Cannabis and Polysubstance Use: Response Inhibition and Stress Exposure

Exclusion criteria

• 1. Are left-handed or ambidextrous 2. Females: are pregnant, nursing, or not on safe pregnancy protection 3. Are trying to conceive 4. Have a known or suspected allergy to cannabinoids and/or palm/coconut oil 5. Are hypersensitive to CBD and/or THC and/or have ever had an adverse reaction (an unwanted and unexpected reaction), to less than 40mg of CBD and/or 10mg THC 6. Have had an adverse reaction (unwanted, unexpected reaction or symptoms) to cannabis within last 6 months 7. Have a major physical problem/health concern, including: 1. Liver-cirrhosis or other liver disease 2. Diabetes 3. Chronic illness that may increase risk for adverse reactions to cannabis 4. Chronic pain 5. Genetic glucuronidation disorders (e.g., Gilbert's disease) 6. Cardiovascular disease, including ischemic heart disease with unstable angina or recent acute coronary syndrome in the last 3 months, uncontrolled arrhythmias, poorly controlled hypertension or high blood pressure (e.g., 130/80), or severe heart failure 7. Delirium: active delirium or recent delirium \< 7 days, or at significant risk of delirium due to multiple comorbidities (e.g., very elderly, cognitive impairment, cerebrovascular disease) and contributing drugs (e.g., alcohol, stimulants, high doses of benzodiazepines, opioid, sedatives, psychoactive medications) 8. Are taking any of the following medications: 1. Any medication that impacts the central nervous system, brain, and/or metabolic system 2. Psychotropic medications, sedatives, and central nervous system depressants, including sleeping pills, tranquilizers, some pain medications, some allergy and cold medications, and anti-seizure medications 3. Medications otherwise affecting the central nervous system, including amphetamines and other sympathomimetics 4. Allergy medications (antihistamines; within 24 hours) 5. Heart medications 6. Blood pressure medication 7. Steroid medications 8. Opioids or other pain medications 9. Anticholinergics: drugs that block acetylcholine, a chemical signal that plays a role in memory and learning. 10. Drugs metabolized by cytochrome P450 enzymes, including amitriptyline, fentanyl, sufentanil, and alfentanil 11. Highly protein-bound drugs, including warfarin, cyclosporine, and amphtericin 12. Drugs metabolized by UGT enzymes, including propofol, antivirals 13. Antiretroviral drugs 14. Stomach acid inhibitors 15. Antibiotics and antifungal medications 16. Heart medications 17. Other medications/substances interfering with CYP2C19 receptors i. Inhibitors: Fluvoxamine, isoniazid (INH), ritonavir ii. Inducers: Carbamazepine, phenytoin, rifampin iii. Substrates: Omeprazole (Prilosec), phenobarbital, phenytoin r. Other medications/substances interfering with CYP3A4 receptors: i. Inhibitors: Clarithromycin (Biaxin), diltiazem (Cardizem), erythromycin, grapefruit juice, itraconazole (Sporanox), ketoconazole (Nizoral), nefazodone (Serzone), ritonavir, telithromycin (Ketek), verapamil (Calan) ii. Inducers: Carbamazepine, Hypericum perforatum (St. John's wort), phenobarbital, phenytoin, rifampin iii. Substrates: Alprazolam (Xanax), amlodipine (Norvasc), atorvastatin (Lipitor), cyclosporine (Sandimmune), diazepam (Valium), estradiol (Estrace), simvastatin (Zocor), sildenafil (Viagra), verapamil, zolpidem (Ambien) 9. Other MRI contraindications (conditions that make MRI procedure inadvisable): a. Have implanted metal clips or wires, including: i. Implanted electronic device (e.g., pacemaker, defibrillator implanted medication infusion pump, electrical stimulator, and/or ear or eye implant) including retained wires that has been removed (e.g., pacemaker wires not attached to a pacemaker) ii. Stainless steel intrauterine device (IUD) iii. Metal in eye or orbit, or metal slivers iv. Ferromagnetic aneurysm clip v. Coil, catheter, or filter in any blood vessel vi. Orthopedic hardware (artificial joint, plate, screw, rod) vii. Shrapnel, bullets, or other metal fragments (i.e., metal in eye or orbit) viii. Artificial heart valve ix. Ear or eye implant x. Brain aneurysm clip xi. Implanted electronic device (i.e., drug infusion pump, electrical stimulator) xii. Coil, catheter, or filter in any blood vessel xiii. Surgery, medical procedure or tattoos (including tattooed eyeliner) in the last six weeks xiv. Other metallic prostheses b. Have a personal or family history of seizures c. Have any significant neurological disorder including, but not limited to: i. Any condition likely to be associated with increased intracranial pressure ii. Space-occupying brain lesion iii. Seizure iv. Cerebral aneurysm v. Parkinson's disease vi. Huntington's chorea vii. Multiple sclerosis viii. Significant head trauma with loss of consciousness for greater than or equal to 5 minutes d. Claustrophobia (i.e., feel uncomfortable in small spaces) or fear of loud, repetitive sounds, or inability to lay still. Participants will have to lie still in the confined space of the MRI scanner. 10. Work nightshifts 11. Have any diagnosed sleep disorders 12. Have dyscalculia 13. Have a neurodevelopmental disorder or cognitive impairments, including: 1. Autism Spectrum Disorder 2. Attention Deficit/Hyperactivity Disorder (ADHD) 14. Have schizophrenia spectrum disorder and/or history of psychosis 15. Meet criteria for potential mental health disorder in the Mini International Neuropsychiatric Interview (M.I.N.I.) Screen Version 7.0.2, except for alcohol and cannabis use disorders 16. Any diagnosed current mental health disorder and/or diagnosis of a mental health disorder within the past year 17. Have a non-correctable clinically significant sensory impairment (e.g., cannot hear well enough to cooperate with interview) 19\) Are unable to attend sessions according to the study schedule 20) Have used opiates more than twice in the past 30 days