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 for non-medical purposes twice the past month (30 days)
3. Have previously used a minimum of 20mg of CBD
4. Have previously used a minimum of 5mg THC
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, contraceptivesponge). Health Canada's definition of highly effective methods of contraceptionincludes hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginalring, injectables, and implants); intrauterine device (IUD) or intrauterine 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 angina orrecent acute coronary syndrome in the last 3 months, uncontrolled arrhythmias,poorly controlled hypertension or high blood pressure (e.g., 130/80), or severeheart failure
14. Delirium: active delirium or recent delirium < 7 days, or at significant risk ofdelirium due to multiple comorbidities (e.g., very elderly, cognitive impairment,cerebrovascular disease) and contributing drugs (e.g., alcohol, stimulants, highdoses of benzodiazepines, opioid, sedatives, psychoactive medications)
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 allergy andcold 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 plays arole 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 been removed (e.g., pacemaker wires not attached to a pacemaker) ii. Stainless steel intrauterinedevice (IUD) iii. Metal in eye or orbit, or metal slivers iv. Ferromagnetic aneurysmclip 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 sixweeks xiv. Other metallic prostheses b. Have a personal or family history of seizuresc. Have any significant neurological disorder including, but not limited to: i. Anycondition likely to be associated with increased intracranial pressure ii.Space-occupying brain lesion iii. Seizure iv. Cerebral aneurysm v. Parkinson's diseasevi. Huntington's chorea vii. Multiple sclerosis viii. Significant head trauma withloss 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 inabilityto lay still. Participants will have to lie still in the confined space of the MRIscanner.
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 opiatesmore than twice in the past 30 days