A randomized crossover trial comparing the acute physiological and psychological effects of botanical formulations of oral psilocybin, oral psilocin, and sublingual psilocin.

In 30 seconds

This randomized, within-subject crossover trial compared acute effects and tolerability of botanical oral psilocybin, oral psilocin, and sublingual psilocin in 20 healthy adults. Participants completed up to four supported dosing sessions. Oral psilocin produced a temporal and subjective profile similar to oral psilocybin, with a lower burden of adverse effects. Sublingual psilocin was well tolerated at the doses tested, but apparently lower drug exposure limited comparison with oral administration. The study assessed acute physiological and subjective outcomes; it does not establish therapeutic efficacy for neuropsychiatric conditions.

Key findings

• Oral psilocin had a temporal and subjective profile similar to oral psilocybin, with fewer adverse effects.
• Sublingual psilocin was well tolerated at the dosages tested.
• Apparently lower drug exposure with sublingual dosing limited comparability with oral administration.

Why it matters

The findings suggest that the active compound psilocin can produce acute effects resembling oral psilocybin, while potentially differing in tolerability. They also highlight that delivery route may affect drug exposure, an important consideration when comparing formulations. These results inform further investigation of botanical preparations but do not show whether any formulation is effective or safe for treating a clinical condition.

What to keep in mind

The trial involved only 20 healthy adults and assessed acute effects. Lower apparent exposure with sublingual dosing limited comparison with oral administration.