Clinical trial NCT06407635: A Study of Psilocybin for PTSD
Official title: Psilocybin for PTSD With or Without Psychotherapy: A Pilot Study of Safety and Efficacy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Post Traumatic Stress Disorder
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Steven & Alexandra Cohen Foundation
name: Usona Institute
First posted: 2024-05-09
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

This study is supported in part by philanthropic contributions from private individuals. These donors are not involved in the design, conduct, or analysis of the research.

Eligibility criteria: Inclusion criteria:

* Be at least 21 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 (SSRI or SNRI) at a stable dose for at least 3 months.
* 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 alcohol, anxiolytics, stimulants, sedatives or hypnotics, opioids, dissociatives, cannabinoids, or other unapproved substances within 24 hours of psilocybin administration. Caffeine and nicotine are exceptions.
* Agree not to take any as needed (PRN) medications on the mornings of drug sessions
* Agree to stop taking 5HT2A antagonist medications at least 5 half-lives before psilocybin dosing.
* Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
* Have no classic psychedelic use in the past five years.
* Have at least a high school level of education or equivalent (e.g. GED).
* Weigh at least 40kg.
* (for female participants) Agree to use highly effective birth control measure within two weeks before and after dosing sessions.
* (for male participants) Agree to use contraception and refrain from sperm donation two weeks before and after 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 (QTc) interval (i.e., QTc \> 450 msec), artificial heart valve, or transient ischemic attack (TIA) in the past year
* Family history of Torsades de Pointes and sudden cardiac death
* 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)
* Current or history within one year of meeting DSM-5 criteria for Borderline Personality Disorder.
* 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.
* Determined to be at risk for re-exposure to the index trauma or other significant trauma in daily life.

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: 8 months
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: 8 months
measure: Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual (DSM)-5 (CAPS-5)
timeFrame: 8 months
measure: Ecological Momentary Assessment (EMA) of PTSD Checklist for DSM-5 (PCL-5)
timeFrame: 3 months
measure: World Health Organization Quality of Life Brief Version (WHOQOL-BREF)
timeFrame: 8 months
Secondary outcomes:
measure: Beck Depression Inventory II (BDI-II)
timeFrame: 8 months
measure: Sheehan Disability Scale (SDS)
timeFrame: 8 months
measure: Posttraumatic Maladaptive Beliefs Scale (PMBS)
timeFrame: 3 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Center for Psychedelic and Consciousness Research
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Sandeep Nayak, MD
role: PRINCIPAL_INVESTIGATOR
References: