Psilocybin is a psychedelic tryptamine being studied for depression and substance use disorders. In an open-label study of 12 healthy adults, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg were given at monthly intervals. No psilocybin was found in plasma or urine; its active metabolite psilocin had an elimination half-life of 3 hours (standard deviation 1.1). Renal clearance of intact psilocin accounted for less than 2% of total clearance, indicating no dose reduction is needed for mild-moderate renal impairment. Body weight did not predict variation in psilocin clearance. No serious adverse events occurred. A fixed 25 mg dose approximates the exposure of a 0.3 mg/kg dose.
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.