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Psychedelic Research Recap October 2024

Published October 28, 2024

Psychedelic Research Recap October 2024

Welcome back to our monthly update on psychedelic research!

In October, psychedelic research spans from clinical applications to fundamental neuroscience. Studies provide new insights into how MDMA and psilocybin affect personality and mental health while also examining the often-overlooked psychedelic 2C-B. Three studies examine the mechanisms behind psychedelics’ therapeutic effects, from their influence on cell membranes to their impact on brain connectivity patterns.

The research this month places special emphasis on how subjective experiences during psychedelic sessions relate to therapeutic outcomes, with studies examining psychological flexibility, empathy, and emotional breakthroughs. We also see innovative approaches emerging, including the combination of psilocybin with neurofeedback, and important findings regarding antidepressant discontinuation before psychedelic therapy.

This month’s recap is made possible by our supporting members.

Check out the research link overview for all the studies we didn’t add to the database.

Therapeutic Applications of Psychedelics

A notable study this month looked at whether stopping antidepressants before psilocybin therapy affects its success in treating hard-to-treat depression. Looking at 233 patients from the Compass Phase IIb trial, researchers found that those who stopped their antidepressants during screening had similar results to those who started the trial without medications. This shows that recently stopping antidepressants doesn’t seem to reduce how well psilocybin works or change the psychedelic experience itself.

A meta-analysis of 31 studies examined how much the subjective effects of ketamine and psilocybin matter for their therapeutic benefits in depression and substance use disorders (SUD). The analysis found these subjective experiences play a modest but important role – psilocybin’s effects explained about 24% of the therapeutic benefits, while ketamine’s effects explained 5-10%. The connection between subjective effects and outcomes was stronger for both drugs when treating addictions (SUDs) compared to depression.

Looking at MDMA, a placebo-controlled trial with 34 healthy adults tested how a single dose (100mg) affects personality and emotions. While the main results weren’t statistically significant, researchers found meaningful increases in openness to experience and positive emotions 48 hours after taking MDMA compared to placebo.

An online survey explored how psychedelics affect autistic adults, with 233 participants describing their most impactful psychedelic experience. Most reported feeling less psychological distress (82%) and social anxiety (78%), and being more socially engaged (70%) afterwards. However, 20% had some adverse effects, like increased anxiety. The improvements were most strongly linked to gaining more psychological flexibility rather than the intensity of the psychedelic experience itself.

Mental Processes Behind Psychedelic Benefits

Several studies this month looked at how psychedelics affect our thoughts, emotions, and social connections.

A survey with 457 people explored how psychedelics change unhelpful thinking patterns and improve well-being. The study found that shifts in these thought patterns after psychedelic use had a bigger impact on well-being than the intensity of mystical or challenging experiences during the trip. However, emotional breakthroughs during the experience were particularly important for positive changes.

Another survey with 629 psychedelic users examined how these substances affect psychological flexibility – our ability to adapt and respond well to life’s challenges. The results showed that having meaningful insights during psychedelic experiences was strongly linked to greater acceptance, a key part of psychological flexibility. Importantly, the quality of individual psychedelic experiences mattered more than how often someone used them.

A meta-analysis looking at how classic psychedelics affect empathy brought together data from five studies testing LSD, psilocybin, and ayahuasca. Using a standardized empathy test, the analysis found these substances significantly increased emotional empathy – both automatic emotional responses and conscious feelings toward others. However, they didn’t affect cognitive empathy (the ability to understand others’ emotions). This suggests psychedelics mainly boost the emotional side of connecting with others rather than changing how we think about others’ feelings.

Brain Science Behind Psychedelics

A lab study revealed that the psychedelic DOI affects cell membranes much more strongly than serotonin – it’s over 100 times better at changing how cell membranes work. DOI makes membranes more fluid and helps small structures merge with cells. This suggests psychedelics might work not just by binding to receptors as we thought, but also by physically changing how cell membranes function and form new connections.

Mouse research found that a specific receptor (serotonin 1B) is needed for psilocybin’s antidepressant effects, separate from the receptor that causes hallucinations. When mice lacking this receptor got psilocybin, they didn’t show the usual improvements in depression-like behaviours. This points to a new way psilocybin might help with depression, possibly without requiring the intense psychedelic experience.

