Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches. (April 2021)

• Record Type: Journal Article
• Authors: Garcia-Romeu, Albert; Barrett, Frederick S; Carbonaro, Theresa M; Johnson, Matthew W; Griffiths, Roland R
• Other Names: Rucker James J guest-editor.; Seth Pallab guest-editor.
• Is Part Of: Journal of psychopharmacology. Volume 35:Number 4(2021)
• Page Start: 353
• Page End: 361
• Publication Date: 2021-04
• Subjects: Hallucinogen -- psilocybin -- psychedelic -- weight-adjusted dosing -- fixed dosing -- serotonin -- mystical experience; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881121991822
• Languages: English
• ISSNs: 0269-8811

Abstract

Background: Growing evidence suggests psilocybin, a naturally occurring psychedelic, is a safe and promising pharmacotherapy for treatment of mood and substance use disorders when administered as part of a structured intervention. In most trials to date, psilocybin dose has been administered on a weight-adjusted basis rather than the more convenient procedure of administering a fixed dose. Aims: The present post hoc analyses sought to determine whether the subjective effects of psilocybin are affected by body weight when psilocybin is administered on a weight-adjusted basis and when psilocybin is administered as a fixed dose. Methods: We analyzed acute subjective drug effects (mystical, challenging, and intensity) associated with therapeutic outcomes from ten previous studies (total N = 288) in which psilocybin was administered in the range 20 to 30 mg/70 kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20 mg/70 kg ( n = 120), participants receiving 30 mg/70 kg ( n = 182), and participants whose weight-adjusted dose was about 25 mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) ( n = 103). Results: In the 20 mg/70 kg and 30 mg/70 kg weight-adjusted groups, and in the fixed dose group, no significant associations were found between subjective effects and demographic variables including body weight or sex. Across a wide range of body weights (49 to 113 kg) the present results showed no evidence that body weight affected subjective effects of psilocybin. Conclusions: These results suggest that the convenience and lower cost of administering psilocybin as a fixed dose outweigh any potential advantage of weight-adjusted dosing.