Psilocybin Mechanism of Action (MOA)

Phase 2

Not yet recruiting

• Conditions: Major Depressive Disorder

• Registration Number: NCT06592833
• Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-9-9
• Last Update Posted: 23 September 2024

Recruitment & Eligibility

• Status: Not yet recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Inclusion Criteria:<br><br> - Age 21-80 years, any gender<br><br> - Current primary diagnosis of Unipolar Major Depressive Disorder (MDD) without<br> psychotic features using DSM-5 criteria<br><br> - 24-item Hamilton Rating Scale for Depression (HRSD) =16<br><br> - Current diagnosis of Major Depressive Episode (MDE)<br><br> - Capable of providing informed consent and complying with study procedures<br><br> - Currently using or agreeing to use a highly effective contraception, if person of<br> childbearing potential (such as condoms, IUD, or oral contraceptive), for duration<br> of the study. Male participants agree to use highly effective contraception with<br> partners of childbearing potential<br><br> - Discontinuation of any serotonergic drug for at least 2 weeks or 5 half-lives<br> (whichever of the two is longer) prior to psilocybin exposure<br><br>Exclusion Criteria:<br><br> - Any severity of substance use disorder in the last 6 months (excluding tobacco use<br> disorder) as determined by DSM-V criteria via the SCID<br><br> - Current psychiatric hospitalization or psychiatric hospitalization within the last 6<br> months<br><br> - Use of psychedelics in the last 12 months<br><br> - Non-medical or illicit use of ketamine in the past 12 months<br><br> - Negative reaction after prior use of psychedelics<br><br> - Past or current psychotic disorder (including psychotic MDD), mania, or bipolar<br> disorder<br><br> - Severe depression as indicated by Clinical Global Impressions (CGI)-Severity score =<br> 5 at baseline<br><br> - Active suicidal ideation as indicated by C-SSRS > 2 in the past 6 months at time of<br> screening<br><br> - Suicide attempt requiring hospitalization in the past 2 years, or clinician concern<br> that the patient poses a risk to self or others<br><br> - History of mania<br><br> - Acute, severe, or unstable medical illness, including clinical or laboratory<br> evidence of renal and/or hepatic impairment<br><br> - Weight > 300 lbs, or girth size incompatible with scanner bore<br><br> - Any conditions/qualities that make participation in MRI imaging unsafe*<br><br> - Any physical or intellectual disability adversely affecting ability to complete<br> assessments.<br><br> - Current pregnancy or currently breast feeding.<br><br> - Any abnormal lab test result (including abnormal baseline liver function tests)<br><br> - Currently being treated with a contraindicated medication. Contraindicated<br> medications include antipsychotic medications, serotonergic antidepressant<br> medications, and mood stabilizers that may attenuate the effects of psilocybin.<br> Strong CYP3A4 inhibitors and inducers are also contraindicated. UGT1A9 and UGT1A10<br> inhibitors, monoamine oxidase, and aldehyde or alcohol dehydrogenase inhibitors are<br> prohibited concomitant medications.<br><br> - History of abnormal QT prolongation or QTc interval >450 ms on screening<br><br> - Use of medications known to prolong the QT interval<br><br> - Any congenital prolongation of the QT interval or a family history of long QT<br> syndrome<br><br> - A family history of sudden cardiac or unexplained death<br><br> - A family history in a first-degree relative of psychosis/schizophrenia or related<br> disorders<br><br> - A first-degree family history of bipolar disorder<br><br> - A history of cardiac arrhythmias or who require treatment with an antiarrhythmic<br> medication<br><br> - A history of any cardiovascular disorder/condition known to increase the possibility<br> of QT prolongation, or any other risk factors for prolonged QT interval/torsade de<br> pointes (including symptomatic bradycardia, hypokalemia, hypomagnesemia,<br> hypocalcemia, heart failure, or Brugada Syndrome)<br><br> - Preexisting cardiovascular conditions, including cardiac valvulopathy, pulmonary<br> hypertension, hypertension, tachycardia, and any cardiovascular conditions that may<br> be worsened/ exacerbated by elevated blood pressure or heart rate.<br><br> - Baseline vital sign parameters at screening and on day of dosing prior to dose that<br> exceed to the following values for systolic blood pressure (SBP), diastolic (DBP),<br> and heart rate (HR): SBP > 139 mmHg, DBP 89 mmHg, and HR > 90 bpm<br><br> - Hypersensitivity to either psilocybin or pimavanserin<br><br> - Psychiatric or other condition judged to be incompatible with establishment of<br> rapport with therapy team and/or safe exposure to psilocybin<br><br> - Positive urine toxicology at screening<br><br> - Any clinically significant abnormalities on 12- lead electrocardiogram (ECG)<br><br> - Mini-Mental State Examination (MMSE) score < 25<br><br> - Brief Psychiatric Rating Scale (BPRS-6) > 5<br><br> - Potential fall risk

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mystical Experience Questionnaire (MEQ-30) Score

Secondary Outcome Measures

Name	Time	Method
Montgomery-Åsberg Depression Rating Scale (MADRS) Score