NCT06592833

Psilocybin With Pimavanserin Compared to Psilocybin Alone for the Treatment of Major Depressive Disorder

Investigating the Role of Serotonin in the Mechanism of Action of Psilocybin in Patients With Major Depressive Disorder

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Icahn School of Medicine at Mount Sinai · Academic / Other
• Sex: All
• Age: 21 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is an interventional, parallel arm assignment treatment study in individuals with Major Depressive Disorder (MDD). Each individual will be treated with a single dose of pimavanserin or placebo plus a single dose of psilocybin. Evaluations will be taken before dosing and following dosing at several timepoints up to 5 weeks post-dosing.

Detailed description

In this study, the researchers want to probe the role of the 5-HT2A receptor in mediating the subjective effects of psilocybin. While previous studies have shown that blockage of the 5-HT2A receptor reduces the psychedelic experience in humans, an animal study revealed that blockage of the 5- HT2A receptor abolished the psychedelic effects without affecting the antidepressant response. This suggests that the pathway responsible for the antidepressant response is dissociated from the psychedelic experience pathway, which is mediated by 5-HT2A signaling.

Conditions

• Major Depressive Disorder

Interventions

Type	Name	Description
DRUG	Psilocybin	Psilocybin, 25mg, given once orally.
DRUG	Pimavanserin	Pimavanserin, 34mg, given once orally
DRUG	Placebo	Matching placebo.

Timeline

• Start date: 2025-02-25
• Primary completion: 2028-03-01
• Completion: 2028-03-01
• First posted: 2024-09-19
• Last updated: 2025-05-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study