Cannabis and Polysubstance Use: Response Inhibition and Stress Exposure

Inclusion criteria:

1. Are 19-35 years old at the start of the study

2. Have used oral cannabis, including at least 5mg of THC, at least once in their life

3. Have used cannabis at least once in the past year

4. Used cannabis less than 3 times per week on average, in the past 3 months

5. Are using an effective and/or highly effective method of contraception and willcontinue to do so for the duration of participation in the study. Health Canada'sdefinition of effective methods of contraception include barrier methods ofcontraception (e.g. male condom, female condom, cervical cap, diaphragm,contraceptive sponge). Health Canada's definition of highly effective methods ofcontraception includes hormonal contraceptives (e.g. combined oral contraceptives,patch, vaginal ring, injectables, and implants); intrauterine device (IUD) orintrauterine system (IUS); vasectomy and tubal ligation.

6. Females: are not undergoing alternative fertility methods, such as IVF, or otherwisetrying to start a family for the duration of participation

7. Males: will not be donating sperm at some point during the duration of participation

8. Are able to provide informed consent

9. Are able to complete assessments in English

10. Are able to attend sessions according to the study schedule

11. Will provide proof of 2 doses of an approved COVID-19 vaccination

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 (anunwanted 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 cannabiswithin last 6 months

7. Have a major physical problem/health concern, including:

8. Liver-cirrhosis or other liver disease

9. Diabetes

10. Chronic illness that may increase risk for adverse reactions to cannabis

11. Chronic pain

12. Genetic glucuronidation disorders (e.g., Gilbert's disease)

13. Cardiovascular disease, including ischemic heart disease with unstable anginaor recent acute coronary syndrome in the last 3 months, uncontrolledarrhythmias, poorly controlled hypertension or high blood pressure (e.g., 130/80), or severe heart failure

14. Delirium: active delirium or recent delirium < 7 days, or at significant riskof delirium due to multiple comorbidities (e.g., very elderly, cognitiveimpairment, cerebrovascular disease) and contributing drugs (e.g., alcohol,stimulants, high doses of benzodiazepines, opioid, sedatives, psychoactivemedications)

15. Are taking any of the following medications:

16. Any medication that impacts the central nervous system, brain, and/or metabolicsystem

17. Psychotropic medications, sedatives, and central nervous system depressants,including sleeping pills, tranquilizers, some pain medications, some allergyand cold medications, and anti-seizure medications

18. Medications otherwise affecting the central nervous system, includingamphetamines and other sympathomimetics

19. Allergy medications (antihistamines; within 24 hours)

20. Heart medications

21. Blood pressure medication

22. Steroid medications

23. Opioids or other pain medications

24. Anticholinergics: drugs that block acetylcholine, a chemical signal that playsa role in memory and learning.

25. Drugs metabolized by cytochrome P450 enzymes, including amitriptyline,fentanyl, sufentanil, and alfentanil

26. Highly protein-bound drugs, including warfarin, cyclosporine, and amphtericin

27. Drugs metabolized by UGT enzymes, including propofol, antivirals

28. Antiretroviral drugs

29. Stomach acid inhibitors

30. Antibiotics and antifungal medications

31. Heart medications

32. Other medications/substances interfering with CYP2C19 receptors i. Inhibitors: Fluvoxamine, isoniazid (INH), ritonavir ii. Inducers: Carbamazepine,phenytoin, rifampin iii. Substrates: Omeprazole (Prilosec), phenobarbital, phenytoinr. 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, Hypericumperforatum (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)

33. 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, electricalstimulator, and/or ear or eye implant) including retained wires that has beenremoved (e.g., pacemaker wires not attached to a pacemaker) ii. Stainless steelintrauterine 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, orother 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 anyblood vessel xiii. Surgery, medical procedure or tattoos (including tattooedeyeliner) in the last six weeks xiv. Other metallic prostheses b. Have a personal orfamily history of seizures c. Have any significant neurological disorder including,but not limited to: i. Any condition likely to be associated with increasedintracranial pressure ii. Space-occupying brain lesion iii. Seizure iv. Cerebralaneurysm v. Parkinson's disease vi. Huntington's chorea vii. Multiple sclerosisviii. Significant head trauma with loss of consciousness for greater than or equalto 5 minutes d. Claustrophobia (i.e., feel uncomfortable in small spaces) or fear ofloud, repetitive sounds, or inability to lay still. Participants will have to liestill in the confined space of the MRI scanner.

34. Work nightshifts

35. Have any diagnosed sleep disorders

36. Have dyscalculia

37. Have a neurodevelopmental disorder or cognitive impairments, including:

38. Autism Spectrum Disorder

39. Attention Deficit/Hyperactivity Disorder (ADHD)

40. Have schizophrenia spectrum disorder and/or history of psychosis

41. Meet criteria for potential mental health disorder in the Mini InternationalNeuropsychiatric Interview (M.I.N.I.) Screen Version 7.0.2, except for alcohol andcannabis use disorders

42. Any diagnosed current mental health disorder and/or diagnosis of a mental healthdisorder within the past year

43. Have a non-correctable clinically significant sensory impairment (e.g., cannot hearwell 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