Psychedelic Research Recap May 2024
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.
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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.
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 commentarystresses 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.
Papers Published in May 2024
19 studies from the Blossom database published this month.
Attitudes of psychedelic users regarding cost of treatment and non-hallucinogenic alternatives
In a survey of 1,221 naturalistic psychedelic users, 76% judged altered states of consciousness to be very or extremely important for therapeutic effects, yet 61% said they would be willing to try a non-hallucinogenic analogue. Respondents considered about $70–80 per hour a reasonable fee for preparation, dosing and integration—substantially below current market projections for psychedelic-assisted psychotherapy.
Coming back together: A qualitative survey study of coping and support strategies used by people to cope with extended difficulties after the use of psychedelic drugs
This international qualitative study of 608 people who experienced extended difficulties after psychedelic use identified a range of individual (notably meditation, prayer, reading and journaling) and social (friends/family, therapists/coaches) coping strategies reported as helpful, with valued social features including feeling heard, non‑judgemental attitudes and shared experience. The findings offer practical guidance for developing therapeutic interventions and educational resources to support those with post‑psychedelic difficulties.
Psychedelic-assisted psychotherapy: Where is the psychotherapy research?
This review (2024) scrutinizes the role of psychotherapy in psychedelic-assisted psychotherapy (PAP/PAT) for mental health conditions. It underscores a significant research gap in understanding the psychotherapeutic elements within PAT, despite its assumed importance for safety and efficacy. The paper calls for a transdisciplinary approach in future research to optimize PAT clinical outcomes and inform federal guidelines.
Long-term ayahuasca use is associated with preserved global cognitive function and improved memory: a cross-sectional study with ritual users
This observational, cross-sectional study (n=48) investigates the influence of ritualistic ayahuasca consumption on cognition among experienced (n=16) and beginner (n=16) ayahuasca users and a control group (n=16). It finds no evidence of cognitive decline among ayahuasca users, with experienced users showing higher scores in tasks assessing working verbal and visuospatial memories compared to beginners.
Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT)
This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioural and pharmacokinetic studies performed with lead patch formulation (F5) in male and female Swiss Webster mice showed that transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose, with a 77% bioavailability compared to IV at two dosages.
Harmonic decomposition of spacetime (HADES) framework characterises the spacetime hierarchy of the DMT brain state
This article (2024) introduces the Harmonic Decomposition of Spacetime (HADES) framework to analyse brain harmonic modes over time. Using this, the effects of DMT on these modes in healthy participants were examined. HADES showed significant changes in low-frequency modes during DMT use, indicating alterations in the brain's functional hierarchy under psychedelics.
How Do Psychedelics Reduce Fear of Death?
The paper argues that psychedelic experiences reduce fear of death primarily by inducing non‑physicalist metaphysical belief change rather than by purely psychological or physiological mechanisms. This finding supports the REBUS model of psychedelic therapy and challenges "neuroexistentialist" aims to naturalise spirituality, since the benefits seem to depend on persuading people away from a broadly naturalistic worldview.
Investigating the relationship between changes in metaphysical beliefs and death anxiety following a significant psychedelic experience
This exploratory study (n=155) investigates the relationship between changes in metaphysical beliefs and death anxiety following a significant psychedelic experience. It finds a significant overall reduction in death anxiety, with improvements correlated positively with increased belief in panpsychism, while no other metaphysical beliefs showed a correlation.
Structural pharmacology and therapeutic potential of 5-methoxytryptamines
This molecular study investigates the underpinnings of 5-MeO-DMT pharmacology and its therapeutic potential through cryogenic electron microscopy structures of 5-HT1A, medicinal chemistry, receptor mutagenesis, and mouse behaviour. The research characterizes molecular determinants of 5-HT1A signalling potency, efficacy, and selectivity, contrasting the structural interactions and pharmacology of 5-MeO-DMT with LSD and clinically used 5-HT1A agonists.
Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study
This prospective longitudinal survey (n=657) finds that people who use psychedelics recreationally increase in prescribing 'mind perception' to living and non-living targets (e.g. plants and animals). However, unlike previous studies, they didn't find changes in metaphysical beliefs along the Atheist-Believer scale.
