Psychedelic Research Papers

This randomized double-blind, active placebo-controlled trial (n=24) investigates the analgesic efficacy of esketamine on fibromyalgia pain. The study found short-term pain reduction in the ketamine group but no significant differences in treatment effects on pain scores during the 2.5-hour or the 8-week follow-up, suggesting that a short-term infusion of ketamine is insufficient for long-term analgesic effects in fibromyalgia patients.

This case presentation (n=1) describes a subject with red-green colour vision deficiency (mild deuteranomaly) who experienced a partial improvement in their condition after using 5g of dried psilocybin mushrooms. Self-reported Ishihara Test data showed the improvement peaking at 8 days and lasting at least 16 days post-administration, although further observations were confounded by other substance use.

This single-blind, placebo-controlled, crossover study (n=6) assessed the psychological effects and tolerability of ayahuasca (35, 52.5, 75mg DMT/70kg) in healthy male volunteers with prior experience. The study found dose-dependent increases in various psychological effects, with the tea being well-tolerated from a cardiovascular perspective, though modified physical sensations and nausea were the most frequently reported somatic-dysphoric effects. Ayahuasca induced changes in perceptual, affective, cognitive, and somatic spheres, with stimulatory and visual psychoactive effects of longer duration and milder intensity than intravenously administered DMT.

This re-analysis of the psilocybin (25mg) versus escitalopram (antidepressant, 6 weeks) RCT finds that in the psilocybin arm, experiential avoidance reductions led to improvements in mental health outcomes (e.g. depression severity). Note: the trial itself was insignificant on the primary measure of depression.

This systematized review (s=82) examines the current evidence for best therapeutic practices during administration sessions with serotonergic psychedelics and entactogens (e.g. MDMA) as adjuncts to psychotherapy. The study finds that the effects of different therapeutic models, methods, techniques, and more complex interventions on therapeutic outcomes have not been investigated rigorously, with most available evidence being anecdotal.

This real-world (n=269) analysis of esketamine (Spravato) use finds nearly 50% of patients had their first pharmacy claim approved. Of those approved, 45% had eight or more treatment sessions (as recommended), though spread over 85 days (versus 28 per the label). Patients had lower health utilization, but this could be due to factors outside of the esketamine treatment (e.g. regression to the mean).

This triple-masked, randomized, placebo-controlled trial (n=40) of adults with major depressive disorder (MDD) found no short-term effect on depression severity (measured by MADRS) after a single dose of intravenous ketamine (35mg/70kg) compared to placebo (saline) during anaesthesia for routine surgery.

This systematic review (s=10 trials) evaluates the quality of adverse event (AE) reporting in published clinical trials studying esketamine for resistant depression. It reveals that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles compared to ClinicalTrials.gov, with the majority being psychiatric and cardiovascular events and 94% concerning patients from esketamine groups.

This pre-print brain-mapping study in mice (2023) shows that repeated ketamine administration decreases dopamine neurons in the midbrain and increases in the hypothalamus. It also reveals further evidence for the plasticity-increasing effects of ketamine.

This survey (n=2045) of Canadian psychedelic users finds psilocybin, MDMA and LSD are the most commonly used. It also reports positive (82%) life changes and challenging experiences (52%). Motivations for use include fun, self-exploration, general mental well-being, and personal growth.

This pre-print analysis of online (Reddit) posts finds that classical psychedelics benefited 75% of those who mentioned the effects (10% negative). The benefits spanned behavioural change (e.g. reduced stuttering), emotional benefit, and cognitive changes.

This re-analysis from a randomized control trial (n=33) investigates the effects of IV ketamine or midazolam (active control) on military veterans with late-in-life treatment-resistant depression using two EEG neural complexity markers (Lempel-Ziv complexity and multiscale entropy). The study found that both complexity markers increased 30 minutes post-infusion, with time-varying effects on system-wide contributions to the evoked glutamatergic surge. Still, no relationship was observed between complexity and reduction in depressive symptoms.

This pre-print open-label trial (n=14) organised by ATMA Journey Centers finds psilocybin to be safe, with peak systolic (146) and diastolic (94) blood pressures to be within acceptable ranges. Secondary analyses find a significant decrease in depression (QIDS-SR16) and high mysticism scores (MEQ-30).

This online survey (n=1221) examines people's information-seeking behaviour using psychedelics naturally, revealing that most participants rely on their own experimentation and experiences, Internet websites, friends, discussion forums, books, and scientific journals. The study also found that articles in scientific journals, psychedelic nonprofits, and university researchers were the most trusted sources, while government agencies and pharmaceutical companies were the least trusted.

This survey study (n=214k; NSDUH) finds lowered odds on three out of four social impairment measures in those who use MDMA (lifetime use; correlational). Only mescaline also showed a relationship with reduced odds of difficulty dealing with strangers (one of the measures), but other (classical) psychedelics studied showed no relationship with the social impairment measures.

