RECRUITING

Psilocybin Mechanism of Action (MOA)

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2025-02

Study Completion:2028-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06592833

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:21 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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 * Active suicidal ideation as indicated by C-SSRS \> 2 in the past 6 months at time of screening * Suicide attempt requiring hospitalization in the past 2 years, or clinician concern that the patient poses a risk to self or others * History of mania * Acute, severe, or unstable medical illness, including clinical or laboratory evidence of renal and/or hepatic impairment * 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 abnormal lab test result (including abnormal baseline liver 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/torsade 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

Inclusion Criteria

Exclusion 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

* 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
* Active suicidal ideation as indicated by C-SSRS \> 2 in the past 6 months at time of screening
* Suicide attempt requiring hospitalization in the past 2 years, or clinician concern that the patient poses a risk to self or others
* History of mania
* Acute, severe, or unstable medical illness, including clinical or laboratory evidence of renal and/or hepatic impairment
* 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 abnormal lab test result (including abnormal baseline liver 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/torsade 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

Contacts and Locations

Study Contact

Esther Lee

CONTACT

212-585-6133

esther.lee@mssm.edu

Esha Talati

CONTACT

esha.talati@mssm.edu

Principal Investigator

James Murrough

PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Rachel Fremont

PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Study Locations (Sites)

Center for Psychedelic Therapy Research

New York, New York, 10025

United States

Collaborators and Investigators

Sponsor: Icahn School of Medicine at Mount Sinai

James Murrough, PRINCIPAL_INVESTIGATOR, Icahn School of Medicine at Mount Sinai
Rachel Fremont, PRINCIPAL_INVESTIGATOR, Icahn School of Medicine at Mount Sinai

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02

Study Completion Date2028-03

Study Record Updates

Study Start Date2025-02

Study Completion Date2028-03

Terms related to this study

Additional Relevant MeSH Terms

Major Depressive Disorder