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Neuroimaging in cannabis use: a systematic review of the literature

  • R. Martín-Santos (a1) (a2) (a3), A. B. Fagundo (a2) (a4), J. A. Crippa (a1) (a3) (a5), Z. Atakan (a1) (a3), S. Bhattacharyya (a1), P. Allen (a1), P. Fusar-Poli (a1), S. Borgwardt (a1) (a6), M. Seal (a1) (a7), G. F. Busatto (a8) and P. McGuire (a1) (a3)...



We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug.


We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy.


Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls.


Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reported.


Corresponding author

*Address for correspondence: Dr R. Martín-Santos, Department of Psychiatry, Institute of Neurosciences, Hospital Clinic, IDIBAPS, CIBERSAM, Villarroel, 170, 08036 Barcelona, Spain. (Email:


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Aasly, J, Storsaeter, O, Nilsen, G, Smevik, O, Rinck, P (1993). Minor structural brain changes in young drug abusers. A magnetic resonance study. Acta Neurologica Scandinavica 87, 210214.
Amen, DG, Waugh, M (1998). High resolution brain SPECT imaging of marijuana smokers with AD/HD. Journal of Psychoactive Drugs 30, 209214.
Arnone, D, Barrick, TR, Chengappa, S, Mackay, CE, Clark, CA, Abou-Saleh, MT (2008). Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. Neuroimage 41, 10671074.
Arseneault, L, Cannon, M, Witton, J, Murray, RM (2004). Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry 184, 110117.
Ashtari, M, Cervellione, K, Cottone, J, Ardekani, BA, Kumra, S (2009). Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use. Journal of Psychiatric Research 43, 189204.
Bechara, A, Dolan, S, Denburg, N, Hindes, A, Anderson, SW, Nathan, PE (2001). Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia 39, 376389.
Berger, A, Posner, MI (2000). Pathologies of brain attentional networks. Neuroscience and Biobehavioral Reviews 24, 35.
Block, RI, O'Leary, DS, Ehrhardt, JC, Augustinack, JC, Ghoneim, MM, Arndt, S, Hall, JA (2000 a). Effects of frequent marijuana use on brain tissue volume and composition. Neuroreport 11, 491496.
Block, RI, O'Leary, DS, Hichwa, RD, Augustinack, JC, Boles Ponto, LL, Ghoneim, MM, Arndt, S, Hurtig, RR, Watkins, GL, Hall, JA, Nathan, PE, Andreasen, NC (2002). Effects of frequent marijuana use on memory-related regional cerebral blood flow. Pharmacology, Biochemistry, and Behavior 72, 237250.
Block, RI, O'Leary, DS, Hichwa, RD, Augustinack, JC, Ponto, LL, Ghoneim, MM, Arndt, S, Ehrhardt, JC, Hurtig, RR, Watkins, GL, Hall, JA, Nathan, PE, Andreasen, NC (2000 b). Cerebellar hypoactivity in frequent marijuana users. Neuroreport 11, 749753.
Bolla, KI, Brown, K, Eldreth, D, Tate, K, Cadet, JL (2002). Dose-related neurocognitive effects of marijuana use. Neurology 59, 13371343.
Bolla, KI, Eldreth, DA, Matochik, JA, Cadet, JL (2005). Neural substrates of faulty decision-making in abstinent marijuana users. Neuroimage 26, 480492.
Borgwardt, SJ, Allen, P, Bhattacharyya, S, Fusar-Poli, P, Crippa, JA, Seal, ML, Fraccaro, V, Atakan, Z, Martin-Santos, R, O'Carroll, C, Rubia, K, McGuire, PK (2008). Neural basis of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD): effects during response inhibition. Biological Psychiatry 64, 966973.
Bossong, MG, van Berckel, BN, Boellaard, R, Zuurman, L, Schuit, RC, Windhorst, AD, van Gerven, JM, Ramsey, NF, Lammertsma, AA, Kahn, RS (2009). Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology 34, 759766.
