Psilocybin-Assisted Randomized Therapy

NCT ID: NCT07332143

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-03-31

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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The Primary objective is to pilot and investigate tolerability, safety, and acceptability of psilocybin-assisted supportive therapy and psilocybin-assisted massed prolonged exposure (PE) therapy and conduct exploratory analyses related to comparative effectiveness of these treatments, including preliminary outcomes from pre-treatment to 1-month follow-up on post-traumatic stress disorder (PTSD) symptoms. Safety and tolerability of the treatment will be assessed and evaluated using the Swiss Psychedelic Side Effects Inventory (SPSI), Psychedelic-assisted Therapy After Effects (PATAE), and the Accessibility Questionnaire (AQ).

The study will also evaluate the effect of psilocybin and massed exposure therapy using Subjective Units of Distress (SUDS) during imaginal exposure sessions; to assess self-reported PTSD and depression symptoms across treatment and investigate effect on fear extinction learning and fear extinction recall as assessed via fear potentiated startle. Given that this is a pilot study with small sample, analyses will be preliminary.

Conditions

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PTSD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1: Psilocybin combined with supportive therapy

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.

Group Type EXPERIMENTAL

psilocybin

Intervention Type DRUG

25 mg

Supportive Therapy

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

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.

Group Type EXPERIMENTAL

psilocybin

Intervention Type DRUG

25 mg

Prolonged Exposure Therapy

Intervention Type 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.

Interventions

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psilocybin

25 mg

Intervention Type DRUG

Supportive Therapy

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.

Intervention Type BEHAVIORAL

Prolonged Exposure Therapy

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.

Intervention Type BEHAVIORAL

Other Intervention Names

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

Eligibility Criteria

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Inclusion Criteria

1. Meet criteria for PTSD due to trauma occurring at least 6 months prior based on CAPS-5-R diagnostic scoring rules.
2. Willingness of participant to sign a release for the investigators to communicate with their primary care or mental health providers, if indicated
3. Are 18 years and older.
4. Are able to visually read and understand the English language and give written informed consent.
5. Are able to swallow pills.
6. Agree to have study visits video and/or audio recorded, including dosing session, Independent Rater assessments, and non-drug psychotherapy sessions.
7. 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.
8. Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
9. If able to become pregnant, must have a negative pregnancy test prior to study entry, at study entry, and prior to the psilocybin Session. They must agree to use highly effective birth control for a month prior to the psilocybin session and through 10 days after the Medicine session. Highly effective birth control methods include intrauterine device, injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Not able to become pregnant is defined as permanent sterilization, postmenopausal (i.e., 12 consecutive months without menstruation), or assigned male at birth.
10. Agree to the following lifestyle modifications: comply with requirements for fasting and refraining from certain medications prior to the psilocybin Session, not participate in any other interventional clinical trials during the duration of the treatment, and be accompanied to hotel after Medicine Session, and commit to medication dosing, therapy, and study procedures.

Exclusion Criteria

Potential participants are ineligible to enroll in the protocol if they:

1. Are not able to give adequate informed consent.
2. Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders. "Compensation litigation" will not include veterans who are service connected through PTSD or other conditions.
3. Are likely, in the investigator's opinion and via observation during the Preparatory Period, to be re-exposed to their index trauma or other significant trauma, lack social support, or lack a stable living situation.
4. Have any current problem which, in the opinion of the investigator or Medical Monitor, might interfere with participation.
5. Have a family history bipolar disorder type 1 or a psychotic disorder in first degree relatives.
6. Have a history of or current bipolar type 1 disorder, or primary psychotic disorder (e.g., schizophrenia), as assessed via DIAMOND and clinical interview, dementia; or intellectual disability.
7. Have current major depressive disorder with psychotic features assessed via DIAMOND.
8. Have met criteria at any time during their life for hallucinogen substance use disorder.
9. Meet criteria for current (past 3 months) moderate or severe substance use disorder, as defined by 4 or more DSM SUD criteria symptoms.
10. Have a positive screen for cocaine or amphetamines on drug test administered in local community or on site unless being taken as prescribed by a physician.
11. Have current clinically relevant personality pathology.
12. Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled. Any participant presenting with the following on the C-SSRS administered at screening or baseline will be excluded:

1. Suicidal ideation score of 4 or greater within the last six months.
2. Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment
13. Require ongoing concomitant therapy with a psychiatric medication with exceptions described in protocol section on Concomitant Medications.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Georgia Department of Veterans Services

UNKNOWN

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role lead

Responsible Party

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Anna Wise

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anna Wise, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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Emory University Hospital

Atlanta, Georgia, United States

Site Status

Countries

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United States

Central Contacts

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Anna Wise, PhD

Role: CONTACT

404-727-4592

Jessica Maples-Keller, PhD

Role: CONTACT

404-778-2075

Facility Contacts

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Anna Wise, PhD

Role: primary

404-727-4592

Jessica Maples-Keller, PhD

Role: backup

404-778-2075

Other Identifiers

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2025P013649

Identifier Type: -

Identifier Source: org_study_id

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