Open-Label Psilocybin Study in Transdiagnostic Population

NCT06442423 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2000037785
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to investigate the safety, feasibility, and tolerability of psilocybin treatment in individuals with functional impairment due to psychiatric symptoms. The secondary objective of this study is to determine whether individuals with functional impairments due to psychiatric symptoms will experience statistically significant symptom reduction and functional improvement from baseline symptom measurements (Visit 3) to 1-week (Visit 7), 4-weeks (Visit 8), and 6-weeks (Visit 9) post dosing. The investigators will recruit individuals with mood, anxiety, trauma, addictive, or related symptomatology, and who have functional impairment associated with these symptoms. A DSM-5 diagnosis is not required (nor is it an exclusion). The investigators will allow for comorbidity and only exclude based on psychological and physiological safety considerations. Critically, this approach will allow us to assess the tolerability of our interventions in individuals who would typically be excluded from efficacy studies due to various comorbid DSM-5 conditions. The investigators will employ an open-label study where participants will be given one dose of oral psilocybin 25mg. The investigators will also have follow-up visits at 1, 4, and 6 weeks and an optional long-term follow-up at 3, 6, and 12 months.

Conditions

Transdiagnostic; Depression - Major Depressive Disorder; Anxiety; PTSD Symptoms; PTSD; Substance Use; Substance Use Disorder (SUD); OCD

Keywords

depression; anxiety; substance use; addiction; PTSD; OCD; psilocybin; psychedelic

Outcome Measures

Primary Outcomes (2)

• Columbia-Suicide Severity Rating Scale (C-SSRS)

  Range 0 to 25, higher score indicating more suicidal risk

  6 weeks

• Adverse Events Log

  This log is cumulative and captures adverse events (including serious adverse events) of all participants throughout the study.

  6 weeks

Secondary Outcomes (36)

• World Health Organization Disability Assessment Schedule 2.0

  6 weeks

• Diagnostic Interview for Anxiety, Mood, and Obsessive-Compulsive and Related Neuropsychiatric Disorders (Self-report and Clinician Administered)

  screening

• Structured Clinical Interview for DSM-5 Personality Disorders (SCID-5-SPQ)

  screening

• Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II) Symptom Checklist and Severity Scale

  6 weeks

• Montgomery-Asberg Depression Scale (MADRS)

  6 weeks

Study Arms (1)

Open-label

OTHER

Psilocybin will be administered in an opaque, size 2 gelatin capsule with approximately 180 ml of water to be orally ingested at Visit 5. The dose of psilocybin will be 25 mg.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Psilocybin will be administered in an opaque, size 2 gelatin capsule with approximately 180 ml of water to be orally ingested at Visit 5. The dose of psilocybin will be 25 mg.This is an open-label clinical trial with a single treatment arm. This is an open-label clinical trial with no blinding.