Campbell, AM, Evans, M, Thomson, JL, Williams, MJ (1971). Cerebral atrophy in young cannabis smokers. Lancet 2, 12191224.
Chang, L, Chronicle, EP (2007). Functional imaging studies in cannabis users. Neuroscientist 13, 422432.
Chang, L, Yakupov, R, Cloak, C, Ernst, T (2006). Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation. Brain 129, 10961112.
Co, BT, Goodwin, DW, Gado, M, Mikhael, M, Hill, SY (1977). Absence of cerebral atrophy in chronic cannabis users. Evaluation by computerized transaxial tomography. Journal of the American Medical Association 237, 12291230.
Crippa, JA, Lacerda, AL, Amaro, E, Busatto, FG, Zuardi, AW, Bressan, RA (2005). Brain effects of cannabis – neuroimaging findings [in Portuguese]. Revista Brasileira de Psiquiatria 27, 7078.
Crippa, JA, Zuardi, AW, Garrido, GE, Wichert-Ana, L, Guarnieri, R, Ferrari, L, Azevedo-Marques, PM, Hallack, JE, McGuire, PK, Filho Busatto, G (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology 29, 417426.
DeLisi, LE (2008). The effect of cannabis on the brain: can it cause brain anomalies that lead to increased risk for schizophrenia? Current Opinion in Psychiatry 21, 140150.
DeLisi, LE, Bertisch, HC, Szulc, KU, Majcher, M, Brown, K, Bappal, A, Ardekani, BA (2006). A preliminary DTI study showing no brain structural change associated with adolescent cannabis use. Harm Reduction Journal 3, 17.
Eldreth, DA, Matochik, JA, Cadet, JL, Bolla, KI (2004). Abnormal brain activity in prefrontal brain regions in abstinent marijuana users. Neuroimage 23, 914920.
Freund, TF, Katona, I, Piomelli, D (2003). Role of endogenous cannabinoids in synaptic signaling. Physiological Reviews 83, 10171066.
Fusar-Poli, P, Crippa, JA, Bhattacharyya, S, Borgwardt, SJ, Allen, P, Martin-Santos, R, Seal, M, Surguladze, SA, O'Carrol, C, Atakan, Z, Zuardi, AW, McGuire, PK (2009). Distinct effects of (delta)9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Archives of General Psychiatry 66, 95105.
Gonzalez, R (2007). Acute and non-acute effects of cannabis on brain functioning and neuropsychological performance. Neuropsychology Review 17, 347361.
Gorelick, DA, Heishman, SJ (2006). Methods for clinical research involving cannabis administration. Methods in Molecular Medicine 123, 235253.
Gruber, SA, Yurgelun-Todd, DA (2005). Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation. Brain Research. Cognitive Brain Research 23, 107118.
Hall, W, Solowij, N (1998). Adverse effects of cannabis. Lancet 352, 16111616.
Hannerz, J, Hindmarsh, T (1983). Neurological and neuroradiological examination of chronic cannabis smokers. Annals of Neurology 13, 207210.
Hermann, D, Sartorius, A, Welzel, H, Walter, S, Skopp, G, Ende, G, Mann, K (2007). Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users. Biological Psychiatry 61, 12811289.
Hirst, RA, Lambert, DG, Notcutt, WG (1998). Pharmacology and potential therapeutic uses of cannabis. British Journal of Anaesthesia 81, 7784.
Hollister, LE (1986). Health aspects of cannabis. Pharmacological Reviews 38, 120.
Jacobsen, LK, Mencl, WE, Westerveld, M, Pugh, KR (2004). Impact of cannabis use on brain function in adolescents. Annals of the New York Academy of Sciences 1021, 384390.
Jacobsen, LK, Pugh, KR, Constable, RT, Westerveld, M, Mencl, WE (2007). Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users. Biological Psychiatry 61, 3140.
Jager, G, Kahn, RS, Van Den Brink, W, Van Ree, JM, Ramsey, NF (2006). Long-term effects of frequent cannabis use on working memory and attention: an fMRI study. Psychopharmacology (Berlin) 185, 358368.
Jager, G, Van Hell, HH, De Win, MM, Kahn, RS, Van Den Brink, W, Van Ree, JM, Ramsey, NF (2007). Effects of frequent cannabis use on hippocampal activity during an associative memory task. Journal of the European College of Neuropsychopharmacology 17, 289297.
Kanayama, G, Rogowska, J, Pope, HG, Gruber, SA, Yurgelun-Todd, DA (2004). Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study. Psychopharmacology (Berlin) 176, 239247.
Kuehnle, J, Mendelson, JH, Davis, KR, New, PF (1977). Computed tomographic examination of heavy marijuana smokers. Journal of the American Medical Association 237, 12311232.
Li, CS, Milivojevic, V, Constable, RT, Sinha, R (2005). Recent cannabis abuse decreased stress-induced BOLD signals in the frontal and cingulate cortices of cocaine dependent individuals. Psychiatry Research 140, 271280.
Lundqvist, T (2005). Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacology, Biochemistry, and Behavior 81, 319330.
Lundqvist, T, Jonsson, S, Warkentin, S (2001). Frontal lobe dysfunction in long-term cannabis users. Neurotoxicology and Teratology 23, 437443.
Mathew, RJ, Tant, S, Burger, C (1986). Regional cerebral blood flow in marijuana smokers. British Journal of Addiction 81, 567571.
Mathew, RJ, Wilson, WH (1993). Acute changes in cerebral blood flow after smoking marijuana. Life Sciences 52, 757767.
Mathew, RJ, Wilson, WH, Chiu, NY, Turkington, TG, DeGrado, TR, Coleman, RE (1999). Regional cerebral blood flow and depersonalization after tetrahydrocannabinol administration. Acta Psychiatrica Scandinavica 100, 6775.
Mathew, RJ, Wilson, WH, Coleman, RE, Turkington, TG, DeGrado, TR (1997). Marijuana intoxication and brain activation in marijuana smokers. Life Sciences 60, 20752089.
Mathew, RJ, Wilson, WH, Humphreys, DF, Lowe, JV, Wiethe, KE (1992 a). Regional cerebral blood flow after marijuana smoking. Journal of Cerebral Blood Flow and Metabolism 12, 750758.
Mathew, RJ, Wilson, WH, Humphreys, DF, Lowe, JV, Wiethe, KE (1992 b). Changes in middle cerebral artery velocity after marijuana. Biological Psychiatry 32, 164169.
Mathew, RJ, Wilson, WH, Tant, SR (1989). Acute changes in cerebral blood flow associated with marijuana smoking. Acta Psychiatrica Scandinavica 79, 118128.
Mathew, RJ, Wilson, WH, Turkington, TG, Coleman, RE (1998). Cerebellar activity and disturbed time sense after THC. Brain Research 797, 183189.
Mathew, RJ, Wilson, WH, Turkington, TG, Hawk, TC, Coleman, RE, DeGrado, TR, Provenzale, J (2002). Time course of tetrahydrocannabinol-induced changes in regional cerebral blood flow measured with positron emission tomography. Psychiatry Research 116, 173185.
Matochik, JA, Eldreth, DA, Cadet, JL, Bolla, KI (2005). Altered brain tissue composition in heavy marijuana users. Drug and Alcohol Dependence 77, 2330.
Murphy, K, Dixon, V, LaGrave, K, Kaufman, J, Risinger, R, Bloom, A, Garavan, H (2006). A validation of event-related FMRI comparisons between users of cocaine, nicotine, or cannabis and control subjects. American Journal of Psychiatry 163, 12451251.
Nestor, L, Roberts, G, Garavan, H, Hester, R (2008). Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 13281339.
