Cannabis and Polysubstance Use: Response Inhibition and Stress Exposure

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this Phase I non-therapeutic trial is to examine the neurological effects of cannabis on stress reactivity and inhibition in healthy cannabis and stimulant co-users. It is expected for high ratio CBD:THC cannabis oil to have the largest effect and low ratio CBD:THC cannabis oil to have a moderate effect on outcome measures compared to placebo.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of British Columbia
• Treatments: Dronabinol

Criteria

Inclusion Criteria:

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

2. Have used cannabis via oral route of administration for non-medical purposes 8 out of the past 30 days, including:

1. Cannabidiol (CBD): on average, at least 50 milligrams (mg)

2. Delta-9-tetrahydrocannabinol (THC): on average, at least 10 mg

3. Have used stimulant drugs for non-medical purposes 5 out of the past 30 days, not including nicotine or caffeine. Stimulants include:

1. Cocaine, crack cocaine

2. Methylenedioxymethamphetamine (MDMA/ecstasy/molly)

3. Methamphetamine (meth, ice/crystal meth, speed)

4. Amphetamine (Adderall)

5. Amphetamine/dextroamphetamine (Adzenys XR-ODT, Dyanavel XR)

6. Amphetamine sulfate (Evekeo)

7. Dextroamphetamine (Dexedrine, ProCentra, Zenzedi)

8. Dexmethylphenidate (Focalin, Focalin XR)

9. Methylphenidate (Ritalin, Ritalin SR, Metadate ER, Methylin ER, Concerta, Daytrana, Jornay PM, Metadate CD, Quillivant XR, Quillichew ER, Ritalin LA)

10. Dextroamphetamine (Adderall XR)

11. Lisdexamfetamine (Vyvanse)

12. Mixed salts of a single-entity amphetamine product (Mydayis)

13. Serdexmethylphenidate/dexmethylphenidate (Azstarys)

4. For participants that are sexually active with the opposite sex (i.e., male-female sexual relationships), at least one of the following must apply:

a) For female participants: i) Use hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants) for at least 1 monthly cycle prior to drug administration session and for the duration of participation ii) Have an intrauterine device (IUD) or intrauterine system (IUS). For copper IUD at least for duration of study. For hormonal methods: for at least 7 days prior to participation and for duration of participation iii) Tubal ligation iv) Use double barrier methods of contraception for the duration of participation (i.e., simultaneous use of a physical barrier by each partner). Barrier methods of contraception can include: male condom female condom, cervical cap, diaphragm, contraceptive sponge. Use of spermicide alone is not considered a suitable barrier method for contraception.

b) For male participants: i) Have had a vasectomy prior to participation ii) Not trying to start a family

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

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

7. Are able to provide informed consent

8. Are able to complete assessments in English

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

10. Will provide proof of 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 start a family

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 had an adverse reaction (an unwanted and unexpected reaction), to less than 100mg of CBD and/or 25mg) 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 (e.g., blood pressure > 180mmHg/110mmHg), 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 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 had active delirium or recent delirium < 7 days within the past year, 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)

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

16. Respond "yes" to any items on the Mini International Neuropsychiatric Interview (M.I.N.I.) Screen Version 7.0.2

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

18. Have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)

19. Unable to attend sessions according to the study schedule

20. Unable to provide informed consent or complete assessments in English