Psychedelic Research Papers

This reanalysis of a single-blind neuroscience study (n=17) explores the relationship between brain structure and function, focusing on subjective experience through the use of psychedelic substances. It uses connectome harmonic decomposition to demonstrate that the connectome harmonic repertoire and entropy increase under DMT, and these measures correlate with the intensity of subjective experience, similar to effects seen with psilocybin, LSD, and ketamine.

This double-blind, pilot study (n=28) investigates esketamine combined with mindfulness-based intervention (MBI) for individuals with alcohol misuse problems. Esketamine enhanced psychological engagement in MBI and transiently decreased alcohol cravings, while also resulting in greater mystical experiences and dissociative states compared to placebo.

This review evaluates the role of music in psychedelic-assisted therapies (PAT) and indigenous entheogenic ceremonies. It examines neuroscientific, psychological, and anthropological research, highlighting the need for personalized music protocols and the integration of traditional practices into modern treatment models to enhance clinical outcomes.

This consensus statement (n=27) identifies key ethics and policy issues for integrating psychedelic therapies into clinical practice. It reports 20 points of consensus across 5 ethical issues, with relevant actors responsible for implementation, and highlights areas needing further research and deliberation.

This secondary analysis of a randomized, double-blind, crossover trial (n=61) evaluates the impact of ketamine on sleep metrics in individuals with treatment-resistant depression (TRD) compared to healthy volunteers (HVs). It finds that while ketamine affects delta and alpha power during sleep, it does not significantly alter sleep macroarchitecture or mediate its antidepressant and anti-suicidal effects through sleep variables.

This survey (n=1,221) of psychedelic users assesses attitudes towards altered states of consciousness in psychedelic-assisted psychotherapy (PAP) and the potential of non-hallucinogenic analogues. Most participants (76%) believe altered states are crucial for therapeutic effects, but 61% would try a non-hallucinogenic alternative. Additionally, respondents consider $70–80 per hour a reasonable cost for PAP services, which is below current market rates.

This single-blind feasibility study (n=11) investigated the effects of one dose of ayahuasca (70ml/70kg) plus psychological support on the drinking patterns of college students with harmful alcohol consumption (mild alcoholism; AUD). A trend towards reduction in alcohol consumption (after statistical correction) was found.

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.

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.

This double-blind, placebo-controlled study (n=30) investigates the learning effects of psilocybin (up to 20 mg) in a probabilistic cue-reward task with emotional cues. It finds that psilocybin preserves learning effects, is non-inferior to placebo, and suggests higher exploratory behaviour. The 20 mg group showed significantly better learning rates than placebo.

This technical report (2024) describes the evolving guidelines for facilitator use of touch in a group retreat-based format of psilocybin-assisted therapy. The primary goal is to create a safe and supportive haptic experience during sessions, with a secondary goal of maintaining therapeutic boundaries and responding to participant experiences with empathy.

This prospective docking study compares the effectiveness of docking large libraries against unrefined AlphaFold2 (AF2) models of σ2 and 5-HT2A receptors with docking against experimental structures. It finds high and similar hit rates and affinities for both AF2 and experimental structures, despite conformational differences in orthosteric residues, and suggests that AF2 models, while differing from experimental structures, are still relevant and effective for structure-based ligand discovery.

This open-label pilot study (n=20) investigated the safety and efficacy of intranasal ketamine for treating a single cluster headache (CH) attack. While the primary endpoint of a 50% reduction in pain intensity within 15 minutes was not met, at 30 minutes post-treatment, pain intensity was significantly reduced by 59% on an 11-point scale, with no serious adverse events reported.

This randomized controlled trial (n=116) investigated the psychological mechanisms of ketamine's antidepressant effects. Participants receiving ketamine reported significantly heightened feelings of awe compared to those receiving a placebo. Awe experiences, as measured by the Awe Experience Scale (AWE-S), mediated depression outcomes (% improvement in MADRS scores) at multiple time points (24 hours and 5, 12, 21, and 30 days) post-infusion, indicating a potential role of awe in ketamine's therapeutic efficacy for depression.

