Optimal dosing for psilocybin pharmacotherapy: Considering weight-adjusted and fixed dosing approaches

This analysis of psilocybin dosages given in 10 previous studies (n=288) found no effect of weight, nor gender, on the effects (acute or long-term) of the dosage (20-30mg) of psilocybin used. The authors recommend a fixed dosing approach going forward to simplify dosing regimes.


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 30mg/70 kg (inclusive). Separate multivariate regression analyses examined the relationships between demographic variables including body weight and subjective effects in participants receiving 20mg/70kg (n=120), participants receiving 30mg/70kg (n=182), and participants whose weight-adjusted dose was about 25mg (to approximate the fixed dose that is currently being evaluated in registration trials for major depressive disorder) (n=103).

Results: In the 20mg/70kg and 30mg/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 113kg) 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.”

Authors: Albert Garcia-Romeu, Frederic S. Barrett, Theresa M. Carbonaro, Matthew W. Johnson & Roland R. Griffiths


The first author, Albert Garcia-Romeu, already spoke about these findings/recommendations all the way back in 2017.

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