This double-blind, randomized Phase III trial (n=227) finds no significant difference between esketamine plus a new antidepressant versus only the antidepressant (and a placebo) at day 28 on depression scores (MADRS). The study reports one death in the esketamine group. It also states esketamine to be "effective and safe" though only the first claim could be credibly made if one only looks at the immediate (24-hour) effects.

This whole-brain simulation reproduces earlier studies where increased entropy was found under the influence of psychedelics. The changes weren't uniform, with larger effects in the optical area. The changes were not well-explained by looking at where the most serotonin (2a) receptors were but mapped closely to the topological (spatial) properties of how the brain is connected.

This pre-print re-analysis (n=48) of microdosing LSD (5-20μg) finds that LSD reduces the influence of our expectations (precision-weighted local priors) on what we think time should feel like (under-reproduction bias). When controlling for the expectations, the bias disappears, indicating that LSD microdosing reduces the relative weighting of priors (expectations).

This open-label study (n=66) finds that four ketamine infusions (35mg/70kg) led to improvements in cognition both immediately (measured after the first and fourth infusion) and up to five weeks later. As seen in other studies, antidepressant effects reverted to baseline at five weeks.

This survey (n=918) of self-reported substance abusers finds that the majority support research into MDMA-assisted therapy (68%). Six out of ten would be willing to try it if appropriate for their situation.

In this within-subject, placebo-controlled, pre-print study (n=11), participants received four doses of DMT (6-18 mg bolus + infusion over 30 minutes). Subjective effects were kept stable over the infusion, while plasma DMT concentrations increased (indicating acute psychological tolerance). Findings indicate that extended DMT infusion is safe and effective in healthy subjects.

This survey (n=32) and interview (n=15) study of those who had negative psychological responses to psychedelics (>72 hours) identified potential causal factors, such as unsafe or complex environments during or surrounding the experience, prior psychological vulnerabilities, high or unknown drug quantities, and young age. However, due to the small sample size and selective recruitment approach, the study can't be used to infer the prevalence of adverse outcomes from psychedelic use.

This double-blind cross-over brain imaging study (n=22) of psilocybin combined EEG with transcranial magnetic stimulation (TMS) to reveal that psilocybin produces a chaotic pattern of brain activity (versus placebo; LZc complexity under eyes closed). Using TMS, the authors could measure the Perturbational Complexity Index (PCI) due to the stimulation. The difference between psilocybin and placebo on PCI wasn't significant.

This fMRI analysis study (n=74 total) looks at how three different drugs - nitrous oxide, ketamine, and lysergic acid diethylamide (LSD) - affect the way different parts of the brain communicate with each other. By comparing brain scans taken before and during drug use, the study found that all three drugs reduced connectivity within certain networks in the brain, while enhancing connections between different networks. These effects were seen in areas of the brain that are important for our conscious experiences.

This review (2023) discusses the limitations and biases in using psychometric assessments to measure "mystical" experiences in psychedelic research. The authors argue that the existing operationalizations of mystical experiences fail to acknowledge their Christian bias and suggest more culturally-sensitive approaches. They also propose complementary "non-mystical" approaches to understanding similar phenomena for more robust theoretical and empirical approaches.

This meta-analysis (s=14) of ketamine's anti-anxiety (anxiolytic) effects finds immediate (within 12 hours) effects lasting up to two weeks.

This retrospective analysis (n=100) of the effectiveness of ketamine (35mg/70kg) for borderline personality disorder (BPD) in those with treatment-resistant depression (TRD) finds that intravenous ketamine significantly reduces symptoms of depression, borderline personality, suicidality, and anxiety in patients with comorbid BPD and TRD. Both BPD-positive and BPD-negative groups showed significant improvements in the primary outcome measures, with no significant difference between groups.

This placebo-controlled, randomized, naturalistic study (n=80) of repeated microdoses of LSD (10μg, 14x, 6w) finds improved ratings, on dosing days, on creativity, connectedness, energy, and other wellness ratings. Though these transient changes were found, no enduring changes to mood and cognition were observed.

This paper explores integrating Tibetan Buddhist contemplative tradition with psychedelic-assisted therapy (PAT), highlighting the absence of contemplative traditions in current psychedelic therapy discourse. By comparing phenomenological similarities between Tibetan Buddhist meditation and psychedelic experiences, the paper suggests that incorporating the Tibetan framework of view, meditation, and action may enhance the efficacy of PAT.

This open-label study (n=12) of patients suffering from Body dysmorphic disorder (BDD), an obsessive preoccupation with misperceptions of appearance, finds that psilocybin (25mg) plus psychological support (6 sessions) resulted in a response (>30% decrease in BDD-YBOCS) in 58% of participants. Secondary measures such as negative affect, disability, and conviction of belief also significantly decreased.