Psychedelic Research Papers

This review (2025) of the Swiss limited access scheme describes how approximately 100 physicians treated 723 patients with MDMA, LSD, or psilocybin in 2024, with patients typically receiving 2-4 psychedelic-assisted therapy sessions within 12 months for treatment-resistant conditions.

This analysis of an open-label observational study (n=30) found that magnesium-ibogaine therapy in combat veterans with traumatic brain injury (TBI) led to slower brain wave patterns and reduced neural complexity on EEG, which correlated with improvements in PTSD, anxiety, and cognitive function at one-month follow-up.

This meta-analysis of 17 trials (n=4,960) comparing control treatment outcomes across depression studies found that participants receiving control treatments in psilocybin trials showed significantly less improvement than those in SSRI or esketamine trials, with control response rates 14-23% lower, suggesting that psilocybin's reported antidepressant efficacy may be overestimated compared to conventional treatments despite having similar active treatment effects and lower dropout rates.

This double-blind, randomised controlled pilot study (n=30) found that psilocybin-assisted psychotherapy psilocybin (25mg; 2x; n=20) showed significantly higher abstinence rates at 12 weeks (55% vs 11%) compared to placebo (1mg; n=10) in patients with severe alcohol use disorder (AUD) and depression (MDD) who had recently completed detoxification.

This cross-sectional study (n=2,510) of US adults with psychedelic experience found that participants retrospectively reported widespread improvements in health behaviours including reduced alcohol (66%) and tobacco (49%) use, better dietary habits (49%), and decreased impulsivity (48-72%), with microdosers and frequent users showing greater positive changes.

This computational brain modelling study (n=42) compared how psilocybin (25mg; 2x) and escitalopram treatments affect brain hierarchy and neural plasticity in depressed patients. It found that psilocybin increased brain susceptibility to change while escitalopram reduced it, though both treatments promoted transitions towards healthier brain states.

This receptor profiling study (n=41 compounds) maps the pharmacological activity of classical psychedelics across 318 human G-protein-coupled receptors and, for LSD, over 450 human kinases. It finds that psychedelics act potently at nearly all serotonin, dopamine, and adrenergic receptors, with multiple 5-HT2A receptor signalling pathways linked to psychedelic effects in vivo.

This double-blind, randomised, placebo-controlled Phase I study (n=48) evaluates the safety, pharmacokinetics, and psychoactive effects of RE104 (psilocybin analog; Luvesilocin; a prodrug of 4-OH-DiPT) in healthy adults with prior psychedelic experience. RE104 was well tolerated up to 40 mg with no serious adverse events, and plasma levels of its active form correlated with subjective drug effect and mystical experience scores. The compound produced psilocybin-like effects with a shorter duration (3–4 hours), supporting further therapeutic investigation.

This Phase I clinical trial (n=36) of sublingual 5-MeO-DMT (6-12 mg weekly doses over four weeks) in adults with moderate to high anxiety/depression demonstrated good safety and tolerability with no significant adverse events, rapid absorption with peak plasma concentrations at 20 minutes, dose-dependent neurophysiological modulation without full psychedelic effects, and maintenance of normal cognitive and behavioral function.

This pharmacokinetic-pharmacodynamic analysis (n=46) of two Phase I trials of oral mescaline (100-800 mg) showed dose-proportional exposure with peak concentrations at 2 hours, a half-life of 3.5 hours, onset of effects around 1 hour post-dose, maximum effect intensity and duration ranging from 13% and 2.8 hours (100 mg) to 89% and 15 hours (800 mg), with 53% urinary excretion unchanged and 31% as the main metabolite, indicating at least 53% oral bioavailability.

This reanalysis of a single-blind, randomized study (n=16) using DMT (0-120mg) with harmine (0-180mg) in an ayahuasca-inspired (‘pharmahuasca’) formulation found that harmine significantly enhanced DMT bioavailability and prolonged absorption, resulting in higher sustained plasma concentrations and increased subjective psychedelic effects, with population pharmacokinetic/pharmacodynamic modeling revealing substantial interindividual variability in clearance, bioavailability, and sensitivity to psychedelic effects.

This longitudinal observational study (n=12,345) of U.S. residents found that naturalistic psychedelic use (n=505, 4.1% of participants) was associated with modest increases in depressive symptoms, particularly when occurring in 'risk contexts' characterised by negative mindset and lack of psychological support, with challenging psychedelic experiences mediating this relationship and suggesting that unsupervised psychedelic use may not be generally therapeutic and could worsen depression under certain circumstances.

This open-label pilot study (n=12) found that MDMA-assisted therapy (80-120mg; 2x) significantly reduced depression scores (MADRS) by 19.3 points and functional impairment (-11.7) in participants with moderate to severe major depressive disorder (MDD), with no serious adverse events reported over 8 weeks following treatment.

This double-blind study (n=23) using eye-tracking found that high doses of psilocybin mushrooms (0.5-3g dried) caused more localised visual exploration of paintings and less entropic fixation patterns compared to low doses, while increasing subjective emotional intensity without affecting aesthetic ratings of the artworks.

This pre-print, placebo-controlled, within-subjects neuroimaging study (n=28) of psychedelic-naive participants finds that a single high dose of psilocybin (25mg) produces anatomical and functional brain changes from one hour to one month post-dosing. These include decreased axial diffusivity in prefrontal-subcortical tracts, reduced brain network modularity (linked to improved well-being), and increased cortical signal entropy that predicts long-term psychological benefits. These effects were not observed with a 1 mg placebo dose.

