Group Psilocybin-Assisted Therapy for Post-Traumatic Stress Disorder

This study is a community-informed, pragmatic, open-label, phase 1 clinical trial of group-format psilocybin-assisted therapy (GPAT) for individuals with post-traumatic stress disorder (PTSD). The primary objectives of this phase 1 study are to assess the safety and feasibility of (GPAT) for individuals with (PTSD) and to evaluate preliminary effects on PTSD severity.

These will be assessed by the following outcome measures:

• Proportion of participants completing the study protocol
• Incidence of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Mean change in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD checklist for DSM-5 (PCL-5). The CAPS-5 and PCL-5 are based on the DSM-5 not the DSM-5-TR.

Inclusion criteria

General:

-T+H years of age and <89 years of age

Identify as a member of one of the cohorts to be studied:

• Veteran or first responder
• Female survivor of sexual violence
• Indigenous person
• Not pregnant, planning to become pregnant, or breastfeeding; if able to become pregnant, willing to use reliable form of birth control for the duration of the study
• If needed, ability and willingness to taper and discontinue medications that may interfere with the action of psilocybin
• Ability to read, speak, and understand English
• Ability and willingness to consent to the terms of the study, including attending all trial visits (most of which will occur in a group setting), preparation and
• follow-up sessions, and completing all trial evaluations
• Ability and willingness to swallow capsules

PTSD severity:

• Meet criteria for PTSD, as defined in the DSM-5
• At screening, symptoms of moderate to severe PTSD (PCL-5 score of 34 or greater) present for at least six months

Exclusion criteria

• Inability to achieve five days of abstinence from alcohol, non-prescribed opioids, methamphetamines, cocaine, benzodiazepines, or other illicit substances
• Inability or unwillingness to remain abstinent from cannabis use for 24 hours prior to psilocybin dosing session and 12 hours after receiving the dose of psilocybin
• Risk for clinically significant acute withdrawal from any substance that would cause safety concern on the day of dosing
• Any medical condition that would preclude safe participation in the study, including the following, as determined by medical history review, physical examination, electrocardiogram (ECG), and clinical laboratory tests: Pregnancy/breastfeeding

Cardiovascular conditions:

• Uncontrolled hypertension, defined as >140/90 mm Hg at screening or baseline or >145/95 mm Hg on presentation for dosing day assessed on three consecutive blood pressure measurements
• History of myocardial infarction, cardiac ischemia, congestive heart failure, clinically relevant valvular heart disease, or pulmonary hypertension; any other significant history of cardiovascular condition, based on the clinical judgment of the Trial Physician, which would make a participant unsuitable for the trial
• ECG: Clinically significant abnormality (e.g. atrial fibrillation based on judgement of trial physician including prolonged corrected QT interval (QTc> 450 milliseconds (males) or >470 milliseconds (females)
• Poorly controlled diabetes (HbA1c >8.0%; clinically significant hypoglycemia in the past 6 months)
• Neurological conditions (e.g. epilepsy or other seizure disorder) or neurodegenerative disease (e.g., dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis.), or brain tumor that would impact participation in the trial Serious abnormalities of complete blood count or chemistry

• Severe hepatic impairment
• Severe renal impairment,
• Unstable existing thyroid disorder
• Any of the following psychiatric conditions:

• Active suicidal ideation; history of hospitalization for suicide attempt within the 12 months prior to screening, affirmative responses to C-SSRS questions 4 or 5
• Confirmed diagnosis of schizophrenia or other psychotic disorder, firstdegree relative with schizophrenia
• Axis-II diagnosis
• Use of psychedelics (e.g., psilocybin, mescaline, ayahuasca, DMT, LSD, MDMA, or ketamine) resulting in a discrete psychedelic experience in the past six months.

Using daily dose of psilocybin mushrooms at dose <0.2 mg or LSD at <20 mcg per day for <30 days in a year ("microdosing") will not be an exclusion criterion.

However, participants must agree to no further use of psychedelics during this study starting at screening.

• Returning to an unsafe environment and/or inadequate social support-Any other condition, physical or psychological symptom, medication, or other relevant finding prior to randomization that, based on the clinical judgment of trial personnel, would make a participant unsuitable for the trial.-
• Participation in experimental treatment for PTSD or any research studies within 30 days of screening assessment