Cannabis Use, Cognition, and the Endocannabinoid System in HIV

Understanding how co-morbidities in persons with HIV (PWH) such as substance use affect risk-taking, decision-making, and other cognitive behaviors is important given implications for everyday functioning and transmission risk. The high prevalence of cannabis use in PWH, medicinally and recreationally, may indicate disease severity, impart therapeutic benefits, or adverse consequences. In fact, cannabis is recommended to those with HIV to alleviate nausea, improve appetite, relieve pain, and lift mood. To-date, the consequences of cannabis use in PWH remain unclear as do potential interactions with HIV treatments. In healthy participants, heavy cannabis use is associated with cognitive deficits e.g., risky decision-making, response disinhibition and inattention, but pro-cognitive effects in PWH may exist at mild use levels due to its anti-inflammatory and anti-excitotoxic properties. Furthermore, little has been done to determine the effects of cannabis use on the endocannabinoid (EC) system in general or in PWH. This study will determine the effects of the two primary cannabis constituents (Δ9-tetrahydrocannabinol \[THC\], cannabidiol \[CBD\]) vs. placebo on risky decision-making, response inhibition, reward learning, temporal perception, and motivation, plus EC and homovanillic acid (HVA; a surrogate for dopamine activity) levels in HIV+ and HIV- subjects. Participants with infrequent cannabis use will undergo baseline cognitive testing and biomarker assays with antiretrovirals (ART) use quantified. They will be randomized to a 5-day course of either THC, CBD, or placebo and return for follow-up testing and re-assaying of ECs and HVA levels.


Eligibility Criteria:
Inclusion Criteria

* Aged 18 and older
* Possess the capacity to provide informed consent to a set of neurobehavioral, neuromedical and cognitive assessment procedures. Individuals unable to provide such consent will not be enrolled into the study.
* HIV Status: HIV status will be determined using the MedMira Rapid Test (Halifax, Nova Scotia, Canada). If the result differs from the participant's self-report a confirmatory Western Blot will be performed.
* Infrequent use of cannabis, defined as 1-4 times per month. Must have used cannabis at least five times in the past two years without an adverse reaction.
* Willing to abstain from cannabis for at least 2 days prior the baseline visit. Although there is no definitive method for determining abstinence over this period, abstinence will be confirmed as best as possible by using an oral fluid testing device (Draeger 5000) employed by law enforcement officers to detect recent cannabis use. An oral fluid value of \> 5ng suggests recent use, although in some cases it has been reported that individuals may show \> 5ng up to 20 hours after use. Thus, should the oral fluid sample indicate \> 5ng THC, the assessment may be canceled and rescheduled.

Exclusion Criteria

* Inability to provide informed consent
* Significant chronic renal disease (unrelated to HIV), significant chronic pulmonary disease (unrelated to HIV), or Hepatitis C Virus infection
* Head injury with loss of consciousness for greater than 30 minutes or resulting in neurologic complications
* Seizure disorder
* Demyelinating diseases or other non-HIV neurological disorders
* Pregnancy
* Acute or recent or previous clinically disabling stroke or previous cerebrovascular events
* Lifetime history of schizophrenia or other psychotic disorders, or bipolar disorder.
* Beck Depression Inventory-II (BDI-II) score is greater than or equal to 29 (severe depression) or suicidal ideas are endorsed on the BDI-II or a Center for Epidemiological Studies-Depression Scale (CES-D) subscale measuring suicidal ideation
* Alcohol use disorder (moderate or severe) within the last 12 months
* For other substances besides alcohol and cannabis, moderate or severe substance use disorder within the past five years or a mild substance use disorder within the past 12 months.