This cross-species experimental study (n=21 humans; n=10 rats) finds that psilocin (18.2mg/70kg for humans; 0.3mg/kg for rats) impairs the ability to distinguish between static and moving images in both humans and rats. In humans, the impairment aligns with psilocin plasma levels and self-reported hallucination intensity. In rats, the effect is specific to motion perception, providing the first evidence of psilocin-induced visual distortions across species.

This Phase IV randomized controlled trial (n=378) found that esketamine nasal spray (Spravato) monotherapy at both 56mg and 84mg doses significantly reduced depression scores compared to placebo in treatment-resistant depression (TRD) patients at 28 days, with rapid onset of effect observed within 24 hours and moderate effect sizes of 0.48 and 0.63 respectively.

This preclinical mouse study (n=58) provides the first experimental evidence that psilocin extends cellular lifespan and that psilocybin promotes increased longevity in aged mice. The findings suggest psilocybin may have geroprotective potential, though the molecular mechanisms remain unclear.

This secondary analysis of treatment-resistant depression patients (n=31) with major depressive disorder or bipolar II disorder found that greater mystical experiences during the first 25mg psilocybin dose predicted better antidepressant outcomes, though this relationship was not observed for subsequent doses.

This observational retreat study (n=58) of military veterans attending psilocybin (n=13) or ayahuasca (n=45) retreats found significant improvements across all eight measured domains four weeks later, with the largest percentage reductions in depression (PHQ-9, 29%) and PTSD symptoms (PCL-5, 26%). Psilocybin outperformed ayahuasca on seven outcomes (ayahuasca led slightly on PTSD), men improved more than women on most scales, and greater baseline severity predicted larger post-retreat gains.

This open-label study (n=19) found that 10mg oral psilocybin produced a significant reduction in OCD symptoms compared to 1mg, with a large effect size (Cohen's d = 0.82) one week after dosing, particularly for compulsions rather than obsessions, though effects diminished over subsequent weeks.

This pre-print open-label trial (n=14) administered psilocybin (10-25mg) plus psychotherapy to people with bipolar II depression. It was well tolerated (only transient cardio spikes, mild anxiety/nausea/headache, and three temporary hypomania-or-suicidality events) and cut MADRS scores by 13–19 points at 21 days and 14 points at 90 days while boosting quality of life, with no excess mania or psychosis.

This systematic review (n=93 cases) found that psychedelic-induced psychosis, primarily caused by LSD and MDMA, lasted an average of 1.8 weeks and responded much better to second-generation antipsychotics (91% response rate) than first-generation antipsychotics (27% response rate), though one-third of patients later developed schizophrenia spectrum disorders.

This pre-print simultaneous PET-MRI study (first of its kind) demonstrates that LSD increases global cerebral blood flow and internal carotid artery flow without affecting artery diameter (opposite to psilocybin's effects), while decreasing global connectivity (particularly in visual networks) and increasing network entropy and spatial complexity, with researchers also observing an anticlockwise hysteresis loop (dynamic lag between an input and an output) between plasma levels and subjective effects that challenges existing hypotheses about psychedelic mechanisms of action.

This mixed-methods analysis (n=973 across multiple cohorts) examines how psychedelic experiences influence “meaning in life” using the Meaning in Life Questionnaire (MLQ) across three contexts: a psilocybin clinical trial for depression, a single-arm healthy volunteer study, and a naturalistic retreat-based study. It finds strong increases in the “presence of meaning” subscale and modest decreases in “search for meaning,” with enhancements linked to improvements in mental health and to the intensity of mystical, ego-dissolution, and emotional breakthrough experiences.

This double-blind, placebo-controlled, cross-over study (n=40) found that two doses of psilocybin (18.2mg/70kg) administered at least 56 days apart (avg. 15 months) produced positive lasting effects in healthy individuals regardless of previous psychedelic experience, sex, or setting, with challenging experiences in controlled environments not causing adverse outcomes, supporting psilocybin's psychological safety for repeated use.

This data analysis of three studies (n=84) validates a three-item Peak Experience Scale (PES) for rapidly assessing 5-MeO-DMT experiences, demonstrating that the scale shows strong internal consistency (Cronbach's α=0.896), correlates highly with established psychedelic experience measures (MEQ-30, EDI, 5D-ASC), and could effectively guide dosing regimens for rapid-acting psychedelics.

This secondary analysis of a randomised, double-blind, placebo-controlled trial (n=31) demonstrated that an ayahuasca-inspired DMT/harmine formulation significantly enhanced mindfulness and compassion (both self-compassion and compassion for others) one day post-treatment, with more pronounced effects in high-sensitivity participants.

This analysis of fMRI data (n=15) examined how LSD (75μg) affects local brain activity and connectivity, finding that LSD decreased both measures in somatosensory/visual areas, with additional activity decreases in Default Mode and Fronto-Parietal networks and connectivity decreases in subcortical regions, with these changes occurring primarily in brain regions with high densities of D2 and 5HT1a receptors, suggesting complex neurobiological mechanisms underlying LSD's effects.

This pre-print reports an observational pilot study (n=12) examining salivary oxytocin ('love/bonding hormone') dynamics during LSD-assisted psychotherapy (100-150μg) for treatment-resistant depression (TRD), finding significant time-dependent variations in both oxytocin levels and subjective drug intensity ratings, suggesting oxytocin may serve as a potential biomarker for psychedelic therapy.