Same Psilocybin and LSD Doses Showed Stronger Effects in Women
A team at Maastricht University went back through two of its own placebo-controlled trials and split the results by sex. The drugs were psilocybin at 15 mg, LSD at 50 micrograms and 2C-B at 20 mg. Every participant got the same amount. Women reported stronger effects than men on all three. The blood levels say it was not because they absorbed more.
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| Key Takeaway | Detail |
|---|---|
| The analysis | Two double-blind placebo-controlled trials pooled, 94 drug sessions from 43 male and 51 female participants |
| The drugs | Psilocybin 15 mg, 2C-B 20 mg and LSD 50 micrograms |
| The finding | Significant sex differences on five measures after adjusting for age |
| The strongest | Feeling under the drug’s influence, reduced vigilance, and impaired control and cognition |
| The ruling out | No sex difference in peak blood concentration, so exposure was equivalent |
| The status | A preprint, not yet peer reviewed, and a secondary analysis |
What the Maastricht Team Pooled
Psychedelic trials report wide variation between individuals. Sex has rarely been examined as a reason.
The team combined two of its own randomized, double-blind, placebo-controlled studies in healthy volunteers. That gave 94 drug sessions, 43 from male participants and 51 from female participants.
Three compounds were involved. Psilocybin at 15 mg, 2C-B at 20 mg and LSD at 50 micrograms. 2C-B is a synthetic psychedelic studied far less often than the other two.
These are active doses, not microdoses. The question was what the experience felt like, not whether it sharpened anything.
Linear mixed models tested for sex differences, with treatment and sex as factors and age as a covariate. Both source trials are registered in the Dutch trial register, and the authors declared no competing interests.
Where the Difference Showed Up
Female participants rated most measures higher than male participants. On most of them the gap was numerical rather than statistical.
After adjusting for age, five measures reached significance. The most robust three were feeling under the drug’s influence, reduced vigilance, and impaired control and cognition.
Effect sizes there were medium to large, which is not a trivial gap.
The pattern held across all three compounds rather than appearing with one of them.
Empathy was measured too, using the Multifaceted Empathy Test. No sex difference appeared on any empathy measure. Ratings came from visual analogue scales during the session, plus two standard altered-states questionnaires afterward.
It Was Not a Dose Difference
The obvious explanation is body size. A fixed dose lands harder on a smaller person.
The team measured it. Peak blood concentrations showed no sex difference.
So the stronger ratings came at equivalent drug exposure.
The authors read that as pharmacodynamic rather than pharmacokinetic. The difference is in the response, not the amount circulating. That is the part worth noticing, because dosing by weight would not address it.
What a Pooled Reanalysis Can and Cannot Do
Neither original trial was designed to test sex differences. This analysis looked for them afterward.
That design finds hypotheses well and confirms them poorly. Pooling two trials also means pooling their differences, in setting, staff and screening.
Ninety-four sessions is a small base for a question this broad.
The paper is a preprint. It has not been through peer review.
The authors are explicit that the findings are preliminary and call for adequately powered trials.
The Evidence Base Has Been Mostly Male
This lands on a gap we have written about before. A systematic review we covered in September found the microdosing literature was roughly 70 percent male. We laid that out in our look at what the controlled microdosing trials actually found.
A field that studies mostly men will not notice a difference that shows up in women.
So the useful reading here is not that women respond more. It is that nobody had checked carefully.
What It Would Change in a Clinic
The authors name three implications. Dosing, informed consent and safety monitoring.
Consent is the most immediate. A patient told what to expect should be told what the range looks like.
Monitoring is the second. Reduced vigilance and impaired control are the measures that moved most.
Those are the measures that decide how long somebody stays and who takes them home.
None of this is actionable for an approved product yet. Psilocybin and LSD remain Schedule I, a status we covered when a federal report told states to prepare for approval.
A Variable Worth Measuring on Purpose
An oral LSD tablet has already cleared three Phase 3 trials. Approval decisions will follow data like that, not like this.
What this preprint argues is narrower. Sex belongs among the variables those trials record and report.
That is a cheap thing to add to a protocol and an expensive thing to discover afterward.
Patients looking for supervised care can start with our directory of verified ketamine clinics.
This article is for informational purposes and is not medical advice. Psilocybin, LSD and 2C-B are Schedule I substances under federal law and are not approved treatments.
