Effects of Cannabidiol and Tetrahydrocannabinol on Microbiome and Neuroinflammation in HIV

• Aged 21 to 70 years old
• Possess the capacity to provide informed consent to a set of neuromedical assessment procedures.
• Experience with cannabis use at least once in the past 5 years without major adverse effects (e.g., psychosis, syncope)
• No or low cannabis use in the past 2 weeks, defined as no cannabis exposure or use or use limited to only once in the past 2 weeks.
• Willing to abstain from use of cannabis, CBD, THC, or synthetic cannabinoids outside the study during the 6-week intervention
• Individuals with HIV must meet the following criteria

• Virally suppressed on stable ART for at least 6 months and have no more than 1 prior event of virologic failure (i.e., required change in ARTs due to virologic failure)
• Stage 1 or 2 infection
• Have a "normal" CD4 count defined as ≥350 cells/microliter
• No significant history of ART regimen adherence challenges
• Ability to adhere to the study visit schedule.

Exclusion Criteria

• Exclusion criteria will be: any substance use disorder (abuse or dependence) other than cannabis in the last 30 days;
• Significant cognitive impairment such as Dementia, including Alzheimer's disease
• Pregnancy or lactation, or unwillingness to prevent pregnancy during the trial; refusal to maintain highly effective contraceptive methods (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner) during the study for persons of child-bearing potential or those with partners of child-bearing potential
• Evidence of moderately or worse compromised liver or kidney function, including moderate (Child-Hugh B) or severe (Child-Hugh C) hepatic impairment and AST and ALT above ULN and total bilirubin above ULN;
• Evidence of significant cardiovascular risk, resting heart rate \<50 or >110 beats per minute, uncontrolled hypertension (systolic blood pressure \<80 or >140 mmHg; diastolic blood pressure \<50 or >90 mmHg), history of myocardial infarction, congestive heart failure, or arrhythmia);
• Evidence of chronic pulmonary disease requiring supplemental oxygen;
• Active, recent, or remote medical history of hepatobiliary-related illness, including elevated transaminase levels above 3 times the upper limit of normal accompanied by elevations in total bilirubin above 2 times the upper limit of normal at screening;
• Insulin dependent diabetics
• Allergy to the study drugs or any of their constituents including sesame
• Use of medications with absolute contraindicated or potential significant interactions
• Use of sedating medications
• Weighing less than 60 kg at screening to minimize the risk of elevated transaminases as a result of exposure to cannabidiol;
• Active, uncontrolled psychiatric disorder with psychotic features, severe depression, or suicidality; Participants will be excluded if they have had a history of suicide attempt, recent suicidal ideation or behavior as indexed by their Beck Depression Inventory-II (BDI-II) score is greater than or equal to 29 (severe depression).
• Neurologic disorder that could compromise interpretation of study findings, including uncontrolled seizure disorder (active seizures within the past 3 months), multiple sclerosis, Parkinson's disease, Alzheimer's disease, and recent (past 3 months) cerebral infarction or hemorrhage with neurological sequelae.