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.

This theory-building paper (2024) examines how psychedelic experiences reduce fear of death by promoting non-physicalist metaphysical beliefs. It supports the "Relaxed Beliefs Under Psychedelics" (REBUS) model over other models of psychedelic therapy and argues that these belief changes undermine the use of psychedelics in naturalizing spirituality within the "neuroexistentialist" framework.

This qualitative study (n=26) explored existential distress following psychedelic experiences, finding persistent preoccupation with sense-making and confusion about existence and purpose. Participants reported cognitive, emotional, social, bodily, and functional impacts. They managed distress through embodiment practices and social/cognitive normalization.

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.

This pre-print brain imaging study (n=16, MEG) investigates the neural effects of psychedelics, focusing on hierarchy based on directed functional connectivity (FC). Administering LSD to healthy participants, researchers find LSD diminishes the asymmetry of directed connectivity over time and enhances machine learning classifiers' accuracy in distinguishing LSD from placebo based on hierarchy metrics. These findings suggest LSD weakens the brain's directed connectivity hierarchy by balancing neural signal senders and receivers.

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.

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.

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.

This pre-print prospective observational study (n=21) followed individuals with personality disorders (PDs) before, 2 weeks, and 4 weeks after psychedelic use. Another study (n=55) observed individuals with PDs before, 2-4 weeks, and 2-3 months after psychedelic use. Results indicate reductions in suicidal ideation (6.67%) and improvements in anxiety and depression symptoms, though some experienced increased anxiety and depression severity.

This theory building (2024) elucidates a new understanding of psychedelic modulation in the retinofugal pathway (between the eye and primary visual cortex). It suggests that disruptions in communication between cortical and subcortical regions, influenced by serotonin receptors, may lead to perceptual alterations and hallucinations.

This systematic review and meta-analysis (2024) examined the side effects of MDMA-assisted psychotherapy (MDMA-AP) across Phase II and III studies. Thirteen studies were included, with most showing an increase in side effects during medication sessions and the following week compared to control conditions. Despite these findings, the overall certainty of evidence was rated as very low to moderate, and the quality of side effects reporting was generally poor, suggesting further research is needed to fully understand the safety profile of MDMA-AP.

This conceptual synthesis proposes psychedelic-assisted therapy (PAT) as a potential treatment for functional seizures (FS), a subtype of functional neurological disorder (FND). Drawing on empirical evidence and complexity science, the argument is constructed for the potential efficacy of PAT in treating FS, highlighting FS as a cohort to investigate neural mechanisms of PAT. The synthesis also outlines a novel analytic roadmap to identify markers of FS diagnostic specificity and treatment success, aiming to bridge clinical neurology with psychedelic medicine and establish a new field of psychedelic neurology.

This comparative study (n=165) evaluated social cognitive functions and behaviors in chronic METH users, chronic MDMA users, and stimulant-naïve controls. METH users exhibited diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behavior regardless of provocation, and heightened trait anger. MDMA users showed a distinct rise in punitive behavior when provoked, with correlations suggesting associations between substance use patterns and social-cognitive deficits.

This EEG study (n=25) investigated the effects of MDMA (100mg) and methamphetamine (MA) on early visual processing of socio-emotional stimuli. MDMA enhanced the N170 component, sensitive to detecting faces, particularly for happy and angry expressions compared to neutral faces, while MA did not show similar effects.

This single-blind placebo-controlled study (n=40) investigated the neural and behavioral effects of acute ketamine in healthy participants. Results revealed robust inter-individual variability in both neural and behavioral responses to ketamine, with data-driven individual symptom variation mapping onto distinct neural gradients. These findings emphasize the need to consider individual variation in response to ketamine and suggest potential implications for developing precise pharmacological biomarkers in psychiatry.

This commentary (2024) provides an evidence-informed assessment of psychedelic research for treating depression. It discusses the shift in media reporting from overstating the risks to overly positive hype and emphasizes the need for clear science communication to set public expectations and inform policy decisions accurately.