This October, we saw two significant psychedelic studies being published that were previously released as pre-prints. The first is concerned with the extended DMT trial (also see Blossom’s April Recap), and the second investigates the antidepressant effects of ketamine when given to patients under anaesthesia (also see Blossom’s May Recap).
Next to these studies, a good mix of surveys highlights both the potential of psychedelics and the risks involved. Acutely, many people reported feelings of shame and guilt during the trip, whilst after a trip, a third of recreational users who had a challenging experience reported extended difficulties up to a year later. Still, the use of psychedelics might enhance someone’s meditative practice.
October was another fruitful month for psychedelic research, with 26 articles (and full summaries for paying members) added to the database (nearing 2000 articles). In this recap, I also cover ego dissolution, affordability of treatments, and integration guidelines.
Leaving Reality Behind, Two Distinct Trials
Psychedelic research serves several different outcomes. One line of thought is concerned directly with the applicability of the research findings to clinical practice. Is it effective? Can we make it affordable? Another line investigates scientific questions, the big ‘what if’ questions (without direct regard for practical outcomes). Two studies along the second line were recently published (after being out in pre-print – before peer review – in April and May).
The first deals with the extended effects of DMT in healthy participants. It asks what will happen to them and tests the infusion protocol. On both accounts, the “Psychological and physiological effects of extended DMT” study is a success, reporting that the volunteers safely navigated the changed psychological landscape in an intense trip that lasted half an hour longer than the typical DMT trip.
Changing the paradigm from a very intense trip to none at all is the triple-masked ketamine under anaesthesia study. In this study, participants who were undergoing routine surgery were given either ketamine or a placebo whilst under general anaesthesia. The researchers argue that this was able to filter out the acute/psychological effects of ketamine and thus provide a ‘cleaner’ picture of the physiological effects alone.
Still, many researchers chimed in, and many discussions erupted on Twitter/X. One thing that stood out is the large positive effect seen in both arms (there was no difference between the placebo and ketamine arms of the study). This, once again, shows the vast role that expectancy effects play in (psychedelic) research/treatment.
Psychedelic Surveys of October 2023
Recently, there has been a heightened emphasis on the adverse effects of psychedelics. After a barrage of positive news, the balance shifts towards the other side. And this isn’t without reasons. A survey on extended difficulties finds that of those who had experienced negative effects after psychedelics (so a subsection of all users), a third of them still experienced these adverse effects a year later. Those who had experienced negative outcomes in a guided setting or with a lower dose were less likely to experience negative effects long-term.
Investigating the psychiatric risks of psychedelics, a survey of over 2800 people (of which 20% used psychedelics) finds a correlation between psychedelic use and more unusual visual experiences. Of those who used psychedelics, 1.3% had been told by a doctor that they suffered from HPPD.
A longitudinal study looked at the effects of psilocybin use on feelings of shame and guilt in a naturalistic setting. The research found that while most participants reported positive psilocybin experiences, acute feelings of shame or guilt during the trip were common, occurring in 68% of users. The ability to constructively work through these difficult emotions was linked to greater well-being after psilocybin use. On average, psilocybin resulted in a small but significant decrease in trait shame that lasted 2-3 months. However, for a substantial minority of participants (30%), trait shame increased following psilocybin use.
Another longitudinal study investigated associations between psychedelic use and meditation practices in the US and UK. The research found that psychedelic use over two months was linked to increased engagement with mindfulness meditation. Additionally, having more profound insights during a psychedelic experience was associated with greater involvement in both mindfulness and loving-kindness/compassion meditation practices. An interesting finding was that more engagement with loving-kindness/compassion meditation at baseline was connected to reduced severity of challenging experiences during subsequent psychedelic use.
Bringing these threads together, a survey of people who experienced adverse childhood experiences finds that there is a high interest in the use of psilocybin (therapy) to treat psychological distress.
The Variety of Ketamine Studies – From Affordability to Quetiapine
An open-label phase IIIb trial compared esketamine plus an antidepressant to quetiapine plus an antidepressant for treatment-resistant depression (TRD). The esketamine group had significantly higher remission rates at week 8 (27.1% vs 17.6%) and lower relapse rates through week 32 after remission. Adverse events were consistent with the known safety profiles. This suggests that esketamine may be more effective for achieving and sustaining remission in treatment-resistant depression.
A randomized pilot study looked at how ketamine affects functional connectivity between the amygdala and medial prefrontal cortex (mPFC) in people with PTSD. Contrary to expectations, ketamine did not increase connectivity but caused a transient decrease in vmPFC-amygdala connectivity. This challenges previous assumptions and indicates a need for further research into dissociative states’ neurobiological basis in PTSD.
In an open-label study of esketamine nasal spray for TRD, patients reported early improvements in depression, anhedonia, and suicidality that were sustained over three months, while clinicians noted varying improvements at different time points. This study highlights the value of patient perspectives in evaluating psychedelic therapies.
A placebo-controlled study found ketamine’s effects on negative emotional states are mediated through distinct altered states it produces. Higher depersonalization relieved negative brain activity, while dissociative amnesia exacerbated insula activation. This suggests specific dissociative states differentially impact ketamine’s antidepressant response.
An analysis of IV ketamine for TRD found later depression onset positively correlated with better treatment response, indicating earlier onset may limit ketamine efficacy due to reduced neuroplasticity. Other factors like age, sex, and dissociation did not predict response, highlighting onset timing’s significance.
Finally, an economic analysis argues systemic reforms are needed to prevent patented, costly psychedelic formulations like esketamine from dominating over generic options. Commercial incentives, public funding, and reduced regulatory barriers are essential to enable affordable access to psychedelic therapies.
All Other Psychedelic Studies of October 2023
With 26 articles added (and 60 more in Blossom’s link overview), there is too much to talk about in detail, so here is a quick primer on the other studies:
- A systematic review of MDMA’s effects on sexual function found it increased desire but had mixed impacts on arousal and erectile function in men and women. Both genders experienced delayed but more intense orgasms.
- A re-analysis of an LSD neuroimaging study found it increased functional connectivity between sensory thalamus nuclei and cortices but decreased striatal-thalamic connectivity.
- Reviewing the evidence on psilocybin-assisted therapy, researchers find it significantly reduces depressive symptoms, but more research is needed on safety and optimization.
- A neuroimaging study found psilocybin caused individualized changes in cerebral blood flow depending on a person’s brain state and subjective psychedelic experience.
- Psilocybin microdosing and neurofeedback are combined in a feasibility study. It finds significant self-reported improvements in daily executive functions like working memory and inhibition.
- New proposed guidelines offer practical insights for mental health professionals on integrating psychedelic experiences, covering theoretical foundations, models, and interventions.
- A philosophical piece discusses how mystical experiences from psychedelics may align with naturalism but verification of metaphysical claims about reality remains challenging.
- A review of fMRI studies on psychedelics found methodological limitations but shared findings of altered connectivity in sensorimotor and prefrontal regions.
- A conceptual article focuses on psychedelics’ ego effects through regression, suggesting lasting change requires targeting core ego patterns psychodynamically.
- Repeated ayahuasca use is linked to cortical structural changes correlated with 5-HT2A and receptor gene expression alterations.
- An analysis found psilocybin dose and age predicted challenging trip experiences, while personality traits had minimal impact.
- A preclinical study showed repeated low-dose psilocybin (akin to microdosing) imparted resilience, reduced compulsiveness, and strengthened cortical-thalamic connections in rats.
- Researchers found links between ADHD symptoms and lifetime use of various psychoactive substances, including
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