Skip to main content

Advertisement

SpringerLink
Log in

Combined and Independent Effects of Chronic Marijuana Use and HIV on Brain Metabolites

  • Invited Review
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

The effects of chronic marijuana (MJ) use on brain function remain controversial. Because MJ is often used by human immunodeficiency virus (HIV) patients, the aim of this study was to evaluate whether chronic MJ use and HIV infection are associated with interactive or additive effects on brain chemistry and cognitive function. We evaluated 96 subjects (30 seronegative nondrug users, 24 MJ users, 21 HIV without MJ use, 21 HIV + MJ) using proton magnetic resonance spectroscopy and a battery of neuropsychological tests. The two primarily abstinent MJ user groups showed no significant differences on calculated estimates of lifetime grams of delta9-tetrahydrocannabinol exposure, despite some differences in usage pattern. The two HIV groups also had similar HIV disease severity (CD4 cell count, plasma viral load, HIV dementia staging, Karnofsky score). On two-way analyses of covariance, HIV infection (independent of MJ) was associated with trends for reduced N-acetyl aspartate (NA) in the parietal white matter and increased choline compounds (CHO) in the basal ganglia. In contrast, MJ (independent of HIV) was associated with decreased basal ganglia NA (−5.5%, p = 0.05), CHO (−10.6%, p = 0.04), and glutamate (−9.5%, p = 0.05), with increased thalamic creatine (+6.1%, p = 0.05). HIV + MJ was associated with normalization of the reduced glutamate in frontal white matter (interaction p = 0.01). After correction for age, education, or mood differences, MJ users had no significant abnormalities on neuropsychological test performance, and HIV subjects only had slower reaction times. These findings suggest chronic MJ use may lead to decreased neuronal and glial metabolites, but may normalize the decreased glutamate in HIV patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Adle-Biassette H, Chretien F, Wingertsmann L, Hery C, Ereau T, Scaravilli F, Tardieu M, Gray F (1999) Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage. Neuropathol. Appl. Neurobiol. 25:123–133

    Article  PubMed  CAS  Google Scholar 

  • Anonymous (1994) Army individual test battery: manual of directions and scoring. War Department, Adjutant General's Office, Washington, DC

  • Blair J, Spreen O (1989) The new adult reading test—revised manual. University of Victoria, Victoria, Canada

    Google Scholar 

  • Bolla K, Brown K, Eldreth D, Tate K, Cadet J (2002) Dose-related neurocognitive effects of marijuana use. Neurology 9:1337–1343

    Google Scholar 

  • Bolla K, Eldreth D, Matochik J, Cadet J (2005) Neural substrates of faulty decision-making in abstinent marijuana users. NeuroImage 26:480–492

    Article  PubMed  Google Scholar 

  • Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev. Neurosci. 15:289–298

    Article  PubMed  CAS  Google Scholar 

  • Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987) Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical and electron microscopical study of 100 autopsy cases. Acta Neuropathol 75:185–198

    Article  PubMed  CAS  Google Scholar 

  • Cabral GA, Dove Pettit DA (1998) Drugs and immunity: cannabinoids and their role in decreased resistance to infectious disease. J Neuroimmunol 83:116–123

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Poland R, Jenden D (1996) In vivo proton magnetic resonance spectroscopy of the normal human aging brain. Life Sci 58:2049–2056

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Strickland T, Mehringer CM (1999a) Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users. Am J Psychiatry 156:716–722

    CAS  PubMed  Google Scholar 

  • Chang L, Ernst T, Grob CS, Poland RE (1999b) Cerebral 1H MRS abnormalities in 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) users. J Magn Reson Imaging 10:521–526

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Leonido-Yee M, Walot I, Singer E (1999c) Cerebral metabolite abnormalities correlate with clinical severity of HIV-cognitive motor complex. Neurology 52:100–108

    PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Leonido-Yee M, Speck O (2000) Perfusion MRI detects rCBF abnormalities in early stages of HIV-cognitive motor complex. Neurology 54:389–396

    PubMed  CAS  Google Scholar 

  • Chang L, Ernst T, Witt M, Ames N, Jocivich J, Speck O, Gaiefsky M, Walot I, Miller E (2002) Relationships among cerebral metabolites, cognitive function and viral loads in antiretroviral-naïve HIV patients. NeuroImage 17:1638–1648

    Article  PubMed  Google Scholar 

  • Chang L, Tomasi D, Yakupov R, Lozar C, Arnold S, Caparelli E, Ernst T. Adaptation of the attention network in human immunodeficiency virus brain injury. Ann. Neurol. 56:259–272, 2004.

