11.519886
Brouns, E. J., Ekins, T. G., & Ahmed, O. J. (2024). Psychedelic enhancement of flexible learning weeks after a single dose. https://doi.org/10.1101/2024.12.17.629035
Brouwer, A., Brown, J. K., Erowid, E., Erowid, F., Thyssen, S., Raison, C. L., & Carhart-Harris, R. L. (2024). The Temporal Trajectory of the Psychedelic Mushroom Experience Mimics the Narrative Arc of the Hero’s Journey. https://doi.org/10.21203/rs.3.rs-3941205/v1
Brown, K. A., Ajibola, M. I., & Gould, T. D. (2024). Rapid Hippocampal Synaptic Potentiation Induced by Ketamine Metabolite ( 2R , 6R )-Hydroxynorketamine Persistently Primes Synaptic Plasticity. https://doi.org/10.1101/2024.10.18.619152
Bzdok, D., Carhart-Harris, R., Savignac, C., Bell, G., & Laureys, S. (2024). Large language models auto-profile conscious awareness changes under psychedelic drug effects. https://doi.org/10.21203/rs.3.rs-4670805/v1
Ching, T. H. W. (2024). A Primer for Culturally Attuned Psychedelic Research. https://doi.org/10.31234/osf.io/q8npu
Dai, R., Jang, H., Hudetz, A. G., Huang, Z., & Mashour, G. A. (2024). Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness. https://doi.org/10.1101/2024.10.23.619731
De La Fuente Revenga, M., & González-Maeso, J. (2024). Snapshot of 5-HT2A receptor activation in the mouse brain via IP1 detection. https://doi.org/10.1101/2024.10.11.617861
Dourron, H., Bradley, M., & Hendricks, P. (2024). Psychedelics’ Uncertain Risks: A Reply to Myran et al. https://doi.org/10.31234/osf.io/vujpk
Elsilä, L. V., Nagaeva, E., Luukkonen, J.-P., & Korpi, E. R. (2024). Effects of serotonin agonists LSD and 25CN-NBOH on conditioned place preference and on synaptic plasticity of VTA dopamine neurons in mice. https://doi.org/10.1101/2024.12.12.628157
Fleury, S., & Nautiyal, K. M. (2024). The non-hallucinogenic serotonin 1B receptor is necessary for the antidepressant-like effects of psilocybin in mice. https://doi.org/10.1101/2024.10.18.618582
Fort, L. D., Costines, C., Wittmann, M., Demertzi, A., & Schmidt, T. T. (2024). Classification Schemes of Altered States of Consciousness. https://doi.org/10.31234/osf.io/pmuqt
Glynos, N. G., Huels, E. R., Nelson, A., Kim, Y., Kennedy, R. T., Mashour, G. A., & Pal, D. (2024). Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N -dimethyltryptamine in Rats. https://doi.org/10.1101/2024.04.19.589047
Gudmundsen, F., Czurylo, J., Vo, C. T., Ruuska, J., Jessen, N. S., Baun, C., Herth, M. M., Shalgunov, V., Fisher, P. M., & Palner, M. (2024). Not all serotonergic psychedelics are alike—They induce distinct patterns of altered metabolic activity and connectivity. https://doi.org/10.31219/osf.io/mq4v2
Hodge, A.-L., Forsyth, A., Noorani, T., Muthukumaraswamy, S., Rolleston, A., & McHugh, P. (2024). Tū Wairua: Development of an Indigenous Rongoā Māori Approach to Healing with Psilocybin Containing Mushrooms. https://doi.org/10.31234/osf.io/93x5h
Horrocks, M., Mohn, J. L., & Jaramillo, S. (2024). The serotonergic psychedelic DOI impairs deviance detection in the auditory cortex. https://doi.org/10.1101/2024.09.06.611733
Hoyer, D. (2024). On serotonin, psychedelics, entactogens and psychoplastogens in depression, anxiety, post-traumatic stress, and related disorders. https://doi.org/10.22541/au.171648613.31141136/v1
