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

NCT06592833 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY-23-00855
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Mystical Experience Questionnaire (MEQ-30) Score

  Acute subjective effects of psilocybin measured by the Mystical Experience Questionnaire (MEQ-30). Full Scale ranges from 0 to 150, with higher scores indicating more mystical experience.

  6 hours post-treatment

Secondary Outcomes (1)

• Montgomery-Åsberg Depression Rating Scale (MADRS) Score

  7 days after dosing

Study Arms (2)

Psilocybin + Pimavanserin

ACTIVE COMPARATOR

single dose Psilocybin and single dose Pimavanserin

Drug: Psilocybin; Drug: Pimavanserin

Psilocybin + Placebo

PLACEBO COMPARATOR

single dose Psilocybin and single dose Placebo

Drug: Psilocybin; Drug: Placebo

Interventions

Psilocybin DRUG

Psilocybin, 25mg, given once orally.

Psilocybin + Pimavanserin; Psilocybin + Placebo

Pimavanserin DRUG

Pimavanserin, 34mg, given once orally

Also known as: Nuplazid

Psilocybin + Pimavanserin

Placebo DRUG

Matching placebo.

Psilocybin + Placebo

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-80 years, any gender
• Current primary diagnosis of Unipolar Major Depressive Disorder (MDD) without psychotic features using DSM-5 criteria
• item Hamilton Rating Scale for Depression (HRSD) ≥16
• Current diagnosis of Major Depressive Episode (MDE)
• Capable of providing informed consent and complying with study procedures
• Currently using or agreeing to use a highly effective contraception, if person of childbearing potential (such as condoms, IUD, or oral contraceptive), for duration of the study. Male participants agree to use highly effective contraception with partners of childbearing potential
• Discontinuation of any serotonergic drug for at least 2 weeks or 5 half-lives (whichever of the two is longer) prior to psilocybin exposure

You may not qualify if:

• Any severity of substance use disorder in the last 6 months (excluding tobacco use disorder) as determined by DSM-V criteria via the SCID
• Current psychiatric hospitalization or psychiatric hospitalization within the last 6 months
• Use of psychedelics in the last 12 months
• Non-medical or illicit use of ketamine in the past 12 months
• Negative reaction after prior use of psychedelics
• Past or current psychotic disorder (including psychotic MDD), mania, or bipolar disorder
• Severe depression as indicated by Clinical Global Impressions (CGI)-Severity score ≥ 5 at baseline
• Significant suicidal ideation as indicated by C-SSRS \> 2 in the past 6 months at time of screening
• Suicide attempt in the past 2 years, or clinician concern that the patient poses a risk to self or others
• Acute, severe, or unstable medical illness
• Weight \> 300 lbs., or girth size incompatible with scanner bore
• Any conditions/qualities that make participation in MRI imaging unsafe\*
• Any physical or intellectual disability adversely affecting ability to complete assessments.
• Current pregnancy or currently breast feeding.
• Any clinically significant abnormal lab test result, including clinically significant abnormal baseline liver and/or renal function tests

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai, Center for Psychedelic Therapy Research

New York, New York, 10025, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Psilocybin; pimavanserin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• James Murrough

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Rachel Fremont

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Depression and Anxiety Center Icahn School of Medicine at Mount Sinai

CONTACT

(212) 241-6539; dac@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: September 19, 2024
• Study Start: February 25, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)