Clinical trial NCT05562973: Safety and Tolerability of Psilocybin in Post-Traumatic Stress Disorder
Official title: Safety and Tolerability of Psilocybin in Post-Traumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Post-Traumatic Stress Disorder
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2022-10-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Peak Post-Administration Blood Pressure
timeFrame: Approximately 1.5 - 2 months
measure: Mean Peak Post-Administration Heart Rate
timeFrame: Approximately 1.5 - 2 months
measure: Mean Pre-Administration Suicide Ideation Scores (Columbia Suicide Severity Rating Scale - Severity Factor)
timeFrame: Approximately 3 weeks
measure: Mean Change in Suicide Ideation Scores (Columbia Suicide Severity Rating Scale - Severity Factor)
timeFrame: Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration
Secondary outcomes:
measure: Mean Change in Clinician-Administered PTSD Scale for DSM-5 scores
timeFrame: Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration
measure: Mean Change in PTSD Checklist Scores
timeFrame: Approximately 3 weeks pre-administration; approximately 1.5 - 2 months post-administration
Other outcomes:
Locations:
Study officials:
affiliation: Johns Hopkins University
name: Matthew W Johnson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.