Huang, Z., Wei, X., Wang, Y., Tian, J., Dong, J., Liang, B., Lu, L., & Zhang, W. (2024). Psilocybin Promotes Cell-Type-Specific Changes in the Orbitofrontal Cortex Revealed by Single-Nucleus RNA-seq. https://doi.org/10.1101/2024.01.07.573163
Ippolito, A., Vasudevan, S., Hurley, S., Gilmour, G., Westhorpe, F., Churchill, G., & Sharp, T. (2024). Increased 5-HT2A receptor signalling efficacy differentiates serotonergic psychedelics from non-psychedelics. https://doi.org/10.1101/2024.06.13.594677
Jensen, A. A., Cecchi, C. R., Hibicke, M., Bach, A. H., Kaadt, E., Märcher-Rørsted, E., Nichols, C. D., Elfving, B., & Kristensen, J. L. (2024). The selective 5-HT2A receptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents. https://doi.org/10.1101/2024.04.19.590212
Jensen, M. E., Stenbæk, D. S., Messell, C. D., Poulsen, E. D., Varga, T. V., Fisher, P. M., Nielsen, M. K. K., Johansen, S. S., Volkow, N. D., Knudsen, G. M., & Fink-Jensen, A. (2024). Single-Dose Psilocybin Therapy for Alcohol Use Disorder: Pharmacokinetics, Feasibility, Safety, and Efficacy in an Open-Label Study. https://doi.org/10.21203/rs.3.rs-4947184/v1
Kangaslampi, S., & Lietz, M. P. (2024). Psychedelics and autobiographical memory – Six open questions. https://doi.org/10.31234/osf.io/su7ch
Klučková, T., Nikolič, M., Tylš, F., Viktorin, V., Vejmola, Č., Viktorinová, M., Bravermanová, A., Androvičová, R., Andrashko, V., Korčák, J., Zach, P., Hájková, K., Kuchař, M., Balíková, M., Brunovský, M., Horáček, J., & Páleníček, T. (2024a). The phenomenology of psilocybin’s experience mediates subsequent persistent psychological effects independently of sex, previous experience or setting. https://doi.org/10.1101/2024.08.26.24311611
Kugel, J. M., Laukkonen, R. E., Yaden, D. B., Yucel, M., & Liknaitzky, P. (2024). Insights on Psychedelics: A Systematic Review of Therapeutic Effects. https://doi.org/10.31219/osf.io/5en4u
Larsen, K., Lindberg, U., Ozenne, B., McCulloch, D. E., Armand, S., Madsen, M. K., Johansen, A., Stenbæk, D. S., Knudsen, G. M., & Fisher, P. M. (2024). Acute psilocybin and ketanserin effects on cerebral blood flow: 5-HT2AR neuromodulation in healthy humans. https://doi.org/10.1101/2024.09.19.24313958
Lewis-Healey, E., Pallavicini, C., Cavanna, F., & D’Amelio, T. (2024). Time-resolved neural and experience dynamics of medium- and high-dose DMT. https://doi.org/10.1101/2024.12.19.629418
Lii, T. R., Flohr, J. R., Okada, R. L., Cianfichi, L. J., Hack, L. M., Schatzberg, A. F., & Heifets, B. D. (2024). Opioids Diminish the Placebo Antidepressant Response: A Post Hoc Analysis of a Randomized Controlled Ketamine Trial. https://doi.org/10.1101/2024.09.24.24314243
Lyons, T., Spriggs, M., Kerkelä, L., Rosas, F., Roseman, L., Mediano, P., Timmermann, C., Oestreich, L., Pagni, B., Zeifman, R., Hampshire, A., Trender, W., Douglass, H., Girn, M., Godfrey, K., Kettner, H., Sharif, F., Espasiano, L., Gazzaley, A., … Carhart-Harris, R. (2024). Human brain changes after first psilocybin use. https://doi.org/10.1101/2024.10.11.617955
Majic, T., Schmidt, T. T., Gröticke, A., Gasser, P., Richards, W. A., Riemer, T. G., & Evens, R. (2024). The Afterglow Inventory (AGI) – validation of a new instrument for measuring subacute effects of classic serotonergic psychedelics. https://doi.org/10.31234/osf.io/s6bzc
Mallaroni, P., Singleton, P., Mason, N. L., Satterthwaite, T. D., & Ramaekers, J. G. (2024). The forgotten psychedelic: Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin. https://doi.org/10.1101/2024.10.22.619393