Open-label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one psychiatric symptom causing functional impairment over the past 30 days as established by a trained rater on the DIAMOND (at least "mild" impairment) and/or the WHODAS-2.0 12-item (a raw score of \>16) - assessment instruments indexing health and disability.
• English fluency - able to understand the process of consent and the risk and benefits associated with the study, and able to provide written (signed and dated) informed consent form.
• Agree to set up safe transportation after leaving the site following the dosing session. Acceptable arrangements include: arranging for a friend/family member to drive them home, pick them up and escort them home; if the participant is unable to arrange for a friend/family member to escort them home, the study staff will arrange private transportation and follow up with the participant to ensure that they arrived at their destination.
• Must be able to identify a physician/treater that can be contacted to further assure that it is safe for the subject to participate and agree to sign a medical release for the investigators to communicate directly with this outside provider to confirm treatment and medical history via phone and/or email.
• Ability to orally ingest pills for psilocybin dosing visit.
• Must provide an adult contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the PI and/or study personnel in the event of an emergency, and who can provide transportation for study visits if necessary and independently comment on any changes in the participant's mood or behavior after the administration of psilocybin. Be medically stable (no medical issues based on physical exam, labs and medical evaluation) as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an ECG, and routine blood and urinalysis laboratory tests (see section 6.3.4 for labs). Must also demonstrate decisional capacity based on clinical assessment ensuring the participant can understand, appreciate, and reason through the study's purpose, procedures, and associated risks, as well as tolerate the potential effects of the study medication.
• Be psychologically stable: Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least one month prior to screening and is expected to remain stable during participation in the study (up to 4-weeks post-dosing).
• If participant is of childbearing potential, must agree to use adequate birth control and not attempt to become pregnant during study up to 4 weeks post dosing session (see Section 6.3.3).
• If participant is of childbearing potential, must have a negative urine pregnancy test at study entry and prior to the dosing session. Participants who are FOCBP must not plan to become pregnant or donate eggs, starting at least 1 month before receiving the trial intervention and for at least 1 week after the final follow-up visit.
• A FOCBP is defined as a female who is considered fertile following menarche and until becoming postmenopausal, unless permanently sterile (see below).
• Females in the following categories are not considered FOCBP:
• Premenarchal.
• Premenopausal with 1 of the following:
• Documented hysterectomy or bilateral salpingectomy/tubal occlusion/oophorectomy.
• Postmenopausal.

You may not qualify if:

• Personal history of a primary psychotic disorder (e.g., schizophrenia, delusional disorder, schizoaffective disorder) or Bipolar I disorder, or at least one first-degree relative with a diagnosis of primary psychotic disorder (e.g., schizophrenia, delusional disorder, schizoaffective disorder) or Bipolar I disorder.
• Active suicidal intent or suicidal or non-suicidal self-injurious behaviors, as defined by a "yes" response to question 4 on C-SSRS within the past 6 months at screening or prior to dosing (Active Suicidal Ideation with Some Intent to Act, with or without Specific Plan).
• Use of a classic psychedelic (i.e., LSD, psilocybin, DMT, mescaline) within the 3 months prior to enrollment (not including microdosing).
• Use of ketamine within the past month at Screening.
• History of regular and frequent use of a classic psychedelic (more than 10 times per year) in a structured, intentional setting over the past 10 years. Structured use refers to participation in organized retreats, ceremonies, or church services. Microdosing is not included.
• History of Other Hallucinogen Use Disorder.
• History of intolerance to drugs known significantly to alter perception (i.e., psilocybin, LSD, salvinorium A, mescaline).
• Patients taking 5-hydroxytryptophan or St. John's Wort
• A positive breathalyzer test
• Changes to psychotropic medication and/or dosages within the past 3 months.
• Current or recent (within 2 weeks of enrollment) prescription of MAOI, Lithium, and/or methadone use.
• Has a psychiatric condition that precludes the establishment of therapeutic rapport as evidenced by long-term patterns of unstable relationships, a history of significant stress- related paranoia, or identity disturbances.
• Use of any other investigational drugs within 30 days prior to Screening.
• Allergy to gelatin.
• Hypertension at screening is defined as: systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg, on the lowest of three measurements.

Sponsors & Collaborators

• Yale University: lead
• Usona Institute: collaborator

Study Sites (1)

Connecticut Mental Health Center - Yale School of Medicine

New Haven, Connecticut, 06519, United States

RECRUITING

MeSH Terms

Conditions

Anxiety Disorders; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Depression; Behavior, Addictive

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Mental Disorders; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Chemically-Induced Disorders; Behavioral Symptoms; Behavior; Compulsive Behavior; Impulsive Behavior

Intervention Hierarchy (Ancestors)

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

Study Officials

• Benjamin Kelmendi, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Gabrielle Agin-Liebes, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Shnayder

CONTACT

(203) 737-3404; enact@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: We will employ an unblinded, open-label study where all participants will be given one dose of oral psilocybin 25mg. We will also have follow-up visits at 1, 4, and 6 weeks and an optional long-term follow-up at 3, 6, and 12 months.

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 4, 2024
• Study Start: October 17, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)