O'Leary, DS, Block, RI, Flaum, M, Schultz, SK, Boles Ponto, LL, Watkins, GL, Hurtig, RR, Andreasen, NC, Hichwa, RD (2000). Acute marijuana effects on rCBF and cognition: a PET study. Neuroreport 11, 38353841.
O'Leary, DS, Block, RI, Koeppel, JA, Flaum, M, Schultz, SK, Andreasen, NC, Ponto, LB, Watkins, GL, Hurtig, RR, Hichwa, RD (2002). Effects of smoking marijuana on brain perfusion and cognition. Neuropsychopharmacology 26, 802816.
O'Leary, D, Block, RI, Koeppel, JA, Schultz, SK, Magnotta, VA, Boles Ponto, L, Watkins, FL, Hichwa, RD (2007). Effects of smoking marijuana on focal attention and brain flow. Human Psychopharmacology 22, 135148.
O'Leary, DS, Block, RI, Turner, BM, Koeppel, J, Magnotta, VA, Ponto, LB, Watkins, GL, Hichwa, RD, Andreasen, NC (2003). Marijuana alters the human cerebellar clock. Neuroreport 14, 11451151.
Pertwee, RG, Ross, RA (2002). Cannabinoid receptors and their ligands. Prostaglandins, Leukotrienes and Essential Fatty Acids 66, 101121.
Phan, KL, Angstadt, M, Golden, J, Onyewuenyi, I, Popovska, A, de Wit, H (2008). Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. Journal of Neuroscience 28, 23132319.
Pillay, SS, Rogowska, J, Kanayama, G, Jon, DI, Gruber, S, Simpson, N, Cherayil, M, Pope, HG, Yurgelun-Todd, DA (2004). Neurophysiology of motor function following cannabis discontinuation in chronic cannabis smokers: an fMRI study. Drug and Alcohol Dependence 76, 261271.
Quickfall, J, Crockford, D (2006). Brain neuroimaging in cannabis use: a review. Journal of Neuropsychiatry and Clinical Neuroscience 18, 318332.
Ranganathan, M, D'Souza, DC (2006). The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berlin) 188, 425444.
Roser, P, Vollenweider, FX, Kawohl, W (2008). Potential antipsychotic properties of central cannabinoid (CB(1)) receptor antagonists. World Journal of Biological Psychiatry 7, 112.
Rypma, B, D'Esposito, M (2000). Isolating the neural mechanisms of age-related changes in human working memory. Nature Neuroscience 3, 509515.
Schneider, M (2008). Puberty as a highly vulnerable development period for the consequences of cannabis exposure. Addiction Biology 13, 253263.
Schweinsburg, AD, Schweinsburg, BC, Cheung, EH, Brown, GG, Brown, SA, Tapert, SF (2005). fMRI response to spatial working memory in adolescents with comorbid marijuana and alcohol use disorders. Drug and Alcohol Dependence 79, 201210.
Sevy, S, Smith, GS, Ma, Y, Dhawan, V, Chaly, T, Kingsley, PB, Kumra, S, Abdelmessih, S, Eidelberg, D (2008). Cerebral glucose metabolism and D2/D3 receptor availability in young adults with cannabis dependence measured with positron emission tomography. Psychopharmacology (Berlin) 197, 549556.
Sneider, JT, Pope, HG Jr., Silveri, MM, Simpson, NS, Gruber, SA, Yurgelun-Todd, DA (2006). Altered regional blood volume in chronic cannabis smokers. Experimental and Clinical Psychopharmacology 14, 422428.
Sneider, JT, Pope, HG Jr., Silveri, MM, Simpson, NS, Gruber, SA, Yurgelun-Todd, DA (2008). Differences in regional blood volume during a 28-day period of abstinence in chronic cannabis smokers. European Neuropsychopharmacology 18, 612619.
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. Journal of the American Medical Association 287, 11231131.
Tunving, K, Thulin, SO, Risberg, J, Warkentin, S (1986). Regional cerebral blood flow in long-term heavy cannabis use. Psychiatry Research 17, 1521.
Tzilos, GK, Cintron, CB, Wood, JB, Simpson, NS, Young, AD, Pope, HG Jr., Yurgelun-Todd, DA (2005). Lack of hippocampal volume change in long-term heavy cannabis users. American Journal on Addictions 14, 6472.
