Sex Differences in Acute Responses to Psychedelics: Evidence for Greater Subjective Intensity and Impairment in Female Participants
Natasha L. Mason, Eline Chm Haijen-bongers, Kim P. C. Kuypers, Aline Frick, Stefan W. Toennes, Pablo Mallaroni, Johannes G. Ramaekers
bioRxiv (Cold Spring Harbor Laboratory) July 13, 2026 Peer reviewed DOI: 10.64898/2026.07.08.737179 via OpenAlex
Summary
Female participants reported more intense subjective effects from psilocybin, 2C-B, and LSD than male participants, including feeling more strongly under the drug's influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects consistent across the three drugs. No sex differences were found in empathy measures or peak drug concentrations in blood. These findings suggest pharmacodynamic mechanisms—how the body responds to the drug—rather than pharmacokinetic differences in drug exposure explain the sex differences. The results have implications for dosing, informed consent, and safety monitoring in psychedelic research.
Study at a glance
| Design | pooled analysis of two double-blind, placebo-controlled studies |
|---|---|
| Sample size | 72 |
| Population | healthy volunteers |
| Key finding | Female participants experienced more intense acute subjective effects and greater perceived impairment under psychedelics than male participants, independent of age and not explained by drug exposure. |
Abstract
Serotonergic psychedelics are advancing as psychiatric treatments, yet acute responses vary between individuals and the contribution of sex, a fundamental biological variable, remains largely unexamined. We pooled two double-blind, placebo-controlled studies in healthy volunteers (N = 72; 31 male, 41 female) comparing psilocybin 15 mg, 2C-B 20 mg, and LSD 50 μg. Linear mixed models tested sex differences in acute subjective effects (visual analogue scales), retrospective altered-states ratings (5D-8209; and 11-ASC), empathy (Multifaceted Empathy Test), and peak plasma blood concentrations (Cmax, AUC), with treatment, sex, their interaction, as fixed factors, and age as a covariate. Female participants reported numerically higher subjective ratings than male participants on most measures. After adjustment for age, sex differences remained significant for feeling under the drug's influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects. These effects were largely consistent across the three drugs. No sex differences emerged on any empathy measure or in peak drug concentrations. Female participants may experience more intense acute subjective effects and greater perceived impairment under psychedelics, independent of age and not explained by drug exposure. These preliminary findings, implicating pharmacodynamic rather than pharmacokinetic mechanisms, have implications for dosing, informed consent, and safety monitoring, and underscore the need to treat sex as a biological variable in adequately powered psychedelic trials.