    Article  PubMed  Google Scholar 

  • Charalambous A, Marciniak G, Shiue C, Dewey S, Schlyer D, Wolf A, Makriyannis A (1991) PET studies in the primate brain and biodistribution in mice using (−)-5′-18F-delta 8-THC. Pharmacol Biochem Behav 40:503–507

    Article  PubMed  CAS  Google Scholar 

  • Copper J, Bloom F, Roth R (1996) The Biochemical Basis of Neuropharmacology seventh edition, Oxford University Press, Inc. New York

    Google Scholar 

  • Cristiani SA, Pukay-Martin ND, Bornstein RA (2004) Marijuana use and cognitive function in HIV-infected people. J Neuropsychiatry Clin Neurosci 16:330–335

    PubMed  Google Scholar 

  • Eldreth D, Matochik J, Cadet J, Bolla K (2004) Abnormal brain activity in prefrontal brain regions in abstinent marijuana users. NeuroImage 23:914–920

    Article  PubMed  Google Scholar 

  • Ernst T, Kreis R, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain. I. Compartments and water. J Magn Reson B102:1–8

    Google Scholar 

  • Ernst T, Chang L, Leonido-Yee M, Speck O (2000) Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1H MRS study. Neurology 54:1344–1349

    PubMed  CAS  Google Scholar 

  • Ernst T, Chang L, Arnold S (2003) Increased glial markers predict increased working memory network activation in HIV patients. NeuroImage 19:1686–1693

    Article  PubMed  CAS  Google Scholar 

  • Ferrarese C, Aliprandi A, Tremolizzo L, Stanzani L, De Micheli A, Dolara A, Frattola L (2001) Increased glutamate in CSF and plasma of patients with HIV dementia. Neurology 57:671–675

    PubMed  CAS  Google Scholar 

  • Goncharov I, Weiner L, Vogel Z (2005) Delta9-tetrahydrocannabinol increases C6 glioma cell death produced by oxidative stress. Neuroscience 134:567–574

    Article  PubMed  CAS  Google Scholar 

  • Grant I, Atkinson J, Hesselink J (1987) Evidence for early central nervous system involvement in the acquired immunodeficiency syndrome (AIDS) and other immunodeficiency virus (HIV) infections. Ann Intern Med 107:828–836

    PubMed  CAS  Google Scholar 

  • Grant I, Gonzalez R, Carey CL, Natarajan L, Wolfson T (2003) Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. J Int Neuropsychol Soc 9:679–689

    Article  CAS  PubMed  Google Scholar 

  • Gruber SA, Yurgelun-Todd DA (2005) Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation. Brain Res Cogn Brain Res 23:107–118

    Article  PubMed  Google Scholar 

  • Heaton R, Grant I, Butters N, White D, Kirson D, Atkinson J, McCutchan J, Taylor M, Kelly M, Ellis R (1995) The HNRC 500—neuropsychology of HIV infection at different stages. HIV Neurobehavioral Research Center. J Int Neuropsychol Soc 1:231–251

    PubMed  CAS  Google Scholar 

  • Ke Y, Streeter C, Nassar L, Sarid-Segal O, Hennen J, Yurgelun-Todd D, Awad L, Rendall M, Gruber S, Nason A, Mudrick M, Blank S, Meyer A, Knapp C, Ciraulo D, Renshaw P (2004) Frontal lobe GABA levels in cocaine dependence: a two-dimensional, J-resolved magnetic resonance spectroscopy study. Psychiatry Res 130:283–293

    Article  PubMed  CAS  Google Scholar 

  • Klein TW, Friedman H, Specter S (1998) Marijuana, immunity and infection. J Neuroimmunol 83:102–115

    Article  PubMed  CAS  Google Scholar 

  • Klein TW, Lane B, Newton CA, Friedman H (2000) The cannabinoid system and cytokine network. Proc Soc Exp Biol Med 225:1–8

    Article  PubMed  CAS  Google Scholar 

  • Kløve H (1963) Clinical neuropsychology. In: Forster F (ed) The Medical Clinics of North America, WB Saunders, New York, pp 110–125

    Google Scholar 

  • Kreis R, Ernst T, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain. II. Metabolite concentrations. J Magn Reson B102:9–19

    Google Scholar 

  • Lee JH, Garwood M, Menon R, Adriany G, Andersen P, Truwit CL, Ugurbil K (1995) High contrast and fast three-dimensional magnetic resonance imaging at high fields. Magn Reson Med 34:308–312

    Article  PubMed  CAS  Google Scholar 

  • Maccarrone M, Finazzi-Agro A (2003) The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis. Cell Death Differ 10:946–955

    Article  PubMed  CAS  Google Scholar 

  • Marsicano G, Moosmann B, Hermann H, Lutz B, Behl C (2002) Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. J Neurochem 80:448–456

    Article  PubMed  CAS  Google Scholar 

  • Martin E, Pitrak D, Pursell K, Mullane K, Novak R (1995) Delayed recognition memory span in HIV-1 infection. J Int Neuropsychol Soc 1:575–580

    Article  CAS  PubMed  Google Scholar 

  • Miller EN (1990) California Computerized Assessment Package. In Custom Edition, Norland Software, Los Angeles

    Google Scholar 

  • Miller EN, Selnes OA, McArthur JC, Satz P, Becker JT, Cohen BA, Sheridan K, Machado AM, Van Gorp WG, Visscher B (1990) Neuropsychological performance in HIV-1 infected homosexual men: the Multicenter AIDS Cohort Study (MACS). Neurology 40:197–203

