Skip to main content
    • Aa
    • Aa

Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons


Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV−/METH+), HIV infected/methamphetamine nondependent (HIV+/METH−), and HIV negative/methamphetamine nondependent (HIV−/METH−). Study groups were comparable for age, education, and ethnicity, although the HIV−/METH− group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV− participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV−/METH+ (40%) and HIV+/METH− (38%) groups compared to the HIV−/METH− (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms. (JINS, 2004, 10, 1–14.)Note: Dr. Erin D. Bigler served as action editor during the course of this review.

Corresponding author
Reprint requests to: Igor Grant, MD, HIV Neurobehavioral Research Center, 150 West Washington Street, 2nd Floor, San Diego, CA 92103.
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Adams, K.M., Brown, G.G., & Grant, I. (1985). Analysis of covariance as a remedy for demographic mismatch of research subject groups: Some sobering simulations. Journal of Clinical and Experimental Neuropsychology, 7, 445462.

Alhassoon, O.M., Dupont, R.M., Schweinsburg, B.C., Taylor, M.J., Patterson, T.L., & Grant, I. (2001). Regional cerebral blood flow in cocaine- versus methamphetamine-dependent patients with a history of alcoholism. International Journal of Neuropsychopharmacology, 4, 105112.

Atkinson, J.H., Grant, I., Kennedy, C.J., Richman, D.D., Spector, S.A., & McCutchan, J.A. (1988). Prevalence of psychiatric disorders among men infected with human immunodeficiency virus: A controlled study. Archives of General Psychiatry, 45, 859864.

Benedict, R.H., Schretlen, D., Groninger, L., & Brandt, J. (1998). Hopkins Verbal Learning Test–Revised: Normative data and analysis of inter-form and test–retest reliability. Clinical Neuropsychologist, 12, 4355.

Bing, E.G., Burnam, A., Longshore, D., Fleishman, J.A., Sherbourne, C.D., London, A.S., Turner, B.J., Eggan, F., Beckman, R., Vitiello, B., Morton, S.C., Orlando, M., Bozzette, S.A., Ortiz-Barron, L., & Shapiro, M. (2001). Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Archives of General Psychiatry, 58, 721728.

Bloom, F.E. & Rausch, D.M. (1997). HIV in the brain: Pathology and neurobehavioral consequences (meeting report). Journal of Neurovirology, 3, 102109.

Borkowski, J.G., Benton, A.L., & Spreen, O. (1967). Word fluency and brain damage. Neuropsychologia, 5, 135140.

Davidson, C., Gow, A.J., Lee, T.H., & Ellinwood, E.H. (2001). Methamphetamine neurotoxicity: Necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Research Reviews, 36, 122.

Deutsch, R., Ellis, R.J., McCutchan, A., Marcotte, T.D., Letendre, S., Grant, I., & the HNRC Group. (2001). AIDS-associated mild neurocognitive impairment is delayed in the era of highly active antiretroviral therapy (HAART). AIDS, 15, 18981899.

Diehr, M.C., Heaton, R.K., Miller, W., & Grant, I. (1998). The Paced Auditory Serial Addition Task (PASAT): Norms for age, education, and ethnicity. Assessment, 5, 375387.

Dore, G.J., Correll, P.K., Li, Y., Kaldor, J.M., Cooper, D.A., & Brew, B.J. (1999). Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS, 13, 12491253.

Durvasula, R.S., Myers, H.F., Satz, P., Miller, E.N., Morgenstern, H., Richardson, M.A., Evans, G., & Forney, D. (2000). HIV-1, cocaine, and neuropsychological performance in African American men. Journal of the International Neuropsychological Society, 6, 322335.

Durvasula, R.S., Miller, E.N., Myers, H.F., & Wyatt, G.E. (2001). Predictors of neuropsychological performance in HIV positive women. Journal of Clinical and Experimental Neuropsychology, 23, 149163.

Eisch, A., O'Dell, S., & Marshall, J. (1996). Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine. Synapse, 22, 217225.

Ernst, T., Chang, L., Leonido-Yee, M., & Speck, O. (2000). Evidence for long-term neurotoxicity associated with methamphetamine abuse. Neurology, 54, 13441349.

Ferrando, S., Goggin, K., Sewell, M., Evans, S., Fishman, B., & Rabkin, J. (1998). Substance use disorders in gay/bisexual men with HIV and AIDS. American Journal on Addictions, 7, 5160.

Gladsjo, J.A., Schuman, C.C., Evans, J.D., Peavy, G.M., Miller, S.W., & Heaton, R.K. (1999). Norms for letter and category fluency: Demographic corrections for age, education, and ethnicity. Assessment, 6, 147178.

Gouzoulis-Mayfrank, E., Schreckenberger, M., Sabri, O., Arning, C., Thelen, B., Spitzer, M., Kovar, K.A., Hermle, L., Bull, U., & Sass, H. (1999). Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. Neuropsychopharmacology, 20, 565581.

