Psychedelic Research Papers

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

This double-blind, randomized study (n=27) assessed the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in TRD patients as add-on therapy. Patients received either 160 mg/day or 240 mg/day KET01 or placebo for 14 days, with the primary endpoint being the change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. Results suggest a positive trend towards antidepressant efficacy with 240 mg/day KET01.

This prospective cohort study (n=124, 62 older adults) investigates the effects of a guided psychedelic group session on well-being in older adults (OA) compared to younger adults (YA). Mixed linear regression analyses show significant improvements in well-being in both groups, particularly amplified in OA with a history of psychiatric diagnosis. Acute subjective psychedelic effects were attenuated in OA compared to YA, but a psychosocial measure of Communitas emerged as a predictor in OA, indicating the potential value of relational components in psychedelic group settings for OA.

This placebo-controlled study (n=36) investigated fMRI data from experienced meditators undergoing focused attention and open monitoring meditation before and after a five-day psilocybin-assisted (22mg/70kg on day 4) meditation retreat. Psilocybin-induced positive derealization, coupled with enhanced open-monitoring meditation, correlated with the optimal transport distance between open monitoring and resting state. This suggests that enhanced meta-awareness through meditation combined with psilocybin may mediate insightfulness, offering potential novel brain markers for positive synergistic effects between mindfulness practices and psychedelics.

This meta-analysis (n=1100; s=14) of clinical trials on patients with depression (MDD) receiving ketamine or esketamine reveals a substantial placebo response, accounting for up to 72% of the overall treatment response. The study emphasizes the importance of considering the placebo response in clinical practice to maximize the benefit to patients.

This pre-print single-blind study (n=14) used multimodal neuroimaging techniques (fMRI + EKG) to investigate brain activity and autonomic physiology during DMT (20mg) altered state of consciousness. Results reveal unique brain activity substates, with increased superior temporal lobe activity and hippocampal deactivation under DMT, correlating with auditory distortions and meaningfulness of the experience, respectively. Moreover, increased heart rate under DMT correlates with hippocampal and medial parietal deactivation, suggesting a potential link between sympathetic regulation and positive mental health outcomes following psychedelic administration.

This reanalysis of a trial (n=59) investigates the mechanisms underlying the efficacy of Psilocybin Therapy (PAT) versus Escitalopram Treatment in patients with depression (MDD) over a 6-week trial period. Acute psychological experiences such as "mystical experience" and "ego dissolution" were found to mediate the effect of treatment condition on depressive response, suggesting a mechanistic role of these experiences in the treatment of depression via PAT.

This cell & mice study explores the psychopharmacological profile of amino-substituted 5-MeO-tryptamines, focusing on their interactions with serotonin receptors and transporters, as well as their psychoactive and thermoregulatory properties. The study demonstrates selectivity for 5-HT1AR over 5-HT2AR among examined compounds using radioligand binding methodologies and computational docking analyses, and 5-MeO-pyr-T was identified as the most potent partial 5-HT releaser.

This observational study (n=16.255) investigates the association between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents, utilizing a genetically informative design. Results suggest that psychedelic use may be associated with reduced psychotic symptoms after adjusting for other drug use, while associations with manic symptoms seem to be linked to genetic vulnerability to schizophrenia or bipolar I disorder.

This randomized, waiting list-controlled clinical trial (n=24) for depression (MDD) assessed the therapeutic alliance between participants and intervention facilitators in psilocybin-assisted therapy (PAT). Therapeutic alliance significantly increased from the final preparation session to one-week post-intervention, with a stronger alliance predicting depression scores at various post-intervention time points. Stronger alliances were correlated with peak ratings of mystical experiences and psychological insight, which in turn were correlated with depression scores.

This pooled analysis (n=85; doses=113) of three randomized crossover studies evaluates the safety pharmacology of psilocybin (15-30mg). Psilocybin induced stronger effects at higher doses, with 25 mg and 30 mg doses showing increased anxiety. However, overall, psilocybin was found to be safe in terms of acute psychological and physical harm, with no serious adverse reactions reported, suggesting its potential safety for controlled research settings.

This pre-print (n=13) investigates the subjective experiences of individuals engaging in psilocybin microdosing in their daily lives. Combining momentary ecological assessments and retrospective interviews, participants reported varied effects, including loosening of mental structures, increased salience of external stimuli, flexible cognition, and ego-dystonic contents.