Psychedelic Research Papers

This pooled analysis of nine double-blind, placebo-controlled, cross-over studies (n=213) investigates predictors of LSD effects in healthy subjects. It finds that LSD dose is the most influential predictor, with pre-drug mental states, personality traits, and previous hallucinogen experiences also significantly affecting the subjective experience.

This systematic review (2024) and meta-analysis (s=12) examines the therapeutic effects of single-dose and two-dose psilocybin administration on depressive symptom severity in MDD and TRD patients. It finds that psilocybin is highly effective in reducing depressive symptoms in both patient groups, with two-dose treatments potentially offering more pronounced and lasting effects (but no statistically significant difference).

This cell-based study investigates the role of serotonin receptors in the claustrum's response to psychedelic drugs. It finds that the claustrum is rich in 5-HT2C receptors on glutamatergic neurons and that serotonin and the psychedelic DOI have opposite effects on synaptic signalling, both mediated by 5-HT2C receptors rather than 5-HT2A receptors as previously thought.

This review (2024) examines the acute subjective effects of classic psychedelics, their relationship to risks and therapeutic benefits, and the current limitations in measuring these effects. It discusses existing measures, their construct validity, and predictive value for outcomes, while proposing recommendations for improving conceptualization and measurement in future research.

This systematic review (2024) and meta-analysis (s=214, n=3504) examines adverse events (AEs) associated with classic psychedelics in clinical or research settings. It finds that serious AEs were rare, occurring in approximately 4% of participants with preexisting neuropsychiatric disorders, while no serious AEs were reported in healthy participants.

This double-blind, randomized, placebo-controlled, crossover study (n=24) compares the acute effects of MDMA, S-MDMA, R-MDMA (the left and right-handed parts of MDMA), and placebo in healthy participants. It finds that S-MDMA (125 mg) induced stronger subjective effects and higher increases in blood pressure than R-MDMA and racemic MDMA while also increasing plasma prolactin, cortisol, and oxytocin more significantly. The study also notes differences in elimination half-lives and metabolite concentrations between the different forms of MDMA.

This pre-print, open-label study (n=10) investigates the effects of single-dose psilocybin (25mg) therapy in adults with severe alcohol use disorder (AUD). It finds significant reductions in alcohol consumption, craving, and increases in self-efficacy over 12 weeks following treatment despite notable between-participant pharmacokinetic variations.

This double-blind, randomized, placebo-controlled study (n=39) examines the effects of a single low dose of LSD (26µg) on event-related potentials during an emotional face oddball task. It finds that LSD significantly reduced the amplitude of N170 ERP to neutral faces and P300 ERP to neutral and happy faces, suggesting differential effects on brain responses to social and emotional information.

This review (2024) examines the potential role of the gut microbiome in mediating the effects of psychedelic drugs on behaviour. It argues that the current understanding of psychedelic mechanisms, focused primarily on serotonin 2A receptor agonism, is incomplete and needs to incorporate the gut microbiome and its (two-way) interactions with the brain.

This survey (n=68) of researchers and clinicians involved in MDMA-assisted therapy (MDMA-AT) examines opinions on clinical practices, training, and regulation. The study finds broad support for training standardization and highlights challenges in the national (European) approval process. Experts emphasize the importance of science-informed policy, active regulatory involvement, and international cooperation to integrate MDMA-AT into the European mental healthcare system, particularly for treating PTSD.

This theoretical review examines how psychedelics may lead to false insights and beliefs by connecting experimental work on false memories with insights under psychedelics using the active inference framework. It suggests that psychedelics increase the quantity and intensity of insights, which could include false beliefs, and proposes future research directions to minimize such risks while maximizing therapeutic potential.

This re-analysis (n=12) finds psilocybin-assisted group therapy associated with a significant decrease in HIV-related shame, with a median change of −5.5 points from baseline to 3-months follow-up. However, two participants experienced increased sexual abuse-related shame, raising important considerations for psilocybin therapy in trauma patients.

This cross-sectional survey (n=2000+) from the Canadian Psychedelic Survey explores the interplay between music and 11 classical and non-classical psychedelic substances in non-clinical settings. It finds most respondents report therapeutic benefits and enjoyment from music during psychedelic use, though benefits vary by substance. Only 10% and 22% support using unfamiliar music and music without understandable lyrics, respectively, suggesting current guidelines may need more nuanced, substance-specific research.

This online, retrospective survey (n=100) of individuals with a history of psychotic experiences and/or diagnoses explores the impact of memorable psychedelic experiences on their well-being and mental health. Most respondents (n=88) reported personal growth, mystical experiences, increased contemplation, improved insight, symptomatic improvements, and positive feelings, while 11% (n=11) described negative experiences such as symptom exacerbation, dysphoria, and terror.

This mouse model study examines the metabolic efficacy of the psychoactive aminoindane derivative MEAI on diet-induced obesity (DIO). MEAI treatment significantly reduced overweight and adiposity, improved glycemic control, decreased hepatic lipid accumulation, increased energy expenditure and fat utilization, and normalized voluntary locomotion without overstimulatory effects, suggesting its potential as a novel therapeutic approach for obesity and related metabolic disorders.

This commentary on MDMA and MDMA-like substances discusses the terms "empathogen" (prosocial and empathetic effects) and "entactogen" (introspective and self-awareness effects). It proposes "connectogen" as a unified term, highlighting MDMA's ability to create a sense of connection with oneself, others, the present moment, the body, the world, and spiritual principles.

This Phase I study evaluates the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of (2R,6R)-Hydroxynorketamine (RR-HNK) in healthy volunteers. It finds that RR-HNK has a minimal adverse event profile, no serious adverse events, and no anaesthetic or dissociative effects at all doses. The study also reports dose-proportional increases in PK parameters and promising PD outcomes, including gamma power increases in some participants and CNS exposure, supporting progression to Phase II.

This RCT follow-up study (n=39) investigates the long-term safety and efficacy of LSD-assisted therapy for anxiety (up to 94 weeks out). Participants reported a sustained reduction in anxiety (STAI-G; 33% remission) and depression (BDI; 49% remission) scores, decreased neuroticism, and increased extraversion, attributing positive long-term effects to the psychedelic experience.

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.