The overall strategy is to recruit veterans with PTSD who report minimal current cannabis use but are interested in or considering therapeutic cannabis to manage mental health symptoms (anxiety, depression, PTSD and/or suicidality). The information gained from this study could lead to the development of new treatments for persons who suffer from post-traumatic stress disorder and maintain better mental health.

The total time commitment estimated per participant 20 study visits. This is broken down below:

Visit 1: Pre-Screening and informed Consent: During this visit the potential participant will learn about the study procedures and sign the informed consent documents. Also, during this visit a licensed clinician will administer the (CAPS-5).

Visit 2: Physical Examination and Questionnaires: During this visit the participant will undergo a full physical examination conducted by a licensed medical professional. At this time, they will collect blood, urine, breathalyzer and saliva samples.

Visit 3: Baseline Assessments & Pre-Treatment Behavioral Tasks and Neurocognitive Assessments: During this visit, we will administer a baseline assessment first, then we will administer behavioral tasks that measure reward decision-making. Pre-Treatment Fear Acquisition & Extinction Learning and Magnetic Resonance (MR) Scan: During this visit the participant will complete several computer tasks, and the study staff will be measuring reaction time and psychophysiological measures. The tasks that the participant will perform will show three different images and an aversive stimulus (e.g. which will be a mild electric shock to the ankle paired with a snake hissing sound of an animated snake) may follow one image most of the time, while the other images may never be followed by the aversive cue. The participant will need to try to predict whether the aversive cue will occur or not based on which image is shown and will be asked to repeatedly rate on a scale how likely it is that he or she thinks an aversive cue will occur after each image. Lastly, during the session the participant will also be asked to report his or her level of anxiety on a scale from 0 to 100.

Visit 4: Pre-Treatment Fear Extinction Recall with MR Scan: This visit will be very similar to Visit 4. Participants will participate in the same type of task inside the MR scanner, while the study staff measures reaction time and psychophysiological responding and brain activation. Participants will view the same images he or she did previously and may experience the same aversive stimulus as during Visit 3. Participants will again be asked to rate how much they expect to experience the aversive stimulus after each image and will also be asked to report their level of anxiety on a scale from 0 to 100.

Visit 5&6: Prolonged Exposure (PE) Sessions 1 & 2: These sessions will consist of psychoeducation that includes discussion or reactions to trauma, treatment rationale, breathing retraining, and review of the Subjective Units of Distress Scale (SUDS) to assess level of distress from 0 to 100 (100=extreme anxiety/distress) when facing fears. One session occurs weekly across 2 weeks.

Visit 7-10: These sessions will consist of repeated exposures to trauma memories (imaginal exposure) and avoided situations (in vivo exposure). As is standard, patients will also practice exposures (e.g., listen to tapes of imaginal exposure, carry out in vivo exposure) outside of PE sessions as "homework". At exposure-focused sessions (Sessions 3-6) either cannabis or placebo (PBO) will be administered just before the session. One session occurs weekly across 8 weeks.

Visit 11: This visit is similar as the previous just a little longer due to a mid-treatment assessment. (Session 7)

Visit 12-14: These sessions will consist of repeated exposures to trauma memories (imaginal exposure) and avoided situations (in vivo exposure). As is standard, patients will also practice exposures (e.g., listen to tapes of imaginal exposure, carry out in vivo exposure) outside of PE sessions as "homework". At exposure-focused sessions (Sessions 8-10) either cannabis or PBO will be administered just before the session. One session occurs weekly across 8 weeks.

Visit 15: Post-Treatment Assessments: PE Session 11 will include a review of therapeutic gains/relapse prevention/assessments.

Visit 16: Post-Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 3. Participants will participate in the same type of task inside the MR scanner, while the study staff measures reaction time and psychophysiological responding and brain activation. Participants will view the same images he or she did previously and may experience the same aversive stimulus as during Visit 3. Participants will again be asked to rate how much they expect to experience the aversive stimulus after each image and will also be asked to report their level of anxiety on a scale from 0 to 100.

Visit 17: Post- Treatment Behavioral Tests and MR Scan: This visit will be very similar to Visit 4. Participants will participate in the same type of task inside the MR scanner, while the study staff measures reaction time and psychophysiological responding and brain activation. Participants will view the same images he or she did previously and may experience the same aversive stimulus as during Visit 5. Participants will again be asked to rate how much they expect to experience the aversive stimulus after each image and will also be asked to report their level of anxiety on a scale from 0 to 100.

Visit 18: 3-Month Follow-Up Treatment Assessment: This session is similar to Visit 15 and will include review of therapeutic gains/relapse prevention/assessments.

Visit 19: 6-Month Follow-Up Treatment Assessment: This session is similar to Visit 18 and will include review of therapeutic gains/relapse prevention/assessments.

Visit 20: 9-Month Follow-Up Treatment Assessment: This session is similar to Visit 19 and will include review of therapeutic gains/relapse prevention/assessments.

Inclusion Criteria:

• Willing and able to consent to the study
• Agree to comply with requirements and procedures
• Veteran who has served in a branch of the US armed forces
• Between ages 18-60
• Report using cannabis within the past three years but not more than twice in the past month
• Exposure to Criterion A stressor defined by CAPS-5 and identified by Life Events Checklist-5 (LEC-5); trauma does not have to be related to combat or military service
• Significant PTSD severity as indicated by CAPS-5 diagnosis and/or score >= 25 of at least one month prior to study entry, PTSD is patient's primary concern
• not currently receiving any psychotherapy for PTSD

Exclusion Criteria:

• Pregnant, lactating or are a heterosexually active, pre-menopausal woman who is NOT using medically approved birth control (e.g., oral or depot contraception, contraceptive implant, IUD, condom/foam, sterilization, tubal ligation)
• Current or past diagnosis of any bipolar or related disorder or schizophrenia spectrum and other psychotic disorder as determined by the SCID-5 or previous diagnosis by a licensed psychologist or psychiatrist
• Determined to be at high risk for suicide requiring immediate intervention based on the C-SSRS and/or clinician judgment
• Meet criteria for substance use disorder other than Cannabis Use Disorder or Alcohol (Mild or Moderate) or Nicotine Use Disorder, determined by the SCID-5
• Presence of contraindications, current or past allergic or adverse reaction, or known sensitivity to smoking cannabis
• Concomitant treatment with medication taken daily that has level 1 evidence indicating severe drug-drug interactions with cannabis
• Currently receiving psychotherapy for PTSD or previously received exposure-based PTSD treatment
• Current diagnosis or evidence of significant or uncontrolled hematological, endocrine, cerebrovascular, cardiovascular, systemic, pulmonary, pulmonary fibrosis, or other forms of restrictive lung disease, immunocompromising, or neurological disease
• Current diagnosis of a mood, anxiety, or other disorder that is more clinically salient than PTSD
• Cognitive exhibit impairment
• Lack of fluency in English
• Insufficient memory of the index traumatic event
• Pervasive development disorder history
• Seeking or currently undergoing treatment for Cannabis Use Disorder.
• Traumatic brain injury (TBI) with current cognitive impairment related to TBI
• Exclusively left-handed (score of -100 on Handedness Questionnaire)
• claustrophobic
• MRI contraindications (e.g., ferrous metal in head/body)