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.
Clinical Pharmacology in Drug Development
April 6, 2020
Elyes Dahmane, Paul R. Hutson, Jogarao Gobburu
44 citations
Psilocybin, a compound being developed for major depressive disorder, is converted to psilocin after absorption. A single ascending dose study (0.3 to 0.6 mg/kg) found a significant but shallow relationship between psilocin concentration and QTc interval prolongation. At a clinical dose of 25 mg, the mean peak psilocin concentration is 18.7 ng/mL, associated with a mean QTcF change of 2.1 milliseconds (upper 90% confidence interval: 6.6 ms). The upper confidence limit crossed 10 ms at 31.1 ng/mL psilocin. Even at a supraclinical concentration of 60 ng/mL, the mean QTcF increase is 9.1 ms (upper limit 17.9 ms). Psilocin's short half-life (about 4 hours) suggests no accumulation with monthly oral dosing.
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.
JAMA Network Open
April 1, 2025
Paul R. Hutson
2 citations
No Summary
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.