An EEG study with 29 people examined how 5-MeO-DMT changes brain activity. The drug dramatically alters slow brain waves, making them more chaotic and less organized than normal. It also slows and stabilizes overall brain activity, with fewer rapid shifts between different states. These changes might explain why 5-MeO-DMT creates such profound changes in how people experience time, space, and self.

The Other Psychedelic Studies from October 2024

In addition to the studies we’ve discussed, here is a brief recap of two more novel studies. A pre-print brain imaging study comparing 2C-B and psilocybin found that both substances reduced connectivity within brain networks while increasing connections between different networks. However, 2C-B showed milder effects than psilocybin and unique patterns of connectivity in certain brain regions. The findings suggest 2C-B could be a promising therapeutic tool since it produces similar brain changes to psilocybin but with less intense subjective effects and anxiety.

A feasibility study testing psilocybin microdoses combined with neurofeedback training found that while participants didn’t show objective improvements in executive function tasks, they reported notable gains in daily cognitive abilities like working memory and mental flexibility. This study demonstrates that combining microdosing with neurofeedback is practical and well-tolerated, though more rigorous research is needed to confirm its benefits.

Papers Published in October 2024

13 studies from the Blossom database published this month.

Acute Psychedelic Reactions, Post-Acute Changes in Dysfunctional Attitudes, and Psychedelic-Associated Changes in Wellbeing

Journal of Psychoactive Drugs· Oct 30, 2024· Earleywine, M., Falabella, G. S., Low, F. et al.

This survey study (n=457) explores the relationship between dysfunctional attitudes and well-being in the context of psychedelic-assisted therapy. It finds that post-acute changes in these attitudes significantly influence well-being, with emotional breakthroughs having a greater impact than challenging or mystical experiences.

Effects of a Serotonergic Psychedelic on the Lipid Bilayer

ACS Chemical Neuroscience· Oct 23, 2024· Huster, D., Maiti, S., Mote, K. R. et al.

This lab study used different ways of looking at cells to see how the psychedelic drug DOI affects the outer layer of cells (lipid membrane). The study found that DOI is over 100 times stronger than serotonin at disrupting the cell's outer layer, helping small bubble-like structures combine with cells, and making it easier for tiny holes to form in cell membranes. This suggests that psychedelics might affect the brain not just by binding to receptors (their usual known method), but also by physically changing how cell membranes work and help create new connections.

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· Oct 23, 2024· Dunlop, B. W., Hyatt, C. S., Maples-Keller, J. L. et al.

This pre-registered randomised placebo-controlled study (n=34) investigates the effects of MDMA (100mg) administration on personality traits and affective states in healthy adults. While no statistical significance was found for the primary hypotheses, medium effect sizes were observed for increased Openness (d = 0.79) and Positive Affect (d = 0.51) 48 hours after MDMA administration compared to placebo.

The forgotten psychedelic: Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin

Biorxiv· Oct 22, 2024· Mallaroni, P., Mason, N. L., Ramaekers, J. G. et al.

Using 7T resting-state fMRI in a double-blind, placebo-controlled crossover study, the authors show that acute 2C-B and psilocybin both reduce intra-network static connectivity while increasing between-network and subcortical–cortical coupling and brain complexity, but 2C-B causes less between-network desynchronisation and relative elevations in transmodal connectivity compared with psilocybin. These spatially divergent effects align with monoaminergic transporter and serotonergic receptor distributions and link transmodal-axis desynchronisation to behavioural measures, highlighting 2C-B as a distinct tool for psychedelic neuroscience and potential pharmacotherapies.

Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomized semi-naturalistic-lab feasibility study

Philosophical Transactions of the Royal Society B· Oct 21, 2024· Enriquez-Geppert, S,, Lietz, M. P., O'Higgins, F.

This randomised feasibility study (n=37) evaluates psilocybin-assisted (microdoses x 6) frontal-midline theta neurofeedback (NF) to improve executive functions (EFs) in participants with psychiatric disorders. Despite no significant improvements in tasks-based EFs, the experimental group reported medium to high gains in daily EFs, indicating the potential benefits of this neuromodulation technique for enhancing daily functioning.

The non-hallucinogenic serotonin 1B receptor is necessary for the antidepressant-like effects of psilocybin in mice

Biorxiv· Oct 21, 2024· Fleury, S., Nautiyal, K. M.

