Clinical Pharmacokinetics
March 28, 2017
Randall Brown, Christopher R. Nicholas, Nicholas V. Cozzi et al.
189 citations
Psilocybin, a naturally occurring hallucinogen, has shown promise as a therapeutic agent in pharmacology. In a study involving 100 participants, 70% reported significant mood improvements after psilocybin administration. The pharmacokinetics revealed that the active metabolite was detectable in urine for up to 24 hours post-ingestion. This highlights psilocybin's potential in medicine, emphasizing its unique chemical synthesis and alkaloid profile. As interest grows in psychedelics within drug studies and forensic toxicology, understanding these dynamics becomes increasingly vital for future applications.
Journal of Psychopharmacology
June 27, 2018
Christopher R. Nicholas, Kelsey M. Henriquez, Michele Gassman et al.
85 citations
Healthy participants given escalating doses of psilocybin (0.3, 0.45, and 0.6 mg/kg) showed a significant linear dose-related increase in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of complete mystical experiences. Dose 3 produced significantly higher transcendence of time and space scores than dose 1, while no dose-related differences emerged for total scores or mystical experience rate. Positive persisting effects 30 days after the last dose were significantly higher than negative ones, and a moderate increase in well-being or life satisfaction was associated with the maximum mystical experience score. Pharmacokinetic measures correlated with dose but not with mystical experience scores or rate, indicating that a complete mystical experience was not necessary for positive outcomes.
Drug and Alcohol Dependence
February 1, 2022
Christopher R. Nicholas, Julie B. Wang, A. Coker et al.
67 citations
MDMA-assisted therapy for severe PTSD may also reduce hazardous alcohol use without increasing illicit drug use. In a randomized trial, 90 adults with severe PTSD received either MDMA-assisted therapy or placebo plus therapy. Those in the MDMA group showed a greater reduction in alcohol use scores (average decrease of 1.02 points) compared to a slight increase in the placebo group (average increase of 0.40 points). Changes in drug use scores did not differ between groups. The findings suggest MDMA-assisted therapy could serve as an integrated treatment for co-occurring PTSD and alcohol or substance use disorders.
Psychological Medicine
November 4, 2020
Simon B. Goldberg, Benjamin Shechet, Christopher R. Nicholas et al.
66 citations
Classical psychedelics such as psilocybin, ayahuasca, and LSD produce significant psychological effects lasting at least 24 hours after administration, according to a systematic review and meta-analysis of 34 experimental studies involving 549 participants. Large effects were observed for reducing targeted symptoms in psychiatric samples, improving negative and positive affect, social outcomes, and existential or spiritual well-being, with between-group effect sizes ranging from Hedges' g = 0.84 to 1.08. Effects may be larger in clinical samples. Evidence for changes in personality traits or mindfulness was weak. No post-acute adverse effects were found, but high risk of bias, heterogeneity, and possible publication bias underscore the need for larger, placebo-controlled trials.
Frontiers in Psychiatry
March 14, 2023
Jonathan Brett, Elizabeth Knock, Paul Liknaitzky et al.
16 citations
Methamphetamine use disorder is a chronic condition with high relapse rates and limited effective treatments. Contingency management and psychotherapy show modest efficacy, while pharmacological options have little to no benefit. Psilocybin-assisted psychotherapy is emerging as a promising approach for substance use disorders, though no studies have yet examined it for methamphetamine use disorder. This review presents the rationale for using psilocybin-assisted psychotherapy to treat methamphetamine use disorder and describes practical considerations from early experience designing and implementing four clinical trials on this approach.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
Psychedelic Medicine
December 1, 2023
Julia Malicki, Amelia Baltes, Christopher R. Nicholas et al.
7 citations
A clinical trial found that giving psilocybin together with buprenorphine to people with opioid use disorder was safely tolerated and did not interfere with buprenorphine's effectiveness or psilocybin's subjective effects. The study faced feasibility challenges that required changes to the participant pool and eligibility rules, along with strategies to improve accessibility, reduce burden, and increase generalizability.
bioRxiv (Cold Spring Harbor Laboratory)
June 13, 2024
Christopher R. Nicholas, Matthew I. Banks, Richard Lennertz et al.
3 citations
preprint
Co-administering the amnestic benzodiazepine midazolam with psilocybin in 8 healthy participants partially impaired memory for the psychedelic experience while still allowing a conscious experience to occur. The degree of memory impairment was inversely associated with salience, insight, and well-being induced by psilocybin. These results suggest that memory of the acute psychedelic experience contributes to therapeutically relevant behavioral effects. Because midazolam blocks memory by blocking cortical neural plasticity, it may also help evaluate how the pro-neuroplastic properties of psychedelics contribute to their therapeutic activity.
International Journal of Mental Health and Addiction
March 17, 2026
Haley Maria Dourron, Melissa K. Bradley, Heith Copes et al.
Interviews with 19 people diagnosed with non-affective psychotic disorders who had used psychedelics revealed that, while some similarities exist in altered thinking and meaning attribution, most participants reported that psychedelic experiences did not closely resemble their psychosis. Sensory alterations, emotional experience, sense of control, and self-experience were points of contrast. When asked which drug most resembled their psychotic symptoms, the majority endorsed cannabis, followed by dissociative anesthetics and stimulants. The findings suggest that psychedelics may not accurately model many symptoms of psychosis and that interpreting psychedelic experiences as broadly psychosis-like may be misleading.
bioRxiv (Cold Spring Harbor Laboratory)
July 29, 2025
May Kung Sutherland, Christopher R. Nicholas, Richard Lennertz et al.
preprint
Psilocybin, a serotonergic psychedelic, induces neural plasticity and alters consciousness, while midazolam, a benzodiazepine, blunts plasticity and causes sedation and amnesia. In an open-label pilot study, 25 mg of oral psilocybin was given alongside intravenous midazolam at doses that allowed a full psychedelic experience but reduced memory of it. EEG recordings showed that 15-30 minutes after dosing, when midazolam was at its target concentration, beta power increased and the spectral exponent decreased. As psilocybin's effects emerged over the next six hours, Lempel-Ziv complexity and spectral exponent increased while broadband power decreased. These findings suggest psilocybin's effects persist even with midazolam, supporting its use in mechanistic studies.