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

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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

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Acknowledgements

This work was supported by grants from the National Institutes of Health. National Institute of Drug Abuse: P50 DA026306 (Translational Methamphetamine AIDS Research Center [TMARC]) to IG, R01 DA036164 and R01 DA047822 to MCGM, K23 DA037793 and R01 DA047879 to JEI; National Institute of Mental Health: K01 MH115819 to JAF, P30 MH062512 to JEI, R01 MH087332, R01 MH104131, and R01 MH105330 to MK. Stipend support to RS is funded by National Institute of Aging award F31 AG064989.

We thank the HIV Neurobehavioral Research Program and TMARC investigators that graciously provided material for producing manuscript figures. Specifically, we thank Ronald J. Ellis, James Kesby, David J. Moore, Emily W. Paolillo, Mary K. Swinton, and Caitlin Wei-Ming Watson.

The Translational Methamphetamine AIDS Research Center (TMARC) is supported by Center award P50DA026306 from the National Institute on Drug Abuse (NIDA) and is affiliated with the University of California, San Diego (UCSD), the Sanford-Burnham Medical Discovery Institute (SBMDI), and the University of California, Riverside (UCR). The TMARC comprises: Administrative Coordinating Core (ACC) – Executive Unit: Director – Igor Grant, M.D.; Co-Directors – Ronald J. Ellis, M.D., Ph.D., Scott L. Letendre, M.D., and Cristian L. Achim, M.D., Ph.D.; Center Manager – Mariana Cherner, Ph.D.; Associate Center Managers – Erin E. Morgan, Ph.D. and Jared Young, Ph.D.; Data Management and Information Systems (DMIS) Unit: Ian S. Abramson, Ph.D. (Unit Chief), Clint Cushman, B.A. (Unit Manager); ACC – Statistics Unit: Florin Vaida, Ph.D. (Unit Chief), Ian S. Abramson, Ph.D., Reena Deutsch, Ph.D., Anya Umlauf, M.S.; ACC – Participant Unit: J. Hampton Atkinson, M.D. (Unit Chief), Jennifer Marquie-Beck, M.P.H. (Unit Manager); Behavioral Assessment and Medical (BAM) Core – Neuromedical and Laboratory Unit (NLU): Scott L. Letendre, M.D. (Core Co-Director/NLU Chief), Ronald J. Ellis, M.D., Ph.D.; BAM Core – Neuropsychiatric Unit (NPU): Robert K. Heaton, Ph.D. (Core Co-Director/NPU Chief), J. Hampton Atkinson, M.D., Thomas D. Marcotte, Ph.D., Erin E. Morgan, Ph.D., Matthew Dawson (NPU Manager); Neuroimaging (NI) Core: Gregory G. Brown, Ph.D. (Core Director), Thomas T. Liu, Ph.D., Miriam Scadeng, Ph.D., Christine Fennema-Notestine, Ph.D., Sarah L. Archibald, M.A., John R. Hesselink, M.D., Mary Jane Meloy, Ph.D., Craig E.L. Stark, Ph.D.; Neuroscience and Animal Models (NAM) Core: Cristian L. Achim, M.D., Ph.D. (Core Director), Marcus Kaul, Ph.D., Virawudh Soontornniyomkij, M.D.; Pilot and Developmental (PAD) Core: Mariana Cherner, Ph.D. (Core Director), Stuart A. Lipton, M.D., Ph.D.; Project 1: Arpi Minassian, Ph.D. (Project Director), William Perry, Ph.D., Mark (A) Geyer, Ph.D., Jared W. Young, Ph.D.; Project 2: Amanda (B) Grethe, Ph.D. (Project Director), Susan F. Tapert, Ph.D., Assawin Gongvatana, Ph.D.; Project 3: Erin E. Morgan, Ph.D. (Project Director), Igor Grant, M.D.; Project 4: Samuel Barnes, Ph.D. (Project Director).; Project 5: Marcus Kaul, Ph.D. (Project Director), Ana Sanchez, Ph.D.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Government.

Funding

This work was supported by grants from the National Institutes of Health. National Institute of Drug Abuse: P50 DA026306 (Translational Methamphetamine AIDS Research Center [TMARC]) to IG, R01 DA036164 and R01 DA047822 to MCGM, K23 DA037793 and R01 DA047879 to JEI; National Institute of Mental Health: K01 MH115819 to JAF, P30 MH062512 to JEI, R01 MH087332, R01 MH104131, and R01 MH105330 to MK. Stipend support to RS is funded by National Institute of Aging award F31 AG064989. The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Government.

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Authors and Affiliations

  1. Department of Psychiatry, HIV Neurobehavioral Research Program, University of California, San Diego, San Diego, CA, USA

    Rowan Saloner, Jerel Adam Fields, Jennifer E. Iudicello, Sofie von Känel, Mariana Cherner, Scott L. Letendre, Marcus Kaul & Igor Grant

  2. Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego , San Diego, CA, USA

    Rowan Saloner

  3. San Diego Biomedical Research Institute, San Diego, CA, USA

    Maria Cecilia Garibaldi Marcondes

  4. Division of Biomedical Sciences, University of California, Riverside, Riverside, CA, USA

    Marcus Kaul

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Saloner, R., Fields, J.A., Marcondes, M.C.G. et al. Methamphetamine and Cannabis: A Tale of Two Drugs and their Effects on HIV, Brain, and Behavior. J Neuroimmune Pharmacol 15, 743–764 (2020). https://doi.org/10.1007/s11481-020-09957-0

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