Barriers to Esketamine Nasal Spray Treatment Among Adults With Treatment-Resistant Depression
This retrospective observational cohort study (n=966 esketamine initiators, n=39,219 controls) examines factors influencing esketamine initiation and continuation for treatment-resistant depression (TRD). Initiators resided closer to treatment centres, with initiation rates decreasing significantly with distance. Factors associated with increased initiation included posttraumatic stress disorder, suicidal ideation, and male sex, while Medicaid, substance use disorder, older age, and greater distance were associated with lower initiation rates.
Optimizing real-world benefit and risk of new psychedelic medications: the need for innovative postmarket surveillance
This commentary (2024) highlights the promising results from late-phase clinical trials on psychedelic-assisted psychotherapy, suggesting imminent FDA approval and wider adoption in the USA. However, it emphasizes the crucial need for postmarket surveillance to ensure real-world benefits are maximized, and potential risks are mitigated. Without proper surveillance, there's a risk of incorrect conclusions, such as attributing adverse events to illicit psychedelics. Effective surveillance programs should monitor access, safety, and effectiveness across various domains, but current data systems are inadequate, necessitating intentionally designed surveillance mechanisms.
Personality traits explain the relationship between psychedelic use and less depression in a comparative study
In a national Swedish sample of 400 psychedelic users and 400 matched non‑users, psychedelic users reported lower depressive symptoms, much higher openness and greater drug use; the apparent link between psychedelic use and reduced depression was statistically explained by lower neuroticism, indicating personality traits partly mediate this association.
Comparing neural correlates of consciousness: from psychedelics to hypnosis and meditation
This comparative neuroimaging study (n=107) compares the neural correlates of two pharmacological methods, psilocybin (n=23) and LSD (n=25), and two non-pharmacological methods, hypnosis (n=30) and meditation (n=29), in inducing altered states of consciousness (ASC). The results reveal distinct connectivity patterns associated with pharmacological and non-pharmacological interventions, predictability at an individual level, and unique behavioural-neural relationships between psilocybin and LSD, all contributing to a broader understanding of the mechanisms of ASC and their potential therapeutic applications in psychiatric disorders.
Effect of Repeated Intravenous Esketamine on Adolescents With Major Depressive Disorder and Suicidal Ideation: A Randomized Active-Placebo-Controlled Trial
This placebo-controlled trial (n=54) investigates the efficacy and safety of esketamine (iv, 17.5mg, 3x) in adolescents suffering from depression (MDD) and suicidal ideation (SI). It shows significant reductions in Columbia Suicide Severity Rating Scale (C-SSRS) Ideation and Intensity scores and Montgomery-Åsberg Depression Rating Scale (MADRS) scores in the esketamine group compared to the midazolam (placebo) group at day six, with maintained antisuicidal and antidepressant responses at four weeks post-treatment.
Effective-connectivity of thalamocortical interactions following d-amphetamine, LSD, and MDMA administration
This re-analysis of a double-blind, placebo-controlled, crossover study (n=25) investigated the effects of LSD, MDMA and dextroamphetamine on brain measures (thalamocortical and corticothalamic interactions in resting-state fMRI data). Compared to placebo, all three substances increased the effective-connectivity from the thalamus to specific unimodal cortices while reducing their influence on the thalamus, revealing increased bottom-up and decreased top-down information flow; LSD uniquely increased effective-connectivity to both unimodal and transmodal cortices.
Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation - Clinical and safety results
This double-blind, randomised study (n=27) assessed the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in TRD patients as add-on therapy. Patients received either 160 mg/day or 240 mg/day KET01 or placebo for 14 days, with the primary endpoint being the change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. Results suggest a positive trend towards antidepressant efficacy with 240 mg/day KET01.
Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial
This double-blind, placebo-controlled study (n=10) assesses the safety and efficacy of repeated pulse administration of psilocybin (10mg/70kg, 3x in 15 days) in cluster headache patients. Following the initial trial, eligible participants received a psilocybin pulse at least 6 months later and kept headache diaries for 8 weeks. Results indicate a significant reduction in cluster attack frequency following the psilocybin pulse, suggesting potential therapeutic benefits.
Psychedelics and the neurobiology of meaningfulness
This commentary (2023) explores the neurobiological mechanisms underlying the experience of meaningfulness induced by psychedelics, focusing on 5-HT2A receptor activation. It proposes multiple hypotheses: 1) 5-HT2A activation increases the salience of environmental stimuli, 2) psychedelics may reactivate salient autobiographical memories, and 3) psychedelics may create novel neural representations that generate prediction errors.