    PubMed  CAS  Google Scholar 

  • O'Leary D, Block R, Koeppel J, Flaum M, Schultz S, Andreasen N, Ponto L, Watkins G, Hurtig R, Hichwa R (2002) Effects of smoking marijuana on brain perfusion and cognition. Neuropsychopharmacology 26:802–816

    Article  PubMed  Google Scholar 

  • Patel N, Moldow R, Patel J, Wu G, Chang S (1998) Arachidonylethanolamide (AEA) activation of FOS proto-oncogene protein immunoreactivity in the rat brain. Brain Res 797:225–233

    Article  PubMed  CAS  Google Scholar 

  • Pistis M, Ferraro L, Pira L, Flore G, Tanganelli S, Gessa GL, Devoto P (2002) Delta(9)-tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: an in vivo microdialysis study. Brain Res 948:155–158

    Article  PubMed  CAS  Google Scholar 

  • Pope HJ, Yurgelun-Todd D (1996) The residual cognitive effects of heavy marijuana use in college students. J Am Med Assoc 275:521–527

    Article  CAS  Google Scholar 

  • Pope HJ, Gruber A, Hudson J, Huestis M, Yurgelun-Todd D (2001) Neuropsychological performance in long-term cannabis users. Arch Gen Psychiatry 58:909–915

    Article  PubMed  Google Scholar 

  • Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–592

    Article  PubMed  CAS  Google Scholar 

  • Provencher S (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672

    Article  PubMed  CAS  Google Scholar 

  • Radloff LL (1997) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401

    Article  Google Scholar 

  • Rey A (1941) L'examen psycholoqiue dans les cas d'encephalopathie traumatique. Arch Psychol 28:286–340

    Google Scholar 

  • Rottenberg DA, Sidtis JJ, Strother SC, Schaper KA, Anderson JR, Nelson MJ, Price RW (1996)Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia. J Nucl Med 37:1133–1141

    PubMed  CAS  Google Scholar 

  • Shen M, Thayer SA (1999) Delta9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture. Mol Pharmacol 55:8–13

    PubMed  CAS  Google Scholar 

  • Smith A (1982) Symbol Digit Modalities Test: Western Psychological Services

  • Soher B, Hurd R, Sailasuta N, Barker P (1996) Quantitation of automated single-voxel proton MRS using cerebral water as an internal reference. Magn Reson Med 36:335–339

    Article  PubMed  CAS  Google Scholar 

  • Solowij N, Stephens RS, Roffman RA, Babor T, Kadden R, Miller M, Christiansen K, McRee B, Vendetti J (2002) Cognitive functioning of long-term heavy cannabis users seeking treatment. J Am Med Assoc 287:1123–1131

    Article  Google Scholar 

  • Stroop J (1935) Studies of interference in serial verbal reaction. J Exp Psychol 18:643–662

    Article  Google Scholar 

  • Tomasini MC, Ferraro L, Bebe BW, Tanganelli S, Cassano T, Cuomo V, Antonelli T (2002) Delta(9)-tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: involvement of CB(1) receptors. J Neurosci Res 68:449–453

    Article  PubMed  CAS  Google Scholar 

  • Tozzi V, Balestra P, Serraino D, Bellagamba R, Corpolongo A, Piselli P, Lorenzini P, Visco-Comandini U, Vlassi C, Quartuccio M, Giulianelli M, Noto P, Galgani S, Ippolito G, Antinori A, Narciso P (2005) Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART. AIDS Res Hum Retrovir 21:706–713

    Article  PubMed  Google Scholar 

  • Volkow N, Gillespie H, Mullani N, Tancredi L, Grant C, Valentine A, Hollister L (1996) Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication. Psychiatry Res 67:29–38

    Article  PubMed  CAS  Google Scholar 

  • Watson SJ, Benson JA Jr, Joy JE (2000) Marijuana and medicine: assessing the science base: a summary of the 1999 Institute of Medicine report. Arch Gen Psychiatry 57:547–552

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by funds from NIH [K24-DA16170, K02-DA16991, and T32 DA07316] and the Department of Energy (Office of Environmental Research). We are grateful to the research subjects who participated in this study. We also thank K. Warren and L. Zimmerman for subject recruitment, K. Leckova for subject evaluation, and S. Arnold, D. Tomasi, C. Lozar, and E. Caparelli for some of the MRS data acquisition.

Author information

Authors and Affiliations

  1. Department of Medicine, John A. Burns School of Medicine, Queen's University Tower, 1356 Lusitana Street, Honolulu, HI, 96813, USA

    L. Chang, C. Cloak, R. Yakupov & T. Ernst

Authors
  1. L. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Cloak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Yakupov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Ernst
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, L., Cloak, C., Yakupov, R. et al. Combined and Independent Effects of Chronic Marijuana Use and HIV on Brain Metabolites. Jrnl NeuroImmune Pharm 1, 65–76 (2006). https://doi.org/10.1007/s11481-005-9005-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-005-9005-z

Keywords

Search

Navigation