Psychedelic Research Recap May 2024

This May, psychedelic research covers a wide range of topics, from therapy studies to real-world effects, new compounds, and broader impacts.

We start with a review that looks at the role of psychotherapy in psychedelic-assisted treatments. It points out the need for more research to understand how therapy works with psychedelics. Another report discusses guidelines for using touch in psilocybin group therapy, aiming for a safe and supportive environment. An interview study examines the existential distress some people feel after psychedelic experiences and how they cope.

Next, we look at real-world applications and challenges of psychedelic treatments. A study explores the factors that affect the use of esketamine nasal spray for treatment-resistant depression. Another article stresses the importance of monitoring new psychedelic medications to ensure they are safe and effective. A trial finds that feelings of awe may play a key role in ketamine’s antidepressant effects.

Innovation in psychedelics is highlighted by a study developing extended-release DMT patches for steady dosing. Another study uses new methods to show how DMT affects brain activity. We also examine the molecular workings of 5-MeO-DMT and compare it to other similar substances.

Several studies look at the broader effects of psychedelics. One finds that long-term ayahuasca users have good cognitive function and improved memory. Another study shows significant well-being improvements in older adults after guided psychedelic sessions. A study on psilocybin suggests it may enhance learning and exploratory behaviour. Lastly, research explores how psychedelics may reduce fear of death by changing beliefs.

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.

The Role of Therapy in Psychedelic Treatments

A recent review highlights the pressing need for more research into the psychotherapeutic components of psychedelic-assisted therapy (PAT). Despite the growing interest in PAT for various mental health conditions, the role of psychotherapy within this treatment is not well understood. The paper calls for a comprehensive approach to future research, emphasizing the integration of traditional psychotherapy techniques to optimize outcomes and develop federal guidelines. This review underscores the importance of understanding how psychotherapeutic support before, during, and after psychedelic sessions can enhance safety and efficacy.

A theory-building paper explores how psychedelic experiences can reduce fear of death. It suggests that these experiences promote non-physicalist metaphysical beliefs, supporting the “Relaxed Beliefs Under Psychedelics” (REBUS) model over other models. This shift in beliefs appears to play a crucial role in reducing death anxiety and has broader implications for how psychedelics might be used to address existential distress. The paper argues that these belief changes challenge the use of psychedelics in promoting a purely naturalistic spirituality.

An exploratory study investigates the relationship between changes in metaphysical beliefs and death anxiety following significant psychedelic experiences. The study finds that overall death anxiety decreases, with improvements linked to increased belief in panpsychism—the idea that consciousness is a fundamental attribute of all entities. This suggests that changes in specific metaphysical beliefs might be a key mechanism through which psychedelics alleviate fear of death.

A technical report outlines evolving guidelines for the use of touch in group psilocybin-assisted therapy sessions. These guidelines aim to create a safe, supportive environment while maintaining therapeutic boundaries. Initial guidelines were revised after unexpected experiences during early retreats, leading to more refined practices that include explicit consent, safe words, and body-based therapeutic techniques. The goal is to ensure that touch is used ethically and supportively, enhancing the therapeutic experience without causing harm.

Finally, a qualitative study dives into the existential distress some individuals face after psychedelic experiences. Participants reported persistent preoccupation with sense-making and confusion about existence and purpose. The study found that grounding practices, such as embodiment exercises and social normalization, managed distress.

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Novel Psychedelics and DMT Exploration

A study examined the use of AlphaFold2 (AF2; AF3 was recently released) models to predict the structures of receptors for ligand discovery. Researchers docked large libraries against AF2 models of σ2 and 5-HT2A receptors and compared the results with experimental structures. Remarkably, the hit rates and affinities were similar between AF2 models and experimental structures, despite differences in receptor conformations. This finding suggests that AF2 models, although not perfect, are valuable tools for discovering new ligands.

Another study focused on developing transdermal patches for extended-release DMT delivery. These patches were tested in Swiss Webster mice, showing that they provided consistent, extended drug release at non-hallucinogenic doses. The DMT patches achieved 77% bioavailability compared to intravenous administration, making them a promising option for outpatient treatment that avoids the intense hallucinogenic effects typically associated with DMT.

