Objectives: This scoping review aimed to synthesize the existing data about psilocybin pharmacokinetics to learn what has been described regarding body disposition and safety when psilocybin was used in controlled research settings.

Methods: We performed a scoping literature review following the framework proposed by the JBI manual for evidence synthesis. Controlled clinical trials reporting pharmacokinetic data of psilocybin were considered appropriate for inclusion. We extracted the data on psilocybin pharmacokinetics and summarized it from the available literature on this topic. We also performed an exploratory-descriptive analysis using study level data to examine the relationship between dose of psilocybin and maximum serum concentrations (Cmax).

Results: We initially identified 850 articles, of which 5 were included. These trials included 112 healthy volunteers who received psilocybin in a controlled clinical setting. The peak concentration of psilocin in plasma (Cmax) ranged from 8.2 ng/mL to 37.2 ng/mL (median = 17, IQR = 11.9 to 23.5). The maximal concentrations (Cmax) of psilocin were reached (Tmax) around 2 hours, ranging from 1.7 hours to 2.2 hours (median = 2, IQR = 1.9 to 2.1) after psilocybin oral administration. Elimination half-life was between 1.2 hours and 3.3 hours (median = 2.0, IQR = 1.6 to 2.8). A strong positive relationship between dose and Cmax ( R2 = 0.95) was found. No serious adverse events were observed. We did not find studies reporting pharmacokinetic data from patients with depression or cancer patients transitioning to palliative care.

Conclusions: In summary, this review unveils oral psilocybin pharmacokinetics in healthy adults, revealing gaps in its application to target populations like those with depression or in palliative care.