Psychedelic Research Papers

AlphaFold2 structures guide prospective ligand discovery
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.
Science
May 2024
Cited by 0
Intranasal ketamine for acute cluster headache attacks—Results from a proof-of-concept open-label trial
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.
Headache
November 2021
Cited by 10
Experiences of Awe Mediate Ketamine's Antidepressant Effects: Findings From a Randomized Controlled Trial in Treatment-Resistant Depression
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.
Biological Psychiatry
May 2024
Cited by 0
Investigating the relationship between changes in metaphysical beliefs and death anxiety following a significant psychedelic experience
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.
Death Studies
May 2024
Cited by 0
How Do Psychedelics Reduce Fear of Death?
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.
Neuroethics
May 2024
Cited by 0
Navigating Groundlessness: An interview study on dealing with ontological shock and existential distress following psychedelic experiences
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.
SSRN
May 2024
Cited by 0
Barriers to Esketamine Nasal Spray Treatment Among Adults With Treatment-Resistant Depression
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.
Journal of Clinical Psychiatry
May 2024
Cited by 0
LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics
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.
Biorxiv
April 2024
Cited by 0
Structural pharmacology and therapeutic potential of 5-methoxytryptamines
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.
Nature
May 2024
Cited by 0
Psychedelic Experiences Increase Mind Perception but do not Change Atheist-Believer Status: A Prospective Longitudinal Study
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.
Journal of Psychoactive Drugs
June 2023
Cited by 1
Optimizing real-world benefit and risk of new psychedelic medications: the need for innovative postmarket surveillance
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.
Nature Mental Health
May 2024
Cited by 0
The Effect of Psychedelics on Individuals with a Personality Disorder: Results from two Prospective Cohort Studies
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.
Research Square
April 2024
Cited by 0
Visual hallucinations originating in the retinofugal pathway under clinical and psychedelic conditions
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.
European Neuropsychopharmacology
April 2024
Cited by 0
Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis
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.
Neuropsychopharmacology
April 2024
Cited by 0
Exploring psychedelic-assisted therapy in the treatment of functional seizures: A review of underlying mechanisms and associated brain networks
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.
Journal of Psychopharmacology
April 2024
Cited by 0
Chemical cousins with contrasting behavioural profiles: MDMA users and methamphetamine users differ in social-cognitive functions and aggression
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.
European Neuropsychopharmacology
April 2024
Cited by 0
The 3,4-methylenedioxymethamphetamine enhances early visual processing for salient socio-emotional stimuli
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.
European Journal of Neurology
April 2024
Cited by 0
Ketamine induces multiple individually distinct whole-brain functional connectivity signatures
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.
eLife
April 2024
Cited by 4
Mind the Psychedelic Hype: Characterizing the Risks and Benefits of Psychedelics for Depression
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.
Psychoactives
April 2024
Cited by 0
Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm
This pre-print open-label trial (n=117) administered intravenous ketamine in highly supportive environments to outpatients with elevated PTSD symptoms. The protocol included preparatory, integration, sensory immersion, and psychotherapy sessions, resulting in significant reductions in PTSD symptoms. The study highlights the potential of ketamine when delivered in a psychedelic therapy paradigm, suggesting it as a promising option for PTSD treatment resistant to other therapies.
Psyarxiv
April 2024
Cited by 0
Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial
This re-analysis of a single-blind, placebo-controlled study (n=19) of psilocybin (21mg/70kg) in combination with therapy (ACT, 8x) finds that psychological flexibility, mindfulness, and living according to one's values improved after psilocybin and stayed better through the 16-week study period. It also shows that greater psychological flexibility and experiential acceptance were linked with lower depression scores after psilocybin.
Scientific Reports
April 2024
Cited by 0
Methyl transfer in psilocybin biosynthesis
This structural study delves into the mechanism of PsiM, the enzyme responsible for the final step in psilocybin biosynthesis. The researchers present high-resolution crystal structures of PsiM, revealing insights into its methylation mechanism. They also propose that PsiM shares evolutionary origins with N6-methyladenosine writers, highlighting its potential for bioengineering to enhance psilocybin's therapeutic benefits.
