Psilocybin Efficacy With or Without Pimavanserin Pretreatment

Summary

Twenty healthy adults (≥21 years old) will be enrolled to evaluate the efficacy of a single oral dose of psilocybin (25 mg) administered with or without pretreatment using oral pimavanserin (34 mg) or placebo. Outcome assessments will occur at 1 week and 1 month following psilocybin administration. The purpose of this study is to clarify the receptor-level mechanisms underlying psilocybin's effects on mood and well-being, along with the associated neurophysiologic signatures. These mechanisms will be examined using psychometric scales, autonomic and fMRI-based neurophysiologic markers, and integrated pharmacokinetic/pharmacodynamic modeling.

Timeline

Start

2026-07

Primary completion

2028-06

Completion

2028-12

Publications

• Background Barrett FS, Doss MK, Sepeda ND, Pekar JJ, Griffiths RR. Emotions and brain function are altered up to one month after a single high dose of psilocybin. Sci Rep. 2020 Feb 10;10(1):2214. doi: 10.1038/s41598-020-59282-y.
• Background Atiq MA, Baker MR, Voort JLV, Vargas MV, Choi DS. Disentangling the acute subjective effects of classic psychedelics from their enduring therapeutic properties. Psychopharmacology (Berl). 2025 Jul;242(7):1481-1506. doi: 10.1007/s00213-024-06599-5. Epub 2024 May 14.
• Background Yaden DB, Griffiths RR. The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacol Transl Sci. 2020 Dec 10;4(2):568-572. doi: 10.1021/acsptsci.0c00194. eCollection 2021 Apr 9.

Drugs

Indications

No indication recorded.