Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV
Caitlin Wei-Ming Watson, Emily W. Paolillo, Erin E. Morgan, Anya Umlauf, Erin E. Sundermann, Ronald J. Ellis, MD, Scott Letendre, Thomas D. Marcotte, Robert K. Heaton, and Igor Grant
Journal of Acquired Immune Deficiency Syndromes, 2020, 83, (1), 56–64.
Doi : 10.1097/QAI.0000000000002211
Background : Aging and HIV have adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of neurocognitive impairment (NCI). Previous research suggests the nonacute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti inflammatory properties. In the current study, we examined the independent and interactive effects of HIV and cannabis on NCI and the potential moderation of these effects by age.
Methods : Participants included 679 people living with HIV (PLHIV) and 273 people living without HIV (HIV2) (18–79 years old) who completed neurocognitive, neuromedical, and substance use assessments. NCI was defined as a demographically corrected global deficit score $ 0.5. Logistic regression models examined the effects of age, HIV, cannabis (history of cannabis substance use disorder and cannabis use in past year), and their 2-way and 3-way interactions on NCI.
Results : In logistic regression models, only a significant interaction of HIV X cannabis was detected (P = 0.02). Among PLHIV, cannabis was associated with a lower proportion of NCI (odds ratio = 0.53, 95% confidence interval = 0.33–0.85) but not among HIV2 individuals (P = 0.40). These effects did not vary by age.
Conclusions : Findings suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV. Further investigations are needed to refine the effects of dose, timing, and cannabis compound on this relationship, which could inform guidelines for cannabis use among populations vulnerable to cognitive decline.
Key Words : cannabis, marijuana, HIV/AIDS, NeuroAIDS, cognition, HIV associated neurocognitive disorders
The advent of combination antiretroviral therapy (cART) has allowed people living with HIV (PLHIV) who have stable access to HIV treatment to achieve life expectancies near those without HIV.1 Despite medical advancements, neurocognitive impairment (NCI) remains prevalent, affecting 25%–50% of PLHIV,2,3 with highest rates among older PLHIV.4,5 Older age and HIV infection are each independently associated with central nervous system (CNS) injury, including increased inflammation and subsequent neural damage.6,7 Together, aging with HIV seems to inflict additive, or possible synergistic, detrimental effects on the CNS, leading to substantially increased risk of NCI.8,9 Clinically, NCI among PLHIV is associated with impairments in everyday functioning (eg, medication management)10,11 that can impact progression of HIV, subsequent transmissibility, and even confer increased risk of early mortality. Thus, understanding factors that may increase risk of or resilience against NCI among PLHIV is vital to maintaining optimal health in this population.
Cannabis use/exposure represents one modifiable behavioral factor worthy of investigation as an agent of NCI risk or resilience. Cannabis use is highly prevalent among PLHIV, with self-reported use in the past year almost three times greater than that of the general population in the United States (U.S.).12 Many PLHIV report the use of cannabis to ameliorate symptoms of HIV/AIDS such as neuropathic pain, nausea, mood problems, and appetite and weight loss.13,14 Among older adults, medicinal cannabis use has also increased as state-based legalization of medical and recreational cannabis has expanded in the U.S.15,16 Among the numerous recent studies examining chronic effects (ie, “residual” effects observed in the absence of acute intoxication) of cannabis use on neurocognition in the general population, results are highly variable. Although large scale reviews indicate that the most consistent adverse effect of cannabis use is on verbal learning and memory;17,18 chronic effects on all other neurocognitive domains (eg, executive function) vary widely by study, with many reporting no differences between cannabis users and non-users. A metaanalysis reported no residual negative effect of cannabis use on any neuro-cognitive domain after 25 days of abstinence,19 suggesting that some previous conclusions about permanence of adverse cannabis effects on cognition might not have sufficiently adjusted for recency of use. Some variations in neurocognitive outcomes may be potentially explained by relevant factors that differ within and across studies, such as amount of cannabis use, type and potency of cannabis product, and the context of use (eg, age of use; concurrently with other substances; in the presence of HIV disease or other medical conditions). These potential moderating factors are understudied, and their examination may support possible conditional effects of cannabis use on neurocognitive function.20
For example, previous research has shown that in certain conditions known to have detrimental effects on cognition (eg, methamphetamine use; schizophrenia), cannabis exposure does not compound these detrimental effects and may even be associated with reduced risk of NCI.21,22
Although there is some evidence that cannabis exposure may reduce neural injury by decreasing excitotoxicity and neuroinflammation,23,24 studies examining this in the context of HIV disease and the downstream neurocognitive effects of cannabis use are sparse and inconsistent, with reported effects ranging from adverse to protective.25–27 Furthermore, we are unaware of any studies examining chronic effects of cannabis on neurocognition in the context of HIV and aging. Given the current literature, one plausible hypothesis is that in the context of aging and HIV (two processes in which inflammation plays a role), cannabis exposure will relate to better cognitive outcomes compared to younger PLHIV and HIV2 older adults without cannabis exposure.
The current study examined the combined impact of cannabis, HIV, and aging on cognition. The first aim was to examine rates of NCI across 4 groups categorized by HIV status and cannabis exposure (CAN+; CAN2). We hypothesized (1) among HIV2 groups, NCI rates will not differ between cannabis groups, whereas (2) among PLHIV groups, the CAN+ group will have lower rates of NCI compared with the CAN2 group. In our second aim, we examined whether the effects of HIV or cannabis exposure on NCI were moderated by age in a model controlling for relevant predictors of NCI. We hypothesized we would detect a 3- way age X HIV X cannabis interaction such that cannabis exposure would relate to less NCI among younger and older PLHIV, but the magnitude of the association would be greater
among older PLHIV, and cannabis exposure would be unrelated to NCI among younger and older HIV2 individuals.
In our third study aim, we examined the effects of cannabis exposure by cognitive domain among any groups showing differential relationships between cannabis exposure and NCI in study aim 2.