Safety and Tolerability of Psilocybin in Post-Traumatic Stress Disorder

January 2, 2024 updated by: Johns Hopkins University
The purpose of this study is to evaluate the safety, tolerability, and potential efficacy of psilocybin-assisted psychotherapy to reduce post-traumatic stress disorder (PTSD) severity in a sample of individuals with PTSD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The proposed Phase I study aims to evaluate the safety, tolerability, and potential efficacy of psilocybin-assisted psychotherapy to reduce PTSD severity in a sample of individuals with PTSD. A sample of up to 30 individuals with PTSD will be recruited. All participants will receive the intervention, which will consist of three psilocybin sessions with an interval of approximately 2 weeks between each session. A 3+3 Phase I trial design will be used to evaluate a range of possible dose sequences with doses ranging from 15 mg up to 45 mg. Safety, tolerability, and efficacy endpoints will be evaluated 2 weeks following each psilocybin session and at 1-month, 3-month, and 6-month follow-ups.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Matthew W Johnson, Ph.D.
  • Phone Number: 410-550-0056
  • Email: mwj@jhu.edu

Study Contact Backup

  • Name: Gideon P Naudé, Ph.D.
  • Phone Number: 410-550-2774
  • Email: gnaude1@jhmi.edu

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 to 80 years old. Participants up to 80 years old who otherwise meet safety criteria will be included to ensure generalizability to the broader clinical population of people with PTSD. Prior work (Griffiths et al. 2016) by our research team administering psilocybin to older cancer patients using the same upper age limit in the inclusion/exclusion criteria (i.e., 80 years old) found a comparable risk profile for psilocybin to research conducted with younger patients. Although it is possible that older patients experience diminished serotonin 2A (5-HT2A) receptor expression resulting in a lower/less intense response to psilocybin, this information will be important to gather in this Phase I context.
  • Have given written informed consent
  • Read, write, and speak English
  • At Screening, meet Diagnostic and Statistical Manual-5th edition (DSM-5) criteria for current PTSD with a symptom duration of 6 months or longer according to the Clinician-Administered PTSD Scale for DSM-5
  • Able to complete the study measures
  • Previously sought treatment for PTSD (e.g., prolonged exposure therapy, cognitive processing therapy, sertraline, paroxetine)
  • Be otherwise medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests (Complete Blood Count, Comprehensive Metabolic Panel, urine beta-human chorionic gonadotropin, urine toxicology screen).

Exclusion Criteria:

  • Current physical dependence (as evidenced by self-reported withdrawal symptoms) on a drug other than caffeine or nicotine
  • Seizure disorder
  • Receiving current treatment for PTSD
  • Cardiovascular conditions: angina, a clinically significant ECG abnormality (e.g. atrial fibrillation or corrected QT interval >450msec), transient ischemic attack (TIA) in the last 6 months, stroke, or uncontrolled hypertension with resting blood pressure systolic >150 or diastolic >95.
  • Recent (<1year) intracranial or subarachnoid hemorrhage, ischemic stroke, TIA
  • Pulmonary disease: chronic obstructive pulmonary disease, active asthma (inhaler use in last 6 months)
  • Diabetes mellitus treated with insulin or oral hypoglycemic agents
  • Current suicidal ideation or suicidality
  • Current engagement in evidence-based PTSD therapy/treatment (prior to psilocybin session)
  • Women: Pregnancy (pregnancy tests will be conducted for women during screen and prior to experimental sessions).
  • Current or past history of meeting DSM-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder.
  • Currently taking efavirenz or serotonin-acting dietary supplements (e.g., 5-hydroxy- tryptophan, St. John's wort).
  • Currently taking antidepressants of any drug class, antipsychotics, or monoamine oxidase inhibitors.
  • Recent (within past 12 months) or extensive history of hallucinogen use (>20 lifetime uses).
  • Moderate or severe DSM-5 Substance Use Disorder in the past five years (excluding tobacco and caffeine)
  • Family (i.e., 1st degree relative) history of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder.
  • For the final (5th) dose sequence (35, 40, and 45 mg) participants that weigh less than 50 kg

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Sequence 1 (15, 20, 25)

