Safety pharmacology of acute psilocybin administration in healthy participants

Psilocybin is being studied for its therapeutic potential in various mental health disorders, such as depression, anxiety, and addiction. Initial studies suggested that psilocybin is generally safe when used under controlled conditions, but more research is needed to better understand its safety profile. We report safety pharmacology data from a pooled analysis of three randomized crossover studies that included 85 healthy participants and 113 single-dose administrations of psilocybin. Single oral doses included 15 mg, 20 mg, 25 mg, and 30 mg psilocybin dihydrate. We investigated subjective effects, blood pressure, heart rate, body temperature, acute and subacute adverse effects, reports of flashbacks, and liver and kidney function before and after the studies. The 20, 25, and 30 mg doses of psilocybin produced stronger effects than the 15 mg dose. Psilocybin at all doses induced higher “good drug effects” than “bad drug effects.” Only the 25 and 30 mg doses increased anxiety. Psilocybin elevated autonomic effects only moderately. Tachycardia (>100 beats/min) was observed with 7% of all psilocybin administrations. Body temperature >38° was reached in 7%, 9%, 17%, and 32% of the participants with the 15, 20, 25, and 30 mg doses, respectively. Kidney and liver function parameters were unaltered at the end of the study. Five participants (6%) reported transient flashback phenomena. No serious adverse reactions occurred. These findings suggest that a single administration of psilocybin is safe with regard to acute psychological and physical harm in healthy participants in a controlled research setting.