Psychedelic Research Papers

This balanced-order crossover study (n=20) investigates the effects of LSD (75µg) on the pain neural network using fMRI in healthy subjects. The study finds that LSD modulates brain regions involved in pain processing, showing differences in activity and connectivity compared to placebo, and highlights potential implications for future cognitive science and pharmacology research.

This prospective longitudinal survey (n=8) focused on Canadians with Section 56 exemptions for legal psilocybin-assisted psychotherapy. Participants (Mage=52.3, all with cancer) showed significant improvements in anxiety, depression, pain, fear of COVID-19, quality of life, and spiritual well-being two weeks post-treatment. Most found the sessions meaningful but challenging, with one reporting decreased well-being.

This placebo-controlled study (n=53) investigates the effects of repeated low doses of LSD (15μg; 4x) on arousal, attention, and memory. LSD produces stimulatory effects, reducing EEG delta, theta, and alpha power, and enhancing pre-attentive processing, with the strongest effects in individuals with low baseline arousal. Inhibitory effects were observed in high-memory performers. The effects persisted during a 1-week follow-up, suggesting sustained neuroadaptations.

This in vitro study investigates the receptor binding profiles of NBOMe drugs compared to their 2C drug analogs and LSD. It finds that NBOMe drugs exhibit high affinity for 5-HT2A receptors, suggesting strong hallucinogenic effects similar to LSD, but with potentially more stimulant properties due to interactions with α1 receptors.

This in vitro study examines 2,5-dimethoxy-4-substituted phenethylamines (PEAs) including 2C-I, 2C-B, 2C-D, and 2C-H analogs, focusing on their receptor interactions. It finds these compounds act as 5-HT2A receptor antagonists, differing in potency based on specific substituents. This suggests their psychostimulant effects may not solely derive from 5-HT2A receptor agonism.

This within-subject MRI study (n=11) finds that inhaled DMT increases the mean population receptive field (pRF) sizes in the peripheral visual field of the primary visual cortex (V1). Documented by the Hallucinogen Rating Scale (HRS), this effect explains visual perceptual distortions like field blurring and tunnel vision, and supports the role of 5-HT2A receptor activation in controlling visual cortex activity.

This secondary analysis from a DMT study explores the impact of intentional cognitive interruptions on psychedelic experiences. The study investigates whether increasing cognitive load during the experience affects subjective ratings, hypothesizing that higher task demands would lower these ratings. Additionally, it examines whether reduced task demands correlate with larger reductions in long-term depressive symptoms.

This experimental study investigates the behavioral, neurochemical, and EEG profiles 2C-B in rats. 2C-B demonstrates biphasic effects on locomotion, initially inhibitory and then excitatory, contrasting with amphetamine which induces solely hyperlocomotion. Both compounds disrupt prepulse inhibition (PPI) of the startle reaction, albeit with different effects on acoustic startle response (ASR). In the nucleus accumbens (NAc), 2C-B increases dopamine levels but decreases 3,4-dihydroxyphenylacetic acid (DOPAC), suggesting potential psychotomimetic and addictive properties. EEG analyses reveal that low doses of 2C-B reduce power spectra and coherence, whereas high doses show biphasic effects on EEG power and coherence.

This comparative study on 2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines examines their activity as serotonin 5-HT2A/2C agonists. It finds that phenylisopropylamines generally exhibit higher efficacy than phenethylamines at the 5-HT2A receptor, but both act as partial agonists at the 5-HT2C receptor. The research highlights differential activation of phospholipase C (PLC) and phospholipase A2 (PLA2) pathways by these compounds in cell-based assays, with phenylisopropylamines showing stronger efficacy as head shake inducers in rats, supporting the concept of functional selectivity in receptor signaling pathways.

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.

This fMRI study explores the effects of psilocybin (a serotonergic psychedelic) and Salvinorin-A (a kappa-opioid receptor agonist) on resting-state functional connectivity (FC) in nonhuman primates. It reveals both drugs influence FC around the thalamus, claustrum, prefrontal cortex (PFC), and default mode network (DMN), with similarities and differences noted between them.

This scoping review (s=27) assesses the relationship between classic psychedelics and seizures. It finds that psychedelics may not increase seizure risk in healthy individuals or animals without other drugs, but concomitant use of substances like kambo or lithium could heighten the risk.

This study (n=26) empirically examines whether psychedelic experiences constitute transformative experiences. Results indicate that psychedelics can lead to significant changes in identity, values, beliefs, desires, and behavior, with 20 participants reporting unique insights and the majority experiencing behavioural changes. Participants felt informed and capable in their decision to use psychedelics, and many reported an enhanced ability to enact changes in their lives.

This qualitative study (n=11) explores practitioner perspectives on purging during Ayahuasca rituals at the Takiwasi Centre in Peru. Interviews with curanderos, plant preparers, and psychotherapists reveal three main explanatory models: spiritual-oriented, Amazonian-oriented, and clinical-oriented, all emphasizing the interconnectedness of purging and healing in Ayahuasca-assisted treatment for substance dependence.

This pre-print open-label study (n=8) co-administered psilocybin (25mg) with the amnestic benzodiazepine midazolam to assess the role of memory in the therapeutic effects of psilocybin. It finds that midazolam partially impaired memory while allowing a conscious psychedelic experience, with memory impairment inversely associated with salience, insight, and well-being induced by psilocybin, suggesting a role for memory in its therapeutic effects.

This in vitro and in silico study investigates whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. Compared with MDMA, these bioisosteres (ODMA, TDMA, and SeDMA) show similar activity at human serotonin, dopamine, and norepinephrine transporters but decreased agonist activity at 5-HT2A/2B/2C receptors and different hepatic metabolism, suggesting potential as safer therapeutic alternatives.

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.