NCT06592833 · Icahn School of Medicine at Mount Sinai
Psilocybin With Pimavanserin Compared to Psilocybin Alone for the Treatment of Major Depressive Disorder
What this study is about
This is an interventional, parallel treatment group$1 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.
View original scientific description
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.
Interventions
DRUG
Psilocybin
Psilocybin, 25mg, given once orally.
DRUG
Pimavanserin
Pimavanserin, 34mg, given once orally
DRUG
Placebo
Matching placebo.
Primary outcome measures
Mystical Experience Questionnaire (MEQ-30) Score
Time frame: 6 hours post-treatment
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- New York, New York
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 14, 2025 · Source of record for eligibility and locations