Methamphetamine and Cannabis: A Tale of Two Drugs and their Effects on HIV, Brain, and Behavior

Authors:
  • TGthe Translational Methamphetamine AIDS Research Center (TMARC) Group
    the Translational Methamphetamine AIDS Research Center (TMARC) Group
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Abstract
HIV infection and drug use intersect epidemiologically, and their combination can result in complex effects on brain and behavior. The extent to which drugs affect the health of persons with HIV (PWH) depends on many factors including drug characteristics, use patterns, stage of HIV disease and its treatment, comorbid factors, and age. To consider the range of drug effects, we have selected two that are in common use by PWH: methamphetamine and cannabis. We compare the effects of methamphetamine with those of cannabis, to illustrate how substances may potentiate, worsen, or even buffer the effects of HIV on the CNS. Data from human, animal, and ex vivo studies provide insights into how these drugs have differing effects on the persistent inflammatory state that characterizes HIV infection, including effects on viral replication, immune activation, mitochondrial function, gut permeability, blood brain barrier integrity, glia and neuronal signaling. Moving forward, we consider how these mechanistic insights may inform interventions to improve brain outcomes in PWH. This review summarizes literature from clinical and preclinical studies demonstrating the adverse effects of METH, as well as the potentially beneficial effects of cannabis, on the interacting systemic (e.g., gut barrier leakage/microbial translocation, immune activation, inflammation) and CNS-specific (e.g., glial activation/neuroinflammation, neural injury, mitochondrial toxicity/oxidative stress) mechanisms underlying HIV-associated neurocognitive disorders
Funding Information
  • National Institute on Drug Abuse (P50 DA026306)
  • National Institute on Drug Abuse (R01 DA036164)
  • National Institute on Drug Abuse (R01 DA047822)
  • National Institute of Mental Health (K01 MH115819)
  • National Institute of Mental Health (R01 MH087332)
  • National Institute of Mental Health (R01 MH104131)
  • National Institute of Mental Health (R01 MH105330)
  • National Institute on Aging (F31 AG064989)
  • National Institute of Mental Health (P30 MH062512)
  • National Institute on Drug Abuse (K23 DA037793)
  • National Institute on Drug Abuse (R01 DA047879)

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