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  • Print publication year: 2011
  • Online publication date: November 2011

9 - Does cannabis cause lasting brain damage?

Summary

Cannabidiol ameliorates cognitive and motor impairment in mice with bile duct ligation, a model of hepatic encephalopathy. Cannabidiol administration may thus represent an adjunct treatment dealing with the central nervous system symptoms secondary to liver disease, along with other drugs improving liver function. Cannabidiol is also an inhibitor of ID-1 gene expression in aggressive breast cancer cells. Cannabigerol inhibits keratinocyte proliferation in a concentration-dependent manner. It is a partial agonist at both the CB1 and CB2 cannabinoid receptors. The CB2 receptor is involved in the pathogenesis of experimental encephalopathy in mice, caused by thioacetamide-induced acute liver failure. This is an animal model for hepatic encephalopathy, a neuropsychiatric syndrome. Cannabinoid and endocannabinoid chemistry, biochemistry and pharmacology continue to be active fields of research. While advances in these areas have widened our understanding of numerous physiological processes and pathological states, there are as yet no new major cannabinoid therapeutic agents.

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References

Allin, M., Khan, O., Walshe, M., et al. (2009) Cannabis smoking and white matter in healthy volunteers. Schizophr Bull, 35:201.
Amal, H., Fridman-Rozevich, L., Senn, R., et al. (2010) Long-term consequences of a single treatment of mice with an ultra-low dose of Δ9-tetrahydrocannabinol (THC). Behav Brain Res, 206:245–53.
Antonova, E., Kumari, V., Morris, R., et al. (2005) The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study. Biol Psychiatry, 58:457–67.
Angelucci, F., Ricci, V., Spalletta, G., et al. (2008) Reduced serum concentrations of nerve growth factor, but not brain-derived neurotrophic factor, in chronic cannabis abusers. Eur Neuropsychopharmacol, 18:882–7.
Arnone, D., Barrick, T.R., Chengappa, S., et al. (2008) Corpus callosum damage in heavy marijuana use: Preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. Neuroimage, 41:1067–74.
Ashtari, M., Cervellione, K., Cottone, J., et al. (2009) Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use. J Psychiatr Res, 43:189–204.
Bangalore, S.S., Prasad, K.M., Montrose, D.M., et al. (2008) Cannabis use and brain structural alterations in first episode schizophrenia – a region of interest, voxel based morphometric study. Schizophr Res, 99:1–6.
Bava, S., Frank, L.R., McQueeny, T., et al. (2009) Altered white matter microstructure in adolescent substance users. Psychiatry Res, 173:228–37.
Bava, S., Jacobus, J., Mahmood, O., et al. (2010) Neurocognitive correlates of white matter quality in adolescent substance users. Brain Cogn, 72:347–54.
Block, R.I., O’Leary, D.S., Ehrhardt, J.C., et al. (2000) Effects of frequent marijuana use on brain tissue volume and composition. Neuroreport, 11:491–6.
Cahn, W., Hulshoff Pol, H.E., Caspers, E., et al. (2004) Cannabis and brain morphology in recent-onset schizophrenia. Schizophr Res, 67:305–7.
Campbell, A.M.G., Evans, M., Thomson, J.L.G., et al. (1971) Cerebral atrophy in young cannabis smokers. Lancet, 298:1219–24.
Campbell, V.A. (2001) Tetrahydrocannabinol-induced apoptosis of cultured cortical neurones is associated with cytochrome c release and caspase-3 activation. Neuropharmacology, 40:702–9.
Caspi, A., Moffitt, T.E., Cannon, M., et al. (2005) Moderation of the effect of adolescent onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene x environment interaction. Biol Psychiatry, 57:1117–27.
Chan, G.C., Hinds, T.R., Impey, S., et al. (1998) Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. J Neurosci, 18:5322–32.
Co, B.T., Goodwin, D.W., Gado, M., et al. (1977) Absence of cerebral atrophy in chronic cannabis users: Evaluation by computerized transaxial tomography. J Am Med Assoc, 237:1229–30.
Dalton, V.S. and Zavitsanou, K. (2010) Cannabinoid effects on CB1 receptor density in the adolescent brain: an autoradiographic study using the synthetic cannabinoid HU210. Synapse, DOI:10.1002/Syn.20801.
