Psychedelic Research Recap February 2024

What happens if psychedelics become a regular part of therapy?

In a way, that is what the majority of research on psychedelics is trying to answer. Studies analysing the safety, to mapping out the effectiveness in various domains, including those featured here in February, help us understand psychedelics as medicines. But, a new study looking back at the therapeutic use of psychedelics in Switzerland put all of this in a new light, building on over 3000 sessions, it showcases how (in a limited setting) psychedelics can be used responsibly.

Other studies this month look at sexual functioning after psychedelics (better than after SSRIs), dive deeper into exploring expectancy effects, and we get a closer look at the effects of microdosing LSD in a controlled trial.

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.

Controlled Trials Investigating AUD, Sexual Functioning & A Qualitative Follow-Up

A pilot fMRI study examined how psilocybin affected neural reactivity to alcohol and emotional cues in patients with alcohol use disorder. Participants received either psilocybin or placebo prior to the fMRI scans. Psilocybin increased activity in areas like the prefrontal cortex and caudate while decreasing activity in regions like the insula and cerebellum. These neural changes suggest psilocybin may enhance goal-directed behaviour, improve emotion regulation, and reduce craving.

A mixed-methods study combined data from a naturalistic survey (see more surveys later in the recap) and a controlled trial to investigate psychedelics’ effects on sexual functioning. In the survey, psychedelic use was associated with improved sexual pleasure, communication, partner satisfaction, and body image. The clinical trial found patients treated with psilocybin for depression reported positive sexual changes, unlike those treated with an SSRI antidepressant. Despite different populations, these converging results indicate psychedelics may have beneficial effects on sexual functioning.

Two separate studies looked at the impact of intravenous DMT on mental health in healthy volunteers. A placebo-controlled trial and prospective study showed significant reductions in depression scores 1 to 2 weeks after DMT administration. Reductions in trait neuroticism were only seen in the placebo-controlled group. Changes in depression and anxiety correlated with the intensity of peak experiences during the DMT session, suggesting these states may facilitate therapeutic effects.

In a randomized controlled trial, researchers used EEG to assess the impacts of repeated low-dose LSD (10µg) on neural plasticity. Traditional event-related potential analysis didn’t show changes in visually-induced plasticity. However, computational modelling revealed alterations in laminar connectivity within the visual cortex after LSD microdosing, indicating enhanced neural plasticity not captured by standard peak analysis methods.

A qualitative study explored the perspectives of treatment-resistant depression (TRD) patients participating in a psilocybin clinical trial (the COMPASS Phase II trial). Three major themes emerged: challenges with building trust and managing expectations; navigating the profound psilocybin experience; and a need for more comprehensive treatment like additional psilocybin sessions and integrated psychotherapy. Patient insights highlighted strategies to optimize protocols.

Open-Label Studies, Opening New Doors

One fascinating recent study used machine learning to examine how baseline resting-state functional connectivity (FC) measured with fMRI could predict symptom improvement from psilocybin-assisted therapy for treatment-resistant depression (TRD). The results showed that connectivity in visual, default mode, executive, and salience networks could predict early symptom changes as well as longer-term responsiveness up to 24 weeks after treatment with a high degree of accuracy.

Moving to a different psychedelic, an open-label longitudinal study looked at the impact of ayahuasca use on aesthetic experiences. Participants reported increases in aesthetic experiences at both one-week and one-month follow-ups after attending an ayahuasca retreat, despite no correlation between acute subjective effects during the retreat and these longer-term changes.

Another study on the same subjects found significant increases in gratitude, nature relatedness, and nature appreciation at one week and one month after an ayahuasca retreat experience, compared to baseline. Ratings of mystical experiences and awe during the ayahuasca sessions correlated with these increases, suggesting their potential role. However, the quality of experiences was more important than quantity in influencing post-ayahuasca changes.

A different area receiving research attention is the legal medical use of classical psychedelics like LSD, MDMA, and psilocybin for psychotherapy in certain jurisdictions like Switzerland. A recent commentary provided insights into over 1000 case permits issued there since 2014, allowing an estimated 2000-3000 individual psychedelic-assisted therapy sessions so far. The authors discuss practical considerations like application procedures, treatment frameworks, ethical standards, and the need for ongoing therapist training as this modality continues developing.

Lastly, an open-label randomized waitlist-controlled trial evaluated the feasibility, safety, and preliminary efficacy of psilocybin-assisted psychotherapy specifically for treatment-resistant depression (TRD) in a complex clinical population. Participants received flexibly repeated doses of psilocybin along with psychotherapy, showing greater depression reduction compared to the waitlist period. Interestingly, repeated psilocybin doses were associated with further symptom improvements over time.

Surveying Psychonauts to Measure Outcome (Causes)

A prospective survey study explored the impact of psychedelic microdosing on emotional regulation, empathy, and ADHD symptoms in adults with severe ADHD, compared to those using conventional medications. Initial results showed benefits for microdosing in areas like cognitive reappraisal, expressive suppression, perspective-taking, and personal distress. However, when compared to a control group using standard ADHD meds after four weeks, only the improvement in expressive suppression persisted, while enhancements in cognitive reappraisal and empathy disappeared. The microdosing group did show reduced overall ADHD symptoms compared to the conventional medication group.

Analyzing self-reports from 766 individuals, mostly from Western countries, another study identified distinct consumer groups based on their MDMA consumption settings (party, private home, mixed) and intentions (euphoria/energy, self-insight, mixed). Those in the self-insight and mixed intentions clusters reported considerably more long-term socio-emotional benefits from MDMA use compared to those solely seeking euphoria and energy. No significant differences were observed between the setting clusters.

Through quantitative analysis of 240 online psychedelic trip reports, a third survey-like study tested two competing theories on the mechanisms behind psychedelics’ therapeutic potential: metaphysical belief theory and predictive self-binding theory. Path analysis supported the predictive self-binding model, showing psychological insight, rather than metaphysical beliefs, uniquely predicted beneficial outcomes. The positive effects of ego dissolution and therapeutic intent were fully mediated by psychological insight. These findings counter the notion that psychedelic benefits stem from adopting supernatural beliefs after mystical experiences.

Reviews Examining Psychedelic Interactions and Novel Compounds

A review by Balázs Szigeti and Boris Heifets explores the impact of participant expectations on psychedelic clinical trials, highlighting the challenge of maintaining effective blinding as doses increase and the potential bias introduced by positive expectancy. Covering both micro- and macrodose trials, the review suggests that understanding and managing expectancy could enhance trial rigour and treatment outcomes in future psychedelic research.

Turning our attention from the head towards the heart, another review outlines the effects of various hallucinogenic drugs, including psilocybin, LSD, DMT, and others, on cardiac function in humans. While primarily stimulating serotonin receptors like 5-HT2A to produce hallucinogenic effects in the brain, these substances can also impact the heart, potentially increasing contractility and heart rate, which could predispose individuals to arrhythmias.

Next to reviewing the literature, another group of researchers also conducted a meta-analysis synthesizing data from 10 contemporary studies (n=304) to evaluate the lasting effects of serotonergic psychedelics on cognition, creativity, emotional processing, and personality. Overall, no statistically significant effects were observed for most outcomes. However, a meta-analysis revealed faster reaction times in the psychedelic groups for recognizing disgust and sadness emotions.

How we got these insights is partly the work of neuroimaging techniques like fMRI, PET, and MEG/EEG in modern psychedelic research, providing insights into both the acute and longer-term therapeutic effects of these substances. Evidence from neuroimaging informs computational models, offering a comprehensive understanding of psychedelics’ effects on human consciousness and supporting the advancement of psychedelic therapies.

The Other Psychedelic Studies from February 2024

Next to these trials, open-label studies, surveys, and reviews there were a handful of other psychedelic studies of note that were published last month. Here is a quick mini recap of each one:

• A preclinical study showed methylone had rapid antidepressant and anxiolytic effects by affecting neuroplasticity gene expression in brain areas linked to PTSD and depression. Unlike MDMA, methylone showed no off-target receptor activity, suggesting potential for treating PTSD with higher specificity.
• A hypothesis paper proposes psychedelics like LSD and psilocybin induce altered states by activating the 5-HT2A receptor system, leading to a state of “synthetic surprise.” This disrupts expectations and sensory input based on predictive coding, with implications for using psychedelics to induce surprise and promote change therapeutically.
• A pre-print EEG study explored differences in brain activity between psychedelic users and non-users during self-related thought processing. One dataset suggested weaker alpha/beta power increases in users, especially in self-processing brain regions, but a second dataset did not replicate these effects, possibly due to sample size/resolution limits.

What you can find on Blossom

Last month, we added 21 studies to the database of over 2000 research publications.

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