Psilocybin-Assisted Therapy

NCT07332143 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025P013649
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study will examine the safety, tolerability, acceptability, and efficacy of combination psilocybin + psychotherapy to decrease PTSD symptoms. Participants will be randomized into two different treatment groups, allowing the investigators to directly compare PE augmented with psilocybin and psilocybin-assisted psychotherapy.

Conditions

PTSD

Keywords

Psilocybin; PTSD; Supportive therapy; PE therapy

Outcome Measures

Primary Outcomes (3)

• Change in PTSD symptoms based on CAPS-5-R total severity score

  PTSD symptoms will be evaluated using the Revised Clinician-Administered PTSD Scale for DSM-5, that refers to 20 core symptoms as CAPS-5, each rated on a 0-4 severity scale (0 = absent to 4 = extremely severe), combining frequency and intensity. Total possible score range is 0 to 80 with higher scores correlating with worse outcome.

  Baseline, 1-month post-intervention

• Change in PCL-5 score

  The PCL-5 is a 20-item self-report measure of DSM-5 PTSD symptoms. Scores on the PCL range from 0 to 80, with higher scores indicating higher symptom severity, and a cutoff of 33 indicating clinical levels of PTSD symptoms.

  Baseline, 1, 6 and 12 months post-intervention

• Depression symptoms (PHQ-9)

  The PHQ-9 is a 9-item self-report measure of depressive symptoms. A score of 10 or above indicative of a possible major depressive episode, and it provides a measure of severity of these symptoms. Total possible score range is 0-29, higher score correlates with worse outcome.

  Baseline, 1, 6 and 12 months post-intervention

Study Arms (2)

Group 1: Psilocybin combined with supportive therapy

EXPERIMENTAL

All participants will receive a single 25 mg dose of psilocybin during the experimental session, which occurs during to their respective therapy model. Then, participants will receive 2 support (integrative) therapy sessions that will be 1 week apart. In between these sessions, subjects will complete a series of online surveys to track treatment progress.

Drug: psilocybin; Behavioral: Supportive Therapy

Group 2: Psilocybin combined with massed prolonged exposure (PE) therapy

EXPERIMENTAL

All participants will receive a single 25 mg dose of psilocybin during the experimental session, followed by 10 prolonged exposure (PE) therapy sessions for 10 days. In between these sessions, participants will complete a series of online surveys to track treatment progress.

Drug: psilocybin; Behavioral: Prolonged Exposure Therapy

Interventions

psilocybin DRUG

25 mg

Also known as: 3-[2-(Dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate

Group 1: Psilocybin combined with supportive therapy; Group 2: Psilocybin combined with massed prolonged exposure (PE) therapy

Supportive Therapy BEHAVIORAL

Treatment includes non-directive psychological support across the preparatory, dosing, and integration sessions. Preparatory sessions include psychoeducation regarding psilocybin's subjective effects and establish strategies for psilocybin related support, including boundaries around physical touch. Therapists encourage setting intention for dosing day, and practicing experiential exercises. Integration sessions include processing the participant's experience of their psilocybin administration session. Therapists will support participants in identifying activities for ongoing integration outside of sessions. The standard care for supportive therapy will be modeled in this study.

Group 1: Psilocybin combined with supportive therapy

Prolonged Exposure Therapy BEHAVIORAL

Prolonged Exposure (PE) Therapy will be conducted for 10 sessions. They will consist of repeated exposures to trauma memories (imaginal exposure) consistent with the manualized protocol for massed exposure therapy. Also consistent with this treatment manual, participants will listen to imaginal exposures and conduct in real life exposures outside of PE sessions for "homework". The standard care for PE therapy will be modeled in this study.

Group 2: Psilocybin combined with massed prolonged exposure (PE) therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet criteria for PTSD due to trauma occurring at least 3 months prior based on CAPS-5-R diagnostic scoring rules.
• Able to speak and read English (due to standardization of outcome measures).
• Willingness of participant to sign a release for the investigators to communicate with their primary care or mental health providers, if indicated
• Are 18 years and older.
• Are able to swallow pills.
• Agree to have study visits video and/or audio recorded, including Medicine Session, Independent Rater assessments, and non-drug psychotherapy sessions.
• Must provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
• If able to become pregnant, participants must have a negative pregnancy test prior to study entry, at study entry, and prior to each Medicine Session. They must agree to use highly effective birth control for a month prior to the Medicine session and through 10 days after the Medicine session.
• Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to Medicine Session, not participate in any other interventional clinical trials during the duration of the treatment, and agree not to operate their vehicles (or heavy machinery) up to 24 hours after Medicine Session, and commit to medication dosing, therapy, and study procedures.

You may not qualify if:

• Are not able to give adequate informed consent.
• Have a family history bipolar disorder type 1 or a psychotic disorder in first degree relatives.
• Have any current problem which, in the opinion of the investigator or Medical Monitor, might interfere with participation.
• Have hypersensitivity to any ingredient of the IMP (Investigational Medicinal Product).
• Have a history of or current bipolar type 1 disorder, primary psychotic disorder (e.g., schizophrenia), or secondary psychotic features (i.e., Major Depressive disorder with psychotic features.
• Have met criteria at any time during their life for amphetamine or cocaine substance use disorder or any drug of abuse the study physician determines to be unfit for the study.
• Meet criteria for current (past 3 months) moderate or severe substance use disorder, as defined by 4 or more DSM SUD criteria symptoms.
• Have a positive screen for any drug of abuse (amphetamines, etc.) on drug test administered in local community or on site unless being taken as prescribed by a physician.
• Any participant presenting current serious suicide risk, as determined through psychiatric interview and clinical judgment of the investigator will be excluded;
• Suicidal ideation score of 4 or greater within the last 6 months.
• Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment
• Require ongoing concomitant therapy with a psychiatric medication with exceptions described in protocol section on Concomitant Medications.
• Medical History
• Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate, or any medical condition the study physician believes would pose a safety risk or interfere with the effects of the treatment.
• This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, or aneurysm.

Sponsors & Collaborators

• Emory University: lead
• Georgia Department of Veterans Services: collaborator

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Psilocybin; Palliative Care

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Anna Wise, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Wise, PhD

CONTACT

404-712-1035; patstudy@emory.edu

Jessica Maples-Keller, PhD

CONTACT

404-778-2075; jmaple2@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 8, 2026
• First Posted: January 12, 2026
• Study Start: June 8, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: October 1, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)