Cannabis Effects on Antiretroviral Therapy Pharmacokinetics and Neurotoxicity

• Status: Recruiting
• Trial end date: 2025-04-30
• Target enrollment: 0
• Participant gender: All

Summary

This study will address whether cannabis affects antiretroviral therapy (ART) drug concentrations, mood, and thinking. The project will have two phases. Phase 1 is an observational study, in which 120 people will be assessed to evaluate the effects of chronic cannabis use on ART drug concentrations, mood, and thinking. In Phase 2, the study will administer cannabis (or placebo) to 40 people to examine its acute effects on ART drug concentrations.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of California, San Diego
• Collaborator: Center for Medicinal Cannabis Research

Criteria

Inclusion Criteria for All Visits:

1. Age 18 or older;

2. Capacity to provide informed consent;

3. Presence of HIV infection by a standard diagnostic test;

4. On a stable ART regimen for at least 3 months;

5. Taking an ART drug that is metabolized by either cytochrome p450 (CYP) isozymes or by uridine 5'-diphospho-glucuronosyltransferase (UGT) isozymes; and

6. Willing to abstain from cannabis for at least 24 hours prior to the Phase 1 assessment.

Additional Inclusion Criteria for participation in Phase 2 (interventional):

1. Treatment with dolutegravir;

2. Use of cannabis in the past two years without a severe adverse reaction (e.g., disorientation, paranoia, or hallucinations). The two-year cutoff is to ensure exposure to modern cannabis, which is more likely to match the drug concentrations administered in this study;

3. Willing to refrain from driving or operating heavy machinery after the visit; and

4. Willing to abstain from cannabis for at least 48 hours prior to the cannabis administration visits.

Exclusion Criteria for All Visits:

1. Traumatic brain injury, including head injury with loss of consciousness for greater than 30 minutes or resulting in neurologic complications;

2. Dementia, including Alzheimer's disease;

3. History of stroke with residual neurologic sequelae;

4. History of seizure disorder with a seizure in the past year;

5. Severe psychiatric disorder (e.g., schizophrenia) that might make the person's participation in the study unsafe;

6. Substance or alcohol use disorder in the past 12 months;

7. Contraindications to lumbar puncture for those consenting to lumbar puncture (e.g., coagulopathy).

Additional Exclusion Criteria for participation in the cannabis administration visits:

1. Younger than 21 years (due to safety of cannabis in children and adolescents);

2. Respiratory condition that would be exacerbated by inhaling vaporized cannabis (e.g., asthma or chronic obstructive pulmonary disease) or limited lung capacity that would prevent the individual from performing the Foltin puff procedure;

3. History of cardiovascular disease, including myocardial infarction;

4. Uncontrolled hypertension with systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure greater than 100 mm Hg prior to study product administration;

5. Resting pulse greater than 100 beats per minute prior to study product administration;

6. Pregnancy as determined by a human chorionic gonadotropin urine test, women who are lactating, or unwillingness to prevent pregnancy during the cannabis administration portion of the study (using birth control in women of child-bearing age). Acceptable methods of birth control are: oral contraceptive pills, diaphragm, condom, progestin implant, intrauterine contraceptive device, sterilization, etc;

7. Active opportunistic infection or malignancy requiring treatment;

8. CD4+ T-cell count less than 200 cells/µL;

9. Estimated glomerular filtration rate < 40 mL/minute, indicative of renal dysfunction;

10. Hepatic transaminases > 2 times the upper limit of normal;

11. Current severe depressive symptoms (BDI-II score ≥ 31) or suicidal ideation;

12. Known sensitivity to acetaminophen (the probe for UGT activity);

13. Current use of substances that could have adverse interactions with acetaminophen or cannabis (e.g., grapefruit juice).