In brief
- Twenty healthy volunteers took oral psilocybin, oral psilocin, and sublingual psilocin in random order, all derived from whole-mushroom extracts.
- Oral psilocin, at 17.5 mg, produced a trajectory and intensity very similar to 25 mg of psilocybin, but with fewer adverse effects.
- This is a small trial without a placebo arm involving healthy individuals; it compares formulations rather than measuring therapeutic efficacy.
A team at the University of California, San Francisco, has put three different ways of consuming the active ingredient in mushrooms head-to-head. The results, published August 29 in the Journal of Psychopharmacology, suggest that administering psilocin directly avoids discomfort without diminishing the experience. It is the kind of technical detail that rarely makes headlines, yet it will shape the future of psilocybin.
A potentially unnecessary metabolic detour
Technically, psilocybin does not alter anyone’s perception. It is an inactive molecule that the body transforms by removing a phosphate group to convert it into psilocin, which is what binds to the brain’s serotonin receptors. Recent research detailed how this molecule acts within the brain. Almost all clinical trials over the last decade have used synthetic oral psilocybin, so this preliminary step is taken for granted. The question asked in San Francisco was simple: what happens if you deliver already-formed psilocin? You can read about how this family of compounds works in our psilocybin and magic mushrooms guide.
How the trial was conducted
Twenty healthy adults participated—ten men and ten women—with an average age of 40.1 and a range of 25 to 50. The design was a randomized, triple-blind crossover study: neither the participant, the researcher, nor the person scoring the results knew what was being administered in each session. Each person attended up to four times. The doses were 25 mg of oral psilocybin, 17.5 mg of oral psilocin, and 2.18, 4.36, or 8 mg of sublingual psilocin. None of the three were synthetic; they were prepared from whole-mushroom botanical extracts, specifically the PEX10, PEX20, and PEX30 formulations from the Canadian company Filament Health. All sessions included support and psychotherapy before and after. Vital signs and subjective scores of intensity and psychedelic experience were recorded. The trial, led by Joshua Woolley, began in May 2022 and is listed in the U.S. public registry under code NCT05317689.
It is worth noting who pays and who signs: Filament Health provided the formulations and is listed as a collaborator on the trial; two of its executives appear among the authors of the paper. This does not invalidate the data, but it is context the reader deserves to have.
What they found
Oral psilocin produced a temporal curve and subjective profile very similar to oral psilocybin. The difference lay in the toll: the authors describe a lower burden of adverse effects with psilocin. The sublingual route was also well-tolerated, but the exposure achieved was apparently lower, which prevents a direct comparison with the oral route. The conclusion they reach is cautious: oral psilocin could offer tolerability advantages, and more studies are needed to refine both the botanical formulations and the routes of administration.
What it implies
It is best not to overstate the findings. Twenty healthy people with prior psychedelic experience are not a sample from which to deduce antidepressant effects, and the study did not include a placebo because it sought to compare formulations rather than measure clinical efficacy. That said, the data has potential. If a preparation produces the same effect with fewer side effects, the session becomes more manageable, which matters as much in an authorized service as in any context where someone decides to use mushrooms on their own. The fact that the comparison was made with whole-mushroom extracts, rather than laboratory molecules, adds another interesting nuance to a field that had spent years considering that discussion settled. For those looking for practical guidelines, our harm reduction guide explains how dose, route, and context influence the experience.
Source
- Tai ML, Szigeti B, Downey AE et al. A randomized crossover trial comparing the acute physiological and psychological effects of botanical formulations of oral psilocybin, oral psilocin, and sublingual psilocin. Journal of Psychopharmacology, August 29, 2026. DOI 10.1177/02698811261478603.
- Comparison of the Effects of PEX20 (Oral Psilocin), PEX30 (Sublingual Psilocin), and PEX10 (Oral Psilocybin) in Healthy Adults, NCT05317689. ClinicalTrials.gov, trial registry.
- University of California, San Francisco. Comparing the Effects of Psilocin and Psilocybin in Healthy Adults. UCSF Clinical Trials, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
