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Psychedelic Research Bulletin: September 2021

September brought nearly 30 new and exciting papers on psychedelics. Some publications focus on their safety, such as one that looks at LSD in clinical settings. Well-being after the ceremonial or therapeutic use of psychedelics and ego-dissolution as a possible mechanism is also explored.

We also learned more about the action of the atypical psychedelic salvinorin-A. The use of ‘magic mushrooms’ in the US population is explored, and we learn how open psychologists are to psychedelic-assisted therapies.

Differences in Psychedelic use in the clinic vs. general population

People in the United States use psilocybin-containing mushrooms to self medicate for reasons related to mental health, with users reporting significantly higher levels of anxiety and depression, and lower quality of life than the average. This finding stands in direct contrast to the narrative that psychedelics lead to more positive mental health outcomes, though there are many confounding factors if we only look at a snapshot in a survey (e.g., those with mental health issues are more likely to try psychedelics).

This is also found when another survey looked at the use of MDMA in those with PTSD and substance use disorder (SUD). It was found that SUD patients with PTSD were more likely to use MDMA than those without PTSD and MDMA use was associated with avoidance symptoms. The authors conclude that MDMA use might reflect an attempt to self-medicate to deal with avoidance symptoms, however, it may also be the case that MDMA use led to more severe avoidance symptoms.

The use of psychedelics, without the container of therapy, can be more unpredictable and less therapeutic. In contrast to the two above articles, a review finds that MDMA-assisted therapy could help treat the symptoms of social anxiety disorder (SAD). Disruptions in neurological, perceptual, receptive, and expressive systems regulating social behavior in SAD may take place as a result of MDMA-assisted therapy.

Using psychedelics outside of clinical settings can be challenging as 23 ‘underground’ practitioners report on the unique challenges faced in that context. The interview study reports on the themes identified that range from descriptive (e.g. use of touch) and prescriptive (e.g. grounding) ethical challenges. With recent accusations against some practitioners, the substantial challenges also faced by patients should not be underestimated.

Psychedelics lead to ego dissolution

If you’ve been reading about psychedelics for some time, you might have come across the term ‘ego dissolution‘. Also called ‘ego death,’ the term stands for the complete loss of subjective self-identity, the lack of feeling like a ‘self’ or ‘I’. A theory-building article tackles this subject head-on and argues that although these selfless states of consciousness are rare, they reveal normally congruent processes of self-modelling which demonstrate the principle that phenomenal models of the self ‘shape’ the subjectivity of our experiences.

How this actually happens in the brain is further investigated in a pre-print article that finds that 5-HT2A receptor (the serotonin receptor psychedelics are so fond of) agonism, at the top of the cortical hierarchy, leads to both ego dissolution and long-term neural plasticity. Whether this plasticity may be used to lead to positive mental health outcomes is further investigated in a novel framework that proposes psychedelics may reopen “critical periods” in neurodevelopment whereby the brain is particularly sensitive (neuroplasticity) to environmental input.

Psychedelics can lead us to focus less on the outward-focused aspects of self (identity) and this effect was mediated by ego dissolution (and the intensity of mystical experiences) finds a survey study. The participants in the study also reported higher positive emotional reactivity.

Psychedelics disturb the stability of thought and conscious experience (e.g., dissolving the idea of an ego), and a recent review argues that we should also study this in specific regions of the brain (versus whole-brain models). In doing so, we may get a better grip on which area of the brain ‘generates’ different parts of conscious experience.

Well-being after different psychedelics

An open-label study with 30 participants looked at the improvements in well-being, healthy functioning (in society), depression, and suicidality ratings. Although a quarter of the participants did report healthy well-being, the effect was smaller than that on scores of depression and suicidality. Changes on those two domains may be necessary yet not sufficient for restoration to well-being.

A week after an ayahuasca ceremony, participants reported increased well-being, cognitive empathy, and less neuroticism. A single dose of ayahuasca was found to have these positive effects in an observational study. The study also found an enhanced ability to take an objective and non-judging stance towards the self (decentering), harkening back to the ego dissolution papers profiled above. As with many studies with ayahuasca, this study was conducted at a ceremony. With a new protocol on freeze-drying ayahuasca, we may be closer to also study it in clinical settings.

Integrating psychedelic experiences is, as far as we now know, vital for positive outcomes. This perspective is confirmed by ayahuasca ceremony leaders who were interviewed about their views on preparation, integration, and what could go wrong in those processes. Another group that will have a large impact on the well-being of those using psychedelics are psychologists. A survey among them found cautiously optimistic attitudes toward psychedelics as medicines.

The rest of the studies in September 2021

case study from 1959 where psilocybin was used in the treatment of anorexia has recently been translated. Imperial College London is currently recruiting patients for the first modern study of psilocybin-assisted therapy for anorexia.

Multiple review articles have taken a look at the existing literature and conclude that 1) serotonergic psychedelics appear to be effective and safe in improving symptoms of anxiety and depression, and 2) that we have relatively sparse data on neuropsychological function after psychedelics use, especially for psilocybin.

A number of synthetic psychoactive drugs show activity on the serotonin receptor 5-HT7R (in mice), prompting authors to argue that this could be a potential target for treating autism. This is in contrast to, as detailed in a meta-analysis of brain imaging studies, to 5-HT1a/2a receptor activity observed with most psychedelics.

Another area where psychedelics show promise is in the treatment of neurodegenerative disorders (e.g., Alzheimer’s). Psychedelics may act as modulators of the immune system by reducing levels of pro-inflammatory biomarkers.

Finally, a hypothesis paper argues for four factors that may have contributed to (early) humans including psychedelics in their diet: 1) management of psychological distress, 2) enhanced social interactions, 3) facilitation of collective rituals, and 4) enhanced group decision making.

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