Psilocybin dose sequence

Session 1: 15 mg Session 2: 20 mg Session 3: 25 mg
Drug: Psilocybin
Participants will receive three psilocybin sessions, at least two weeks apart.
Experimental: Dose Sequence 2 (20, 25, 30)

Psilocybin dose sequence

Session 1: 20 mg Session 2: 25 mg Session 3: 30 mg
Drug: Psilocybin
Participants will receive three psilocybin sessions, at least two weeks apart.
Experimental: Dose Sequence 3 (25, 30, 35)

Psilocybin dose sequence

Session 1: 25 mg Session 2: 30 mg Session 3: 35 mg
Drug: Psilocybin
Participants will receive three psilocybin sessions, at least two weeks apart.
Experimental: Dose Sequence 4 (30, 35, 40)

Psilocybin dose sequence

Session 1: 30 mg Session 2: 35 mg Session 3: 40 mg
Drug: Psilocybin
Participants will receive three psilocybin sessions, at least two weeks apart.
Experimental: Dose Sequence 5 (35, 40, 45)

Psilocybin dose sequence

Session 1: 35 mg Session 2: 40 mg Session 3: 45 mg
Drug: Psilocybin
Participants will receive three psilocybin sessions, at least two weeks apart.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Peak Post-Administration Blood Pressure
Time Frame: Approximately 1.5 - 2 months
Blood pressure will be monitored at 30, 60, 90, 120, 180, 240, 300, and 360 minutes after capsule administration. Mean peak blood pressure across the 3 psilocybin sessions will be used as the outcome measure.
Approximately 1.5 - 2 months
Mean Peak Post-Administration Heart Rate
Time Frame: Approximately 1.5 - 2 months
Heart rate will be monitored at 30, 60, 90, 120, 180, 240, 300, and 360 minutes after capsule administration. The mean peak heart rate across the 3 psilocybin sessions will be used as the outcome measure.
Approximately 1.5 - 2 months
Mean Pre-Administration Suicide Ideation Scores (Columbia Suicide Severity Rating Scale - Severity Factor)
Time Frame: Approximately 3 weeks
The Columbia Suicide Severity Rating Scale will be used to assess baseline severity of suicide ideation. Scores on the Severity subscale range from 1 - 5, where 1= "wish to be dead"; 2 = "nonspecific active suicidal thoughts"; 3 = "suicidal thoughts with methods"; 4 = "suicidal intent"; and 5 = "suicidal intent with plan". The mean of the Severity subscale scores from the 3 preparation visits will be used as the outcome measure.
Approximately 3 weeks
Mean Change in Suicide Ideation Scores (Columbia Suicide Severity Rating Scale - Severity Factor)
Time Frame: Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration
The Columbia Suicide Severity Rating Scale will be used to assess post-administration severity of suicide ideation. Scores on the Severity subscale range from 1 - 5, where 1= "wish to be dead"; 2 = "nonspecific active suicidal thoughts"; 3 = "suicidal thoughts with methods"; 4 = "suicidal intent"; and 5 = "suicidal intent with plan". The mean change in Severity subscale scores between the preparation visits and the integration visits will be used as the outcome measure.
Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change in Clinician-Administered PTSD Scale for DSM-5 scores
Time Frame: Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a semi-structured interview that assesses history of DSM-5-defined traumatic event exposure, including the most distressing event, time since exposure, to produce a diagnostic score (presence vs. absence) and a PTSD Total Severity score. The mean of the Total Severity scores from the 3 integration visits will be used as the outcome measure.
Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration
Mean Change in PTSD Checklist Scores
Time Frame: Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration
The PTSD Checklist (PCL-5) is a 20-item self-report questionnaire in which respondents indicate the presence and severity of PTSD symptoms according to diagnostics in the DSM-5. Participants indicate how much distress they have experienced due to symptoms such as "Trouble remembering important parts of a stressful experience from the past" and "Feeling irritable or having angry outbursts" on a five-point Likert-type scale (1=Not at all to 5=Extremely). The mean of the PCL-5 scores from the 3 integration visits will be used as the outcome measure.
Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Matthew W Johnson, Ph.D., Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 28, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 3, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 5, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00288303

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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