In an innovative approach to understanding the effects of DMT on the brain, researchers introduced the Harmonic Decomposition of Spacetime (HADES) framework. This method analyzed brain harmonic modes over time to see how DMT affects these patterns in healthy participants. The study found significant changes in low-frequency modes during DMT use, indicating that DMT alters the brain’s functional hierarchy, potentially explaining its profound effects on consciousness and cognition.

A molecular study investigated the therapeutic potential of 5-methoxytryptamines, particularly 5-MeO-DMT. Using cryogenic electron microscopy, receptor mutagenesis, and mouse behaviour studies, researchers mapped the pharmacology of 5-MeO-DMT and its interactions with the 5-HT1A receptor. The study identified a 5-HT1A-selective 5-MeO-DMT analogue that lacks hallucinogenic effects but retains anxiolytic and antidepressant properties. This discovery could lead to new treatments for neuropsychiatric disorders, highlighting the therapeutic promise of targeted psychedelics.

Real-World Studies on Psychedelic Medicine

As psychedelics gain acceptance in clinical settings, understanding their real-world application becomes crucial. Recent studies highlight the importance of surveillance and address barriers to treatment access.

A commentary stresses the need for innovative postmarket surveillance to maximize the real-world benefits of psychedelic-assisted psychotherapy. With promising results from late-phase clinical trials suggesting imminent FDA approval, the commentary warns that without proper surveillance, there could be misattributions of adverse events to illicit psychedelics. Effective surveillance programs should monitor access, safety, and effectiveness across various domains, but current data systems are inadequate. The authors call for intentionally designed surveillance mechanisms to ensure the safe and equitable use of these treatments.

A retrospective observational cohort study investigated factors influencing the use of esketamine nasal spray for treatment-resistant depression (TRD). The study included 966 esketamine initiators and 39,219 controls. Results showed that patients living closer to treatment centers were more likely to start and continue esketamine treatment. Factors such as posttraumatic stress disorder (PTSD), suicidal ideation (SI), and male sex increased the likelihood of initiation, whereas Medicaid coverage, substance use disorder, older age, and greater distance from treatment centers were associated with lower initiation rates. Barriers to continuous treatment included alcohol use disorder (AUD), travel distance, and minority community status, emphasizing the need for alternative care models to improve access to treatment.

Recent Human Studies on Psychedelics

An observational study explored the impact of long-term ayahuasca use on cognitive function among ritual users. The cross-sectional study included 48 participants: 16 experienced users, 16 beginners, and 16 non-users. Results showed no evidence of cognitive decline among ayahuasca users. Interestingly, experienced users had higher scores in tasks assessing verbal and visuospatial working memory compared to beginners, suggesting potential cognitive benefits from long-term use.

A prospective cohort study examined the effects of guided psychedelic sessions on well-being in older adults (OA) compared to younger adults (YA). The study involved 124 participants, split equally between OA and YA. Both groups showed significant improvements in well-being, especially among older adults with a history of psychiatric diagnoses. Although older adults experienced fewer intense subjective effects, the sense of community (Communitas) during the sessions played a significant role in their well-being improvements.

A double-blind, placebo-controlled study investigated psilocybin’s effects on emotional learning using a probabilistic cue-reward task. The study involved 30 participants and found that psilocybin preserved learning effects and suggested higher exploratory behavior compared to placebo. Notably, the 20 mg psilocybin group exhibited significantly better learning rates, highlighting psilocybin’s potential to enhance learning processes.

A cross-sectional study compared 400 Swedish psychedelic users with 400 non-users to explore mental health and personality traits. Psychedelic users reported lower depression levels and higher drug use rates. The study found that openness (a Big Five personality trait) was significantly higher among psychedelic users, contributing to their lower depression levels. These findings suggest that personality traits may influence the mental health outcomes of psychedelic users.

Finally, a randomized controlled trial investigated the psychological mechanisms behind ketamine’s antidepressant effects. The study involved 116 participants, with 77 receiving ketamine and 39 receiving a placebo. Participants who received ketamine reported heightened feelings of awe, which mediated improvements in depression scores at multiple time points post-infusion. This suggests that the experience of awe might play a key role in ketamine’s therapeutic effects.

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Last month, we added 16 studies to the database of over 2100 research publications.

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