Cannabis Effects on Antiretroviral Therapy Pharmacokinetics and Neurotoxicity
- Conditions
- Cannabis UseHIV
- Interventions
- Registration Number
- NCT04800159
- Lead Sponsor
- University of California, San Diego
- Brief 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.
- Detailed Description
People with human immunodeficiency virus (HIV) commonly use cannabis but whether cannabis affects the antiretroviral therapy (ART) that treats HIV is not well known. Cannabis can inhibit the activity of enzymes that metabolize and eliminate ART drugs from the body, which could result in higher concentrations of ART drugs in the body. Cannabis may also affect the distribution of ART drugs into the brain, which could have both beneficial (e.g., better HIV control) and detrimental (e.g., toxicity) effects. The effects of cannabis may are likely influenced by factors like how much is used (e.g., light vs. heavy use) and the route of use (e.g., smoked vs. ingested). This study will address whether cannabis affects ART concentrations in blood and cerebrospinal fluid as well as mood, and thinking. The project will have two phases. Phase 1 is an observational study, in which 120 people will be assessed once 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description CBD Cannabis CBD Cannabis 0.35% THC/ 11.27% CBD THC Cannabis THC Cannabis 11.86% THC/ 1.12% CBD Placebo Placebo ≤ 0.01% THC/ ≤ 0.01% CBD
- Primary Outcome Measures
Name Time Method 1b iii. Comparison between the effects of placebo and THC on ART pharmacokinetics and between the effects of placebo and CBD on ART pharmacokinetics 3 to 11 days Comparison of the the area under the time-concentration curve of ART pharmacokinetics for placebo and THC and placebo and CBD (n=40). The effect size will be measured as the standardized difference in mean outcomes between any two groups (Cohen's d).
1a iii. Change in ART drug concentrations in blood 2 hours; measured before ART ingestion and at 2 hours after the ART ingestion This will be done separately for CYP and UGT groups (estimated N=60 in each).
3a. ii. Correlation between HIV DNA and ART drug concentration. Up to 5 weeks: baseline to administration visits Multivariable logistic regressions will be used for testing correlation between HIV DNA and ART drug concentration (N=60 in each UGT and CYP groups).
3b ii. Effects of cannabis use on the correlation between ART and depression. 3 to 11 days Depression (measured with the Beck Depression Inventory-II) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
3b v. Effects of cannabis use on the correlation between ART and emotional health. 3 to 11 days The National Institutes of Health Toolbox-Emotional Battery outcome, Psychological Wellbeing, will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. This measure ranges between 0 and 100 with lower values reflecting worse Psychological Wellbeing.
1b i. Effects of placebo, THC, and CBD on ART drug concentration 5 hours The investigators will use a mixed effects model to assess effects of acute cannabis treatment (placebo, THC, or CBD: N=40) on the area under the time-drug concentration curve.
1b iv. Comparison between the effects of placebo and CBD on the CSF/plasma ratio of ART drug concentrations and between the effects of placebo and THC on the CSF/plasma ratio of ART drug concentrations 3 to 11 days Comparison of the the CSF/plasma ratio of ART drug concentrations with placebo and CBD and with placebo and THC (n=40). The effect size will be measured as the standardized difference in mean outcomes between any two groups (Cohen's d).
2b. Examine the correlation between ART concentration in CSF and blood during placebo treatment compared to THC and CBD administration. 3 to 11 days The investigators will use a mixed effects model to evaluate the effects of cannabis on the correlation between ART concentration in CSF and blood (n = 40).
1a i. Antiretroviral therapy (ART) drug concentration in blood Cross-sectional; measured before ART ingestion This will be done separately for participants who use ART drugs that are predominantly metabolized by cytochrome P450 (CYP) or uridine 5'-diphospho-glucuronosyltransferase (UGT) (estimated N=60 in each).
1a ii. Cerebrospinal fluid (CSF)/plasma ratio of ART drug concentrations Cross-sectional; measured before ART ingestion This will be done separately for CYP and UGT groups (estimated N=60 in each).
1a iv. Change in CSF/plasma ratio of ART drug concentrations 2 hours; measured before ART ingestion and at 2 hours after the ART ingestion This will be done separately for CYP and UGT groups (estimated N=60 in each).
1b ii. Effects of placebo, THC and CBD on the CSF/plasma ratio of ART drug concentrations 5 hours The investigators will use a mixed effects model to assess effects of acute cannabis treatment (placebo, THC, or CBD: N=40) on CSF/plasma ratio of ART drug concentrations
2a. Effects of chronic cannabis use on the CSF/serum albumin ratio and P-glycoprotein (P-gp) expression. 3 to 11 days Multivariate linear regression will be used to regress markers of blood-brain barrier integrity and P-gp on cannabis use (n = 120), then ART drug concentrations on blood-brain barrier integrity and P-gp separately for the UGT and CYP groups
2c. Effects of THC or CBD on uridine 5'-diphospho-glucuronosyltransferase (UGT) activity compared to placebo. 3 to 11 days The investigators will use a mixed effects model to examine the effects of drug treatment on UGT metabolism (n = 40).
3b iii. Effects of cannabis use on the correlation between ART and emotional health. 3 to 11 days The National Institutes of Health Toolbox-Emotional Battery outcome, Negative Affect, will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. This measure ranges between 0 and 100 with higher values reflecting more Negative Affect.
3b iv. Effects of cannabis use on the correlation between ART and emotional health. 3 to 11 days The National Institutes of Health Toolbox-Emotional Battery outcome, Social Satisfaction, will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. This measure ranges between 0 and 100 with lower values reflecting worse Social Satisfaction.
3b vi. Effects of cannabis use on the correlation between ART and neurotoxicity. 3 to 11 days A measure of neurotoxicity (mitochondrial DNA) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
3a. i. Correlation between CD4+ T-cell count and ART drug concentration. Up to 5 weeks: baseline to administration visits Multivariable linear regressions will be used for testing correlation between CD4+ T-cell count and ART drug concentration (N=60 in each UGT and CYP groups).
3b i. Effects of cannabis use on the correlation between ART and neurocognitive performance. 3 to 11 days The total cognitive outcome from the National Institutes of Health Toolbox will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. Values range from 0 to 100 with lower values being worse.
3b vii. Effects of cannabis use on the correlation between ART and neurotoxicity. 3 to 11 days A measure of neurotoxicity (8-hydroxydeoxyguanosine) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
3b viii. Effects of cannabis use on the correlation between ART and neurotoxicity. 3 to 11 days A measure of neurotoxicity (F2-isoprostane) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
- Secondary Outcome Measures
Name Time Method 1b vi. Comparison between the effects of THC and CBD on the CSF/plasma ratio of ART drug concentrations. 3 to 11 days Comparison of treatment arm to the CSF/plasma ratio of ART drug concentrations.
1b v. Comparison between the effects of THC and CBD on ART pharmacokinetics. 3 to 11 days Comparison of the treatment arm to the the area under the time-concentration curve of ART pharmacokinetics (n=40).
Trial Locations
- Locations (1)
Ucsd Hnrp-Cmcr
🇺🇸San Diego, California, United States