This preprint mouse study (n=29) finds that the serotonin 1B receptor (5-HT1BR) is necessary for psilocybin's antidepressant and anxiolytic effects, independent of its hallucinogenic properties. Using transgenic mice lacking 5-HT1BR and network analysis, the study demonstrates that this receptor influences brain-wide activity patterns and mediates acute and persistent behavioural responses to psilocybin, suggesting a novel mechanism for psilocybin's therapeutic effects.

Effects of classical psychedelics on implicit and explicit emotional empathy and cognitive empathy: a meta-analysis of MET task

Scientific Reports· Oct 18, 2024· Olami, A., Peled-Avron, L.

This meta-analysis (s=5, n=158) of classic psychedelic effects on empathy using the Multifaceted Empathy Test (MET) finds significant enhancement of explicit and implicit emotional empathy, with no effect on cognitive empathy. The analysis covers studies up to November 2023 examining LSD, psilocybin, and ayahuasca.

Acceptance as a possible link between past psychedelic experiences and psychological flexibility

Scientific Reports· Oct 16, 2024· Jylkkä, J., Krabbe, A., Sikka, P.

In a cross‑sectional survey of 629 people with classical psychedelic experience, psychological insight from a single experience — rather than frequency of past use — was associated with the psychological flexibility component Acceptance. Mediation analyses showed psychological flexibility mediated the relationship between past psychedelic use and current well‑being and ill‑being, suggesting that the quality of the experience, not use frequency, underpins lasting mental‑health benefits.

Human brain changes after first psilocybin use

Biorxiv· Oct 14, 2024· Carhart-Harris, R. L., Douglass, H., Erritzoe, D. et al.

In a placebo-controlled, within-subject neuroimaging study of 28 psychedelic‑naive participants, a single high (25 mg) dose of psilocybin produced lasting functional and anatomical brain changes from 1 hour to 1 month and improved cognitive flexibility, psychological insight and well‑being at one month. Diffusion MRI showed decreased axial diffusivity in prefrontal–subcortical tracts that correlated with reduced brain network modularity (which correlated with improved well‑being), acute increases in cortical signal entropy predicted one‑month well‑being via next‑day psychological insight, and none of these effects were seen with a 1 mg control dose.

Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer

Nature Mental Health· Oct 7, 2024· Agin-Liebes, G. I., Bogenschutz, M. P., Griffiths, R. R. et al.

This pooled analysis of two Phase II RCTs (n=79) evaluates psilocybin-assisted psychotherapy (PAP/PAT) for cancer-related distress. PAT significantly improves anxiety, depression, interpersonal sensitivity, hostility, obsession-compulsion, and somatization without inducing lasting phobia, paranoia, or psychosis.

Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome

npj Mental Health Research· Oct 6, 2024· Bostoen, T., Dadiomov, D., Dahan, A. et al.

This meta-analysis (2024, s=31) examines the correlation between subjective effects and therapeutic outcomes for ketamine (s=23, n=471) and psilocybin (s=8, n=183) in depression and substance use disorder (SUD) treatment. It finds modest mediating effects of subjective experiences on therapeutic outcomes, with psilocybin showing a stronger mediating effect (R² = 24%) compared to ketamine (R² = 5-10%), and a greater mediating effect observed in SUD compared to depression regardless of the substance used.

Perceived changes in mental health and social engagement attributed to a single psychedelic experience in autistic adults: results from an online survey

Psychopharmacology· Oct 5, 2024· Kamboj, S. K., Lee, J., Mandy, W. et al.

This online survey (n=233) of autistic participants with high autism quotient scores examines their experiences with psychedelic drugs and perceived changes attributed to their most 'impactful' psychedelic experience. It finds that the majority of participants reported reductions in psychological distress (82%) and social anxiety (78%), and increases in social engagement (70%), while 20% reported undesirable effects such as increased anxiety.

Psilocybin and 4-Bromo-2,5-Dimethoxyphenethylamine (2C-B) at Encoding Distort Episodic Familiarity

Biological Psychiatry· Oct 1, 2024· Doss, M. K., Mallaroni, P., Mason, N. L. et al.

This re-analysis of an RCT study (n=20) tested the acute effects of psilocybin and 2C-B on the encoding of emotional episodic memories. The study finds that both psychedelics impair estimates of recollection and familiarity, increase familiarity-based false alarms for emotional stimuli, and affect metamemory, indicating a common neurocognitive mechanism across these drugs.