Recruiting
Phase 2

Psilocybin

Sponsor:

Icahn School of Medicine at Mount Sinai

Code:

NCT06592833

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

Interventions

Psilocybin

Pimavanserin

Placebo

Study Details

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

Study ID

NCT06592833

Start date

Feb 25, 2025

Status verified date

May, 2025

Completion date

Mar 1, 2028

Anticipated

Primary completion date

Mar 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age 21-80 years, any gender
  • Current primary diagnosis of Unipolar Major Depressive Disorder (MDD) without psychotic features using DSM-5 criteria
  • 24-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

Exclusion Criteria:

  • 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
  • Currently being treated with a contraindicated medication. Contraindicated medications include antipsychotic medications, serotonergic antidepressant medications, and mood stabilizers that may attenuate the effects of psilocybin. Strong CYP3A4 inhibitors and inducers are also contraindicated. UGT1A9 and UGT1A10 inhibitors, monoamine oxidase, and aldehyde or alcohol dehydrogenase inhibitors are prohibited concomitant medications.
  • History of abnormal QT prolongation or QTc interval >450 ms on screening
  • Use of medications known to prolong the QT interval
  • Any congenital prolongation of the QT interval or a family history of long QT syndrome
  • A family history of sudden cardiac or unexplained death
  • A family history in a first-degree relative of psychosis/schizophrenia or related disorders
  • A first-degree family history of bipolar disorder
  • A history of cardiac arrhythmias or who require treatment with an antiarrhythmic medication
  • A history of any cardiovascular disorder/condition known to increase the possibility of QT prolongation, or any other risk factors for prolonged QT interval/tosades de pointes (including symptomatic bradycardia, hypokalemia, hypomagnesemia, hypocalcemia, heart failure, or Brugada Syndrome)
  • Preexisting cardiovascular conditions, including cardiac valvulopathy, pulmonary hypertension, hypertension, tachycardia, and any cardiovascular conditions that may be worsened/exacerbated by elevated blood pressure or heart rate.
  • Baseline vital sign parameters at screening and on day of dosing prior to dose that exceed to the following values for systolic blood pressure (SBP), diastolic (DBP), and heart rate (HR): SBP > 139 mmHg, DBP 89 mmHg, and HR > 90 bpm
  • Hypersensitivity to either psilocybin or pimavanserin
  • Psychiatric or other condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin
  • Positive urine toxicology at screening
  • Any clinically significant abnormalities on 12-lead electrocardiogram (ECG)
  • Mini-Mental State Examination (MMSE) score < 25
  • Brief Psychiatric Rating Scale (BPRS-6) > 5
  • Potential fall risk

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Psilocybin + Pimavanserin

single dose Psilocybin and single dose Pimavanserin

placebo comparator: Psilocybin + Placebo

single dose Psilocybin and single dose Placebo

Interventions

Psilocybin

Psilocybin, 25mg, given once orally.

Pimavanserin

Pimavanserin, 34mg, given once orally

Placebo

Matching placebo.

Primary outcome measure

  • Mystical Experience Questionnaire (MEQ-30) Score [ Time Frame: 6 hours post-treatment ]

Central Contacts and Locations

Central contacts

Depression and Anxiety Center Icahn School of Medicine at Mount Sinai

(212) 241-6539dac@mssm.edu

Locations

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

Recruiting

New York, New York, United States, 10025

Contacts

Depression and Anxiety Center

212-241-6539dac@mssm.edu

Principal Investigator:

James Murrough

More Information

Sponsor

Icahn School of Medicine at Mount Sinai

Last update posted

May 14, 2025

Last verified

May, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Icahn School of Medicine at Mount Sinai on 2025-05-14.