A Study of Psilocybin for PTSD

Post Traumatic Stress Disorder Clinical Trial

Official title:

Psilocybin for PTSD With or Without Psychotherapy: A Pilot Study of Safety and Efficacy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06407635
• Other study ID #: IRB00407008
• Status: Recruiting
• Phase: Phase 1
• Start date: June 7, 2024
• Est. completion date: May 2027

Study information

• Verified date: June 2024
• Source: Johns Hopkins University
• Contact: Brandon Weiss, PhD
• Phone: 410-550-0048
• Email: brandon[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proposed open-label, controlled study at the Johns Hopkins Center for Psychedelic and Consciousness Research (CPCR) will test the following primary hypotheses in adult patients with chronic PTSD who are currently taking a serotonin reuptake inhibitor: psilocybin therapy will be feasible and safe for participants, significantly remediate PTSD symptoms, and enhance wellbeing and quality of life. In addition, the study will examine whether elements of evidence-based trauma-focused psychotherapy enhance treatment response when paired with psilocybin.

Description:

This study uses a randomized controlled design to compare the safety and efficacy of 2 doses of psilocybin for PTSD. In addition, it will investigate the effects of trauma-focused psychotherapy (which includes standard psychological support) versus standard psychological support alone. Twenty participants will be recruited. Following the first psilocybin session, participants will be randomized to either the trauma-focused psychotherapy (which includes standard psychological support) treatment condition or the standard psychological support treatment condition (the latter being typical for the experimental administration of psilocybin therapy). Both groups will receive identical treatment prior to receiving the first dose of psilocybin, with one group receiving procedures related to trauma-focused psychotherapy (combined with standard psychological support) beginning after receipt of psilocybin. The study will include clinician and participant ratings of PTSD and mood symptoms pre- and post-drug session and monitor and participant ratings of subjective drug effects during and after each drug session.

The intervention for both groups will consist of about 8 hours of preparatory meetings (over approximately 2 weeks), followed by 2 psilocybin sessions separated by approximately 2 weeks. The initial psilocybin dose will be 25 mg. The dose for the second session may be increased conditional on the strength of subjective effects, as measured by the Mystical Experiences Questionnaire (MEQ30), taken at the end of participants' first psilocybin session. This allows a dose to increase if, for example, concomitant serotonin reuptake inhibitors reduce subjective effects. Participants with a score ≥60% of the maximum on the MEQ30 will remain at a dose of 25 mg of psilocybin for the second session. Participants with an MEQ30 score below 60% will receive a dose of 40 mg for the second session. Elevation of dose will also be based on the clinical judgment of the principal investigator, study physician, and study staff that a higher dose can be safely administered. In addition, participants who prefer to not elevate the dose will remain at 25 mg for the second session.

To support the participant's therapeutic integration of psilocybin experiences, following each psilocybin session, participants will meet with the session facilitator(s) at multiple scheduled time points. Additional contact hours will be scheduled if it is judged that the participant would benefit from additional meetings to discuss experiences from the session(s) or to prepare for the next session.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

Inclusion Criteria:

• 21 to 75 years old

• Have given written informed consent

• Have a confirmed DSM-5 diagnosis of Post-Traumatic Stress Disorder with symptom duration >= 6 months

• Have a baseline CAPS-5 score of >=35

• Currently taking a serotonin reuptake inhibitor (e.g. selective serotonin reuptake inhibitor (SSRI), serotonin and norepinephrine reuptake inhibitor (SNRI), at a stable dose for at least two weeks.

• Be judged by study team clinicians to be at low acute risk for suicidality

• Be 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

• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.

• Agree to refrain from using any psychoactive drugs, including alcoholic beverages within 24 hours of each drug administration. The exception is caffeine and nicotine.

• Agree not to take any as needed (PRN) medications on the mornings of drug sessions

• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.

• Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.

• Have limited lifetime use of hallucinogens (the following criteria are preferred: no use in the past 2 years; total hallucinogen use less than 10 times)

• Have at least a high school level of education or equivalent (e.g. GED).

• Weigh between 40kg - 120kg.

• (for female participants) Agree to use highly effective birth control measure within two weeks of completing the dosing sessions.

(for male participants) Agree to use contraception and refrain from sperm donation within two weeks of completing dosing sessions, as the reproductive safety for psilocybin is not yet established.

Exclusion Criteria:

General medical exclusion criteria:

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control.

• Cardiovascular conditions: coronary artery disease, stroke, angina, hypertension with resting blood pressure systolic >139 or diastolic >89, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged corrected QT interval (i.e., heart-rate corrected QT interval (QTc) > 450 msec), artificial heart valve, or transient ischemic attack (TIA) in the past year

• Epilepsy with history of seizures

• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia

• Currently taking a Monoamine Oxidase Inhibitor

Psychiatric Exclusion Criteria:

• Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder

• Current or history within one year of meeting DSM-5 criteria for a severe alcohol, tobacco, or other drug use disorder (excluding caffeine)

• Have a first degree relative with schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I.

• Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin

• History of a medically significant suicide attempt

• Unwilling or unable to pause concurrent psychotherapy during the study.

Related Conditions & MeSH terms

• Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Drug:
• Psilocybin
The two psilocybin doses will be administered approximately 2 weeks apart in the form of an oral capsule. The first dose will be 25mg. For the second dosing session, participants will either remain on 25 mg of psilocybin, or will receive a dose of 40 mg, depending on the strength of subjective effects experienced during the first dosing session, as well as clinical judgment and participant preference.

Other:
• Trauma-focused psychotherapy
Components of trauma-focused psychotherapy will include Cognitive Processing Therapy and in vivo exposure. Such components of evidence-based psychotherapy may lower the safety risk profile for this vulnerable population and enhance the effect size and maintenance of psilocybin therapy.
• Standard psychological support
Standard psychological support involves providing a safe and emotionally supportive environment to participants throughout the course of their participation, and being attentive and responsive to their emotional needs. It includes continued review and discussion of experiences that participants encountered during the psilocybin sessions and the way that those experience relate to the participant's life and clinical status.

Locations

Country	Name	City	State
United States	Johns Hopkins Center for Psychedelic and Consciousness Research	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events	Adverse event monitoring throughout the study.	8 months
Primary	Columbia Suicide Severity Rating Scale (C-SSRS)	Used to assess severity of suicide ideation during every study visit. The C-SSRS has a score range of 0-5, with 0 being the least severe and 5 being the most severe. The scale has ten categories, all of which are binary responses (yes/no) that indicate the presence or absence of a behavior.	8 months
Primary	Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual (DSM)-5 (CAPS-5)	The CAPS-5 assessment consists of 30 items that are designed to measure the frequency and intensity of PTSD symptoms, covering all 20 DSM-5 PTSD symptoms. Each item is scored on a 5-point scale (0-4), with 0 being absent and 4 being extreme/incapacitating. Higher scores indicate higher severity of PTSD symptoms.	8 months
Primary	Ecological Momentary Assessment (EMA) of PTSD Checklist for DSM-5 (PCL-5)	The PTSD Checklist for DSM-5 (PCL-5; is a self-report psychometric instrument widely employed in both clinical and research settings to assess the presence and severity of PTSD symptoms as outlined in the DSM-5. The PCL-5's 20 items correspond to the DSM-5 symptom criteria for PTSD. For this study, PCL-5 symptoms are assessed using Ecological Momentary Assessment (EMA), such that respondents will be asked to rate the degree to which they have been bothered by each symptom within a preceding time-frame (e.g., preceding 2 hours, preceding day) on a Likert scale ranging from 0 (Not at all) to 4 (Extremely). A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items with higher scores indicating greater symptom severity.	3 months
Primary	World Health Organization Quality of Life Brief Version (WHOQOL-BREF)	An internationally recognized and validated tool for evaluating an individual's perception of their position in life, within the context of their culture and value system, and relative to their personal goals, expectations, standards, and concerns. Consists of multiple domains and facets, covering physical health, psychological health, social relationships, and environment. Each of these domains is assessed through several questions that the respondent answers on a five-point Likert scale. These scores are then used to compute an overall score, which is transformed linearly to a 0-100-scale with higher scores indicating a better perceived quality of life.	8 months
Secondary	Beck Depression Inventory II (BDI-II)	Used to assess depressive symptoms. BDI-II is scored by adding up the highest ratings for each of the 21 items on the questionnaire, which range from 0 to 3. The total score can range from 0 to 63, with higher scores indicating more severe depressive symptoms.	8 months
Secondary	Sheehan Disability Scale (SDS)	Used to assess functional impairment in three domains of disability that can be impaired during depression: work/school, social, and family life. Total score 0-30 (0 unimpaired, 30 highly impaired) Work/school (0-10) Social life (0-10) Family life/home responsibilities (0-10) Scores of =5 on any of the 3 scales; high scores are associated with significant functional impairment.	8 months
Secondary	Posttraumatic Maladaptive Beliefs Scale (PMBS)	This 15-item scale assesses maladaptive beliefs related to PTSD, indexed by three subscales including (1) Threat of Harm, (2) Self-Worth and Judgment, and (3) Reliability and Trustworthiness of Others. Scores on each subscale can be derived by summing items within each subscale. A list of subscale items and reverse-code directions are indicated on the measure. Possible scores range from 15-105, and subscale scores range from 5-35. Higher scores are indicative of more maladaptive beliefs in each of the three domains assessed within this measure.	3 months