Grant, I., Adams, K.M., Carlin, A.S., Rennick, P., Judd, L.L., & Schooff, K. (1978). The collaborative neuropsychological study of polydrug abusers. Archives of General Psychiatry, 35, 10631074.

Grant, I., Atkinson, J.H., Hesselink, J.R., Kennedy, C.J., Richman, D.D., Spector, S.A., & McCutchan, J.A. (1987). Evidence for early central nervous system involvement in the acquired deficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Studies with neuropsychologic testing and magnetic resonance imaging. Annals of Internal Medicine, 107, 828836.

Grassi, M.P., Clerici, F., Perin, C., Zocchetti, C., Cargnel, A., & Mangoni, A. (1995). HIV infection and drug use: Influence on cognitive function. AIDS, 9, 165170.

Grassi, M.P., Perin, C., Clerici, F., Zocchetti, C., Cargnel, A., & Mangoni, A. (1993). Neuropsychological performance in HIV-1-infected drug abusers. Acta Neurologica Scandinavica, 88, 119122.

Gronwall, D.M.A. (1977). Paced auditory serial-addition task: A measure of recovery from concussion. Perceptual and Motor Skills, 44, 367375.

Haughey, N.J., Nath, A., Mattson, M.P., Slevin, J.T., & Geiger, J.D. (2001). HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. Journal of Neurochemistry, 78, 457467.

Heaton, R.K., Grant, I., Butters, N., White, D.A., Kirson, D., Atkinson, J.H., McCutchan, J.A., Taylor, M.J., Kelly, M.D., Ellis, R.J., Wolfson, T., Velin, R., Marcotte, T.D., Hesselink, J.R., Jernigan, T.L., Chandler, J., Wallace, M., Abramson, I., & the HNRC Group. (1995). The HNRC 500–Neuropsychology of HIV infection at different disease stages. Journal of the International Neuropsychological Society, 1, 231251.

Heaton, R.K., Paulsen, J., McAdams, L.A., Kuck, J., Zisook, S., Braff, D., Harris, M.J., & Jeste, D.V. (1994). Neuropsychological deficits in schizophrenics: Relationship to age, chronicity, and dementia. Archives of General Psychiatry, 51, 469476.

Hesselgesser, J., Taub, D., Baskar, P., Greenberg, M., Hoxie, J., Kolson, D.L., & Horuk, R. (1998). Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1alpha is mediated by the chemokine receptor CXCR4. Current Biology, 8, 595598.

Itoh, K., Mehraein, P., & Weis, S. (2000). Neuronal damage of the substantia nigra in HIV-1 infected brains. Acta Neuropathologica (Berl), 99, 376384.

Iyo, M., Namba, H., Yanagisawa, M., Hirai, S., Yui, N., & Fukui, S. (1997). Abnormal cerebral perfusion in chronic methamphetamine abusers: A study using 99MTc-HMPAO and SPECT. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 21, 789796.

Jernigan, T.L., Archibald, S., Hesselink, J.R., Atkinson, J.H., Velin, R.A., McCutchan, J.A., Chandler, J., Grant, I., & the HNRC Group. (1993). Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. Archives of Neurology, 50, 250255.

Jonckheere, A.R. (1954). A distribution-free k-sample test against ordered alternatives. Biometricka, 41, 133145.

Marshall, J., O'Dell, S., & Weihmuller, F. (1993). Dopamine–glutamate interactions in methamphetamine-induced neurotoxicity. Journal of Neural Transmission-General Section, 91, 241254.

Martin, E.M., Sullivan, T.S., Reed, R.A., Fletcher, T.A., Pitrak, D.L., Weddington, W., & Harrow, M. (2001). Auditory working memory in HIV-1 infection. Journal of the International Neuropsychological Society, 7, 2026.

Maschke, M., Kastrup, O., Esser, S., Ross, B., Hengge, U., & Hufnagel, A. (2000). Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). Journal of Neurology, Neurosurgery, and Psychiatry, 69, 376380.

McKetin, R. & Mattick, R.P. (1997). Attention and memory in illicit amphetamine users. Drug and Alcohol Dependence, 48, 235242.

McKetin, R. & Mattick, R.P. (1998). Attention and memory in illicit amphetamine users: Comparison with non-drug-using controls. Drug and Alcohol Dependence, 50, 181184.

Ohmori, T., Abekawa, T., & Koyama, T. (1996). The role of glutamate in behavioral and neurotoxic effects of methamphetamine. Neurochemistry International, 29, 301307.

Peavy, G., Jacobs, D., Salmon, D.P., Butters, N., Delis, D.C., Taylor, M., Massman, P., Stout, J.C., Heindel, W.C., Kirson, D., Atkinson, J.H., Chandler, J.L., Grant, I., & the HNRC Group. (1994). Verbal memory performance of patients with human immunodeficiency virus infection: Evidence of subcortical dysfunction. Journal of Clinical and Experimental Neuropsychology, 16, 508523.

