Inhaled Cannabis for Treatment of PTSD

Inclusion criteria

• Be at least 18 years old.
• Be a veteran with PTSD lasting 6 months in duration.
• Meet DSM-5 criteria for PTSD with symptoms (as assessed by the MINI).
• Have PTSD of at least moderate severity (PCL-5 score of 33 or more) at the time of screening.
• For participants assigned female sex at birth:

a) A participant is eligible to participate if not pregnant, and one of the following conditions applies: i) Is not able to become pregnant as defined in protocol (Appendix 2) OR ii) Is a person able to be pregnant (PABP) and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in the protocol (Appendix 2) during the study intervention period and for at least 14 days after the Study Termination visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.

b) A PABP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at Screening, Introductory Session 1, Resupply, and EoT visits c) The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy.

• Be stable on any pre-study medications and/or psychotherapy prior to study entry, agree to inform physician(s)/clinician(s) providing current care about participation in the study, and agree to report any changes in medication or psychotherapy treatment regimen during the study-to-study staff.
• Have previously inhaled cannabis (e.g. smoked or vaporized cannabis).
• Be willing to commit to medication dosing and delivery method, to complete evaluation instruments, and attend all study visits.
• Agree to use only cannabis provided by site staff and agree to required follow up periods for the duration of the study.
• Agree to keep all cannabis provided by site staff securely stored in the provided lock box and not to share/distribute cannabis to any other individual.
• Be proficient in reading and writing in English and able to effectively communicate with site staff.
• Agree not to participate in any other interventional clinical trials during the study.
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
• Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
• Must be able and willing to record information digitally on a personal device (phone or computer) with internet access.

Exclusion criteria

• Are pregnant, nursing, or are a person able to become pregnant who are not practicing an effective means of birth control.
• Have current major depressive disorder with primary psychotic features assessed via the Mini-International Neuropsychiatric Interview (MINI).
• Have current or past DSM-5 diagnosis of eating disorder with active purging, personality disorders, primary psychotic disorder, or bipolar affective disorder type 1 (as assessed with the MINI and the SCID-5-PD).
• Have current or past DSM-5 diagnosis of dissociative identity disorder, positive family history (first degree relative) of psychotic disorder or bipolar affective disorder type 1 (as assessed by medical history review).
• Are at high risk of suicide attempt: any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to Columbia Suicide Severity Rating Scale (C-SSRS), and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled. Any participant presenting the following on the Baseline/Screening C-SSRS will be excluded:

• Suicidal ideation score of 4 or greater within the last month of the assessment at a frequency of once a week or more.
• Suicidal ideation score of 5 within the last 6 months of the assessment.
• Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months. Participants with non-suicidal self- injurious behavior may be included if approved by the Medical Monitor.
• Would present serious risk to others as established by clinical interview and contact with treating psychiatrist.
• Have a current moderate (meets 5 of 11 diagnostic criteria per DSM-5) or severe (meets at least 6 of 11 diagnostic criteria per DSM-5) alcohol or cannabis use disorder within the 12 months prior to enrollment. Participants with a substance use disorder other than alcohol or cannabis are excluded.
• Have a positive urine drug screen for opiates, methamphetamine, cocaine, THC, and amphetamines (unless prescribed). Participants with a positive THC urine analysis tests are excluded from the study but will be allowed to rescreen (maximum twice) after a 1-month cessation of cannabis use.
• Have a history of arrhythmia, other than occasional premature atrial contractions (PACs) and PVCs in the absence of ischemic heart disease, within 12 months of screening.

• Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled only if they have been successfully treated with ablation and have not had recurrent arrhythmia for at least one year off all antiarrhythmic drugs, or are under adequate and stable pharmacologic treatment for atrial fibrillation for at least a year, as confirmed by a cardiologist.
• Have a current or history of chronic obstructive pulmonary disease or asthma.
• Have a current diagnosis or evidence of significant or uncontrolled hematological, endocrine, cerebrovascular, cardiovascular, coronary, pulmonary, gastrointestinal, renal, hepatic, immunocompromising, or neurological disease according to CI's discretion.
• Have any current problem, which in the opinion of the CI or Medical Monitor, might interfere with participation.
• Have any known allergies to cannabis or contraindication for inhalation of cannabis.
• Are not able to give adequate informed consent.
• Are not able to attend required face-to-face visits or those who plan to move out of the area within the treatment period.