Marinis, J., Clarke, S. T., & Bedi, G. (2024). Methodological issues undermine evidence about adverse effects of psilocybin-assisted psychotherapy. https://doi.org/10.31234/osf.io/4bk2p
McGovern, H., Bajo, L., Hassed, G., Hoefnagels, R., Levy, M., Rose, N., De Foe, A., & Hutchinson, B. (2024). Deconstructing Psychedelic Phenomenology: A thematic analysis of discrete phases of the psychedelic experience. https://doi.org/10.31234/osf.io/95qgt
McGovern, H., Wellman, N., Hutchinson, B., Oestreich, L., Cooper, S. E., Fonzo, G., & Doss, M. (2024). Resetting the Hippocampal Buffer: A Neurocognitive Account of Psychedelic Therapy for Anxiety-Related Psychopathology. https://doi.org/10.31234/osf.io/y8sb7
Netzer, O., Magal, N., Stern, Y., Polinsky, T., Gross, R., Admon, R., & Salomon, R. (2024). Trauma Under Psychedelics: MDMA Shows Protective Effects During the Peritraumatic Period. https://doi.org/10.1101/2024.03.28.587237
Nikolic, M., Mediano, P., Froese, T., Reydellet, D., & Palenicek, T. (2024). Psilocybin alters brain activity related to sensory and cognitive processing in a time-dependent manner. https://doi.org/10.1101/2024.09.09.24313316
Pasquini, L., Simon, A. J., Gallen, C. L., Kettner, H., Roseman, L., Gazzaley, A., Carhart-Harris, R. L., & Timmermann, C. (2024). Dynamic medial parietal and hippocampal deactivations under DMT relate to sympathetic output and altered sense of time, space, and the self. https://doi.org/10.1101/2024.02.14.580356
Pasquini, L., Vohryzek, J., Escrichs, A., Sanz Perl, Y., Ponce-Alvarez, A., Idesis, S., Girn, M., Roseman, L., Mitchell, J. M., Gazzaley, A., Kringelbach, M., Nutt, D. J., Lyons, T., Carhart-Harris, R. L., & Deco, G. (2024). Long-term effects of psilocybin on dynamic and effectivity connectivity of fronto-striatal-thalamic circuits. https://doi.org/10.1101/2024.11.06.622302
Piccinini, J. I., Perl, Y. S., Pallavicini, C., Deco, G., Kringelbach, M., Nutt, D., Carhart-Harris, R., Timmermann, C., & Tagliazucchi, E. (2024). Transient destabilization of whole brain dynamics induced by DMT. https://doi.org/10.1101/2024.01.26.577435
Pomrenze, M. B., Vaillancourt, S., Salgado, J. S., Raymond, K. B., Llorach, P., Touponse, G. C., Pinto, D. F. C., Rastegar, Z., Casey, A. B., Eshel, N., Malenka, R. C., & Heifets, B. D. (2024). 5-HT2C receptors in the nucleus accumbens constrain the rewarding effects of MDMA. bioRxiv, 2024.10.20.619256. https://doi.org/10.1101/2024.10.20.619256
Pronovost-Morgan, C., Greenway, K., & Roseman, L. (2024). The Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) Guidelines: An international Delphi consensus study. https://doi.org/10.21203/rs.3.rs-5428217/v1
Rogers, S. A., Heller, E. A., & Corder, G. (2024). Psilocybin-enhanced fear extinction linked to bidirectional modulation of cortical ensembles. https://doi.org/10.1101/2024.02.04.578811
Sanders, J. W., Millière, R., Daily, Z. G., Carhart-Harris, R., & Timmermann, C. (2024). DMT micro-phenomenology. https://doi.org/10.31234/osf.io/2m9d4
Schenberg, E. E. (2024). From efficacy to effectiveness: Evaluating psychedelic randomised controlled trials for trustworthy evidence-based policy and practice. https://doi.org/10.31234/osf.io/uxhv7