Nature Communications
March 2024
Cited by 0
Trauma Under Psychedelics: MDMA Shows Protective Effects During the Peritraumatic Period
This retrospective cohort study (n=657) examines the acute experiences and peritraumatic processing of survivors from a high-casualty terror attack, with approximately two-thirds under the influence of psychoactive substances. Those who experienced the trauma under MDMA showed improved intermediate outcomes, including increased social support, more interactions, and better sleep quality, leading to reduced mental distress and PTSD symptom severity. These findings suggest a potential protective effect of MDMA during trauma.
Biorxiv
March 2024
Cited by 0
Getting in Touch with Touch: The Importance of Studying Touch in MDMA-Assisted Therapy and the Development of a New Self-Report Measure
This literature review examines the role of therapeutic touch in MDMA-assisted therapy (MDMA-AT), addressing concerns about power imbalances and ethical boundaries. It introduces the Touch Outcomes Measurement Inventory (TOMI) to assess client perceptions of touch in MDMA-AT, emphasizing the need for evidence-based and ethical guidelines in psychedelic-assisted therapy.
Psychedelic Medicine
March 2024
Cited by 0
Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants
This double-blind, placebo-controlled study (n=44) examines the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-MeO-DMT (up to 12mg), in healthy participants. BPL-003 was well tolerated, showing rapid absorption and elimination.
Journal of Psychopharmacology
April 2024
Cited by 0
A dual-receptor model of serotonergic psychedelics: therapeutic insights from simulated cortical dynamics
This pre-print, based on predictive processing and an energy-based model of cortical dynamics, explores the therapeutic mechanism of serotonergic psychedelics. It suggests that a combination of 5-HT2a and 5-HT1a agonism leads to a more psychologically tolerable acute experience and better therapeutic efficacy compared to pure agonists. This finding supports the clinical success of mixed serotonin agonists like LSD, psilocybin, and DMT, and suggests potential for the development of even more effective and tolerable psychotherapeutic agents, such as biased 5-HT1a agonist psychedelics like 5-MeO-DMT.
Biorxiv
April 2024
Cited by 0
Psychedelics and the 'inner healer': Myth or mechanism?
This re-analysis of an RCT (n=59) examines the concept of an 'inner healer' effect associated with psilocybin. Participants receiving a high dose of psilocybin (25mg, 2x) reported higher inner healer scores compared to those receiving a placebo (escitalopram). Furthermore, higher inner healer scores in the high-dose group correlated with improved depressive symptoms two weeks post-dosing, suggesting a potential therapeutic mechanism.
Journal of Psychopharmacology
April 2024
Cited by 0
The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action
This review (2024) examines the potential therapeutic mechanisms of action for alcoholism (AUD) treatment using 5-MeO-DMT. It highlights that 5-MeO-DMT can induce mystical experiences and ego-dissolution, leading to increased psychological flexibility and mindfulness, which may alleviate AUD symptoms. Additionally, preliminary evidence suggests that 5-MeO-DMT modulates neural oscillations and exhibits neuroplasticity and anti-inflammatory properties, indicating its potential clinical implications for AUD and related psychiatric comorbidities.
Addiction Biology
April 2024
Cited by 0
Naturalistic use of psychedelics does not modulate processing of self-related stimuli (but it might modulate attentional mechanisms): An event-related potentials study
This cross-sectional study (n=113) compared experienced psychedelic users (n=56) to nonusers (n=57) regarding neural responses to Self-name stimuli, known for activating self-representation. While no difference in P300 amplitude was found between users and nonusers for Self- or Target-names, users exhibited increased P300 amplitude for Other-names. Additionally, users showed a smaller increase in P300 amplitude for task-relevant stimuli compared to nonusers, suggesting potential alterations in attentional resource allocation rather than prolonged changes in self-representation due to psychedelic use.
Psychophysiology
April 2024
Cited by 1
Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial
This double-blind, placebo-controlled study (n=10) assesses the safety and efficacy of repeated pulse administration of psilocybin (10mg/70kg, 3x in 15 days) in cluster headache patients. Following the initial trial, eligible participants received a psilocybin pulse at least 6 months later and kept headache diaries for 8 weeks. Results indicate a significant reduction in cluster attack frequency following the psilocybin pulse, suggesting potential therapeutic benefits.
Journal of the Neurological Sciences
April 2024
Cited by 0

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Find all relevant psychedelic research papers in our ever-growing database. Here we cover and connect the latest research and seminal papers. From early open-label psychedelic studies with healthy volunteers to large-scale double-blind, placebo-controlled trials.

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