Vernon, PA (1983). Speed of information processing and general intelligence. Intelligence 7, 5370.
Volkow, ND, Fowler, JS, Wang, GJ (2003). The addicted human brain: insights from imaging studies. Journal of Clinical Investigation 111, 14441451.
Volkow, ND, Gillespie, H, Mullani, N, Tancredi, L, Grant, C, Ivanovic, M, Hollister, L (1991). Cerebellar metabolic activation by delta-9-tetrahydro-cannabinol in human brain: a study with positron emission tomography and 18F-2-fluoro-2-deoxyglucose. Psychiatry Research 40, 6978.
Volkow, ND, 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 Research 67, 2938.
Voruganti, LN, Slomka, P, Zabel, P, Mattar, A, Awad, AG (2001). Cannabis induced dopamine release: an in-vivo SPECT study. Psychiatry Research 107, 173177.
Voytek, B, Berman, SM, Hassid, BD, Simon, SL, Mandelkern, MA, Brody, AL, Monterosso, J, Ling, W, London, ED (2005). Differences in regional brain metabolism associated with marijuana abuse in methamphetamine abusers. Synapse 57, 113115.
Ward, PB, Solowij, N, Peters, R, Otton, J, Chesher, G, Grenyer, B (2002). An fMRI study of regional brain volumes in long-term cannabis users. Journal of Psychopharmacology 16 (Suppl. 3), A56.
Watson, SJ, Benson, JA Jr., Joy, JE (2000). Marijuana and medicine: assessing the science base: a summary of the 1999 Institute of Medicine report. Archives of General Psychiatry 57, 547552.
Weinstein, A, Brickner, O, Lerman, H, Greemland, M, Bloch, M, Lester, H, Chisin, R, Mechoulam, R, Bar-Hamburger, R, Freedman, N, Even-Sapir, E (2008). Brain imaging study of the acute effects of Delta9-tetrahydrocannabinol (THC) on attention and motor coordination in regular users of marijuana. Psychopharmacology (Berlin) 196, 119131.
Wiesbeck, GA, Taeschner, KL (1991). A cerebral computed tomography study of patients with drug-induced psychoses. European Archives of Psychiatry and Clinical Neuroscience 241, 8890.
Williamson, EM, Evans, FJ (2000). Cannabinoids in clinical practice. Drugs 60, 13031314.
Wilson, W, Mathew, R, Turkington, T, Hawk, T, Coleman, RE, Provenzale, J (2000). Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study. Journal of Addictive Diseases 19, 122.
Yücel, M, Solowij, N, Respondek, C, Whittle, S, Fornito, A, Pantelis, C, Lubman, DI (2008). Regional brain abnormalities associated with long-term heavy cannabis use. Archives of General Psychiatry 65, 694701.
Yurgelun-Todd, DA, Gruber, SA, Hanson, RA, Baird, AA, Renshaw, PF, Pope, HG (1998). Residual effects of marijuana use: an fMRI study. In Problems of drug dependence. Proceedings of the 60th Annual Scientific Meeting. The College on Problems of Drug Dependence (ed. Harris, L. S.). NIDA Research Monograph 179, 78.
Zuardi, AW (2006). History of cannabis as a medicine: a review. Revista Brasileira de Psiquiatria 28, 153157.
Zuardi, AW, Shirakawa, I, Finkelfarb, E, Karniol, IG (1982). Action of cannabidiol on the anxiety and others effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berlin) 76, 245250.


Neuroimaging in cannabis use: a systematic review of the literature

  • R. Martín-Santos (a1) (a2) (a3), A. B. Fagundo (a2) (a4), J. A. Crippa (a1) (a3) (a5), Z. Atakan (a1) (a3), S. Bhattacharyya (a1), P. Allen (a1), P. Fusar-Poli (a1), S. Borgwardt (a1) (a6), M. Seal (a1) (a7), G. F. Busatto (a8) and P. McGuire (a1) (a3)...


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