Schmidt, M., Hoffrichter, A., Davoudi, M., Horschitz, S., Lau, T., Meinhardt, M., Spanagel, R., Ladewig, J., Köhr, G., & Koch, P. (2024). Psilocin Fosters Neuroplasticity in IPSC-Derived Human Cortical Neurons. https://doi.org/10.21203/rs.3.rs-4242829/v2
Scholkmann, F., & Sjöstedt-Hughes, P. (2024). Psychosomadelics: The case for renaming psychedelics. https://doi.org/10.31234/osf.io/3j2kc
Shao, L.-X., Liao, C., Davoudian, P. A., Savalia, N. K., Jiang, Q., Wojtasiewicz, C., Tan, D., Nothnagel, J. D., Liu, R.-J., Woodburn, S. C., Bilash, O. M., Kim, H., Che, A., & Kwan, A. C. (2024). Pyramidal cell types and 5-HT2A receptors are essential for psilocybin’s lasting drug action. https://doi.org/10.1101/2024.11.02.621692
Shore, R., Dobson, K., Thomson, N., Barnim, N., Bergman, H., Rideout, K., McKeown, S., Olmstead, M. C., Goldie, C., & Dumont, E. (2024). Behavioural Investigations of Psilocybin in Animals 1962-2021: A Scoping Review. https://doi.org/10.1101/2024.01.04.574146
Stein, M. V., & Terhune, D. B. (2024). Suggestions effects in psychedelics: Confounds and opportunities. https://doi.org/10.31234/osf.io/5krs4
Suay, D., Aicher, H. D., Kometer, M., Mueller, M. J., Caflisch, L., Hempe, A., Steinhart, C. P., Elsner, C., Wicki, I. A., Müller, J., Meling, D., Dornbierer, D. A., Scheidegger, M., & Bottari, D. (2024). Ayahuasca-Inspired DMT/HAR Formulation Reduces Brain Differentiation Between Self and Other Faces. https://doi.org/10.1101/2024.10.28.24316308
Vella, Y., Syrova, K., Petruskova, A., Koutrouli, I., Kutna, V., Pala, J., Nikolic, M., Sichova, K., Mazoch, V., Jurok, R., Kuchar, M., Bendova, Z., & Palenicek, T. (2024). Effects of serotonergic psychedelics on synaptogenesis and immediate early genes expression—Comparison with ketamine, fluoxetine and lithium. https://doi.org/10.1101/2024.08.07.606965
Vohryzek, J., Luppi, A., Atasoy, S., Deco, G., Timmermann, C., Carhart-Harris, R. L., & Kringelbach, M. L. (2024). Time-resolved coupling between connectome harmonics and subjective experience under the psychedelic DMT. https://doi.org/10.1101/2024.05.30.596410
Stay Informed in 2025 with Pα+
Subscribe to Pα+ to receive all of our Bulletins, deep dives and analysis, as well as access to the Pα+ Library and other subscriber-only content.
Your subscription goes directly toward supporting our coverage, not glossy graphic design or marketing budgets. Learn more and subscribe here, or get in touch to discuss team plans.
Ready to subscribe to Pα+? Choose a monthly or annual plan by clicking the appropriate button below.
Looking for team/group plans? Email plus@psychedelicalpha.com.
- A significant jump from last year, and only one out of every twelve of them was a review of psilocybin for the treatment of depression (a slight exaggeration).
- Here’s a small collection of some of my favourite case reports (Federico et al., Wahba et al.), individual chapters (Holze et al., Thomas, Evans et al., Koslowski et al., and many others from the currently unnamed Current Topics in Behavioral Neurosciences book focused on psychedelic harm reduction), whole academic textbooks (Philosophical Perspectives on Psychedelic Psychiatry, The Palgrave Handbook of Philosophy and Drug Use), and dissertations/theses (Breeksema, Ona).
- One declined to participate because they do not work in the field of psychedelics, stating that “substituted amphetamines are NOT psychedelics.”