Rabkin, J.G. (1996). Prevalence of psychiatric disorders in HIV illness. International Review of Psychiatry, 8, 157166.

Rausch, D.M. & Stover, E.S. (2001). Neuroscience research in AIDS. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25, 231257.

Reyes, M.G., Faraldi, F., Senseng, C.S., Flowers, C., & Fariello, R. (1991). Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathologica (Berl), 82, 3944.

Rothrock, J.F., Rubenstein, R., & Lyden, P.D. (1988). Ischemic stroke associated with methamphetamine inhalation. Neurology, 38, 589592.

Rumbaugh, C.L., Bergeron, R.T., Scanlan, R.L., Teal, J.S., Segall, H.D., Fang, H.C., & McCormick, R. (1971). Cerebral vascular changes secondary to amphetamine abuse in the experimental animal. Radiology, 101, 345351.

Sacktor, N., Lyles, R.H., Skolasky, R., Kleeberger, C., Selnes, O.A., Miller, E.N., Becker, J.T., Cohen, B., McArthur, J.C., & the Multicenter AIDS Cohort Study. (2001). HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology, 56, 257260.

Sekine, Y., Iyo, M., Ouchi, Y., Matsunaga, T., Tsukada, H., Okada, H., Yoshikawa, E., Futatsubashi, M., Takei, N., & Mori, N. (2001). Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. American Journal of Psychiatry, 158, 12061214.

Simon, S.L., Domier, C.P., Sim, T., Richardson, K., Rawson, R.A., & Ling, W. (2002). Cognitive performance of current methamphetamine and cocaine abusers. Journal of Addictive Diseases, 21, 6174.

Stephans, S. & Yamamoto, B. (1994). Methamphetamine-induced neurotoxicity: Roles for glutamate and dopamine efflux. Synapse, 17, 203209.

Stout, J.C., Ellis, R.J., Jernigan, T.L., Archibald, S.L., Abramson, I., Wolfson, T., McCutchan, J.A., Wallace, M.R., Atkinson, J.H., Grant, I., & the HNRC Group. (1998). Progressive cerebral volume loss in human immunodeficiency virus infection: A longitudinal volumetric magnetic resonance imaging study. Archives of Neurology, 55, 161168.

Taylor, M.J., Alhassoon, O.M., Schweinsburg, B.C., Videen, J.S., Grant, I., & the HNRC Group. (2000). MR spectroscopy in HIV and stimulant dependence. Journal of the International Neuropsychological Society, 6, 8385.

Tracey, I., Hamberg, L.M., Guirnaraes, A.R., Hunter, G., Chang, I., Navia, B.A., & Gonzalez, R.G. (1998). Increased cerebral blood volume in HIV-positive patients detected by functional MRI. Neurology, 50, 18211826.

Volkow, N.D., Chang, L., Wang, G.J., Fowler, J.S., Franceschi, D., Sedler, M.J., Gatley, S.J., Hitzemann, R., Ding, Y.S., Wong, C., & Logan, J. (2001a). Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers. American Journal of Psychiatry, 158, 383389.

Volkow, N.D., Chang, L., Wang, G.J., Fowler, J.S., Leonido-Yee, M., Franceschi, D., Sedler, M.J., Gatley, S.J., Hitzemann, R., Ding, Y.S., Logan, J., Wong, C., & . Miller, E.N. (2001b). Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. American Journal of Psychiatry, 158, 377382.

von Giesen, H.J., Antke, C., Hefter, H., Wenserski, F., Seitz, R.J., & Arendt, G. (2000). Potential time course of human immunodeficiency virus type-1 associated minor motor deficits. Archives of Neurology, 57, 16011607.

White, D.A., Heaton, R.K., & Monsch, A.U. (1995). Neuropsychological studies of asymptomatic human immunodeficiency virus-type 1-infected individuals. Journal of the International Neuropsychological Society, 1, 304315.

Wilson, J.M., Kalasinsky, K.S., Levey, A.I., Bergeron, C., Reiber, G., Anthony, R.M., Schmunk, G.A., Shannak, K., Haycock, J.W., & Kish, S.J. (1996). Striatal and dopamine nerve terminal markers in human, chronic methamphetamine users. Natural Medicine, 2, 699703.

Woody, G.E., Donnell, D., Seage, G.R., Metzger, D., Marmor, M., Koblin, B.A., Buchbinder, S., Gross, M., Stone, B., & Judson, F.N. (1999). Non-injection substance use correlates with risky sex among men having sex with men. Data from HIVNET. Drug and Alcohol Dependence, 53, 197205.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
  • URL: /core/journals/journal-of-the-international-neuropsychological-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 7
Total number of PDF views: 29 *
Loading metrics...

Abstract views

Total abstract views: 176 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 30th May 2017. This data will be updated every 24 hours.