Dekker, N., Schmitz, N., Peters, B.D., et al. (2010) Cannabis use and callosal white matter structure and integrity in recent-onset schizophrenia. Psychiatry Res, 181:51–6.
DeLisi, L.E. (2008) The effect of cannabis on the brain: can it cause brain anomalies that lead to increased risk for schizophrenia?Curr Opin Psychiatry, 21:140–50.
DeLisi, L.E., Bertisch, H.C., Szulc, K.U., et al. (2006) A preliminary DTI study showing no brain structural change associated with adolescent cannabis use. Harm Reduct J, 3:17.
Downer, E., Boland, B., Fogarty, M., et al. (2001) Delta 9-tetrahydrocannabinol induces the apoptotic pathway in cultured cortical neurones via activation of the CB1 receptor. Neuroreport, 12:3973–8.
Downer, E.J. and Campbell, V.A. (2010) Phytocannabinoids, CNS cells and development: A dead issue?Drug Alcohol Rev, 29:91–8.
D’Souza, D.C., Abi-Saab, W.M., Madonick, S., et al. (2005) Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol Psychiatry, 57:594–608.
D’Souza, D.C., Perry, E., MacDougall, L., et al. (2004) The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology, 29:1558–72.
D’Souza, D.C., Pittman, B., Perry, E., et al. (2009) Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology, 202:569–78.
Egerton, A., Allison, C., Brett, R.R., et al. (2006) Cannabinoids and prefrontal cortical function: Insights from preclinical studies. Neurosci Biobehav Rev, 30:680–95.
Ellgren, M., Artmann, A., Tkalych, O., et al. (2008) Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol, 18:826–34.
Gruber, S.A. and Yurgelun-Todd, D.A. (2005) Neuroimaging of marijuana smokers during inhibitory processing: a pilot investigation. Cogn Brain Res, 23:107–18.
Gur, R.E., Keshavan, M.S. and Lawrie, S.M. (2007) Deconstructing psychosis with human brain imaging. Schizophr Bull, 33:921–31.
Hannerz, J. and Hindmarsh, T. (1983) Neurological and neuroradiological examination of chronic cannabis smokers. Ann Neurol, 13:207–10.
Harkany, T., Keimpema, E., Barabás, K., et al. (2008) Endocannabinoid functions controlling neuronal specification during brain development. Mol Cell Endocrinol, 286:S84–90.
Harper, J.W., Heath, R.G. and Myers, W.A. (1977) Effects of Cannabis sativa on ultrastructure of the synapse in monkey brain. J Neurosci Res, 3:87–93.
Heath, R.G., Fitzjarrell, A.T., Fontana, C.J., et al. (1980) Cannabis sativa: effects on brain function and ultrastructure in rhesus monkeys. Biol Psychiatry, 15:657–90.
Henquet, C., Rosa, A., Krabbendam, L., et al. (2006) An experimental study of catechol-O-methyltransferase Val158Met moderation of Δ-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology, 31:2748–57.
Hermann, D., Sartorius, A., Welzel, H., et al. (2007) Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users. Biol Psychiatry, 61:1281–89.
Hurlemann, R., Jessen, F., Wagner, M., et al. (2008) Interrelated neuropsychological and anatomical evidence of hippocampal pathology in the at-risk mental state. Psychol Med, 38:843–51.
Jacobus, J., McQueeny, T., Bava, S., et al. (2009) White matter integrity in adolescents with histories of marijuana use and binge drinking. Neurotoxicol Teratol, 31:349–55.
Jager, G., Van Hell, H.H., De Win, M.M., et al. (2007) Effects of frequent cannabis use on hippocampal activity during an associative memory task. Eur Neuropsychopharmacol, 17:289–97.
Kano, M., Ohno-Shosaku, T., HashimotodaniY., et al. (2009) Endocannabinoid-mediated control of synaptic transmission. Physiology Rev, 89:309–80.
Koethe, D., Gerth, C.W., Neatby, M.A., et al. (2006) Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness. Schizophr Res, 88:142–50.
Kuehnle, J., Mendelson, J.H., Davis, K.R., et al. (1977) Computed tomographic examination of heavy marijuana smokers. J Am Med Assoc, 237:1231–2.
Landfield, P.W., Cadwallader, L.B., Vinsant, S. (1988) Quantitative changes in hippocampal structure following long-term exposure to delta 9-tetrahydrocannabinol: possible mediation by glucocorticoid systems. Brain Res, 443:47–62.
Lawston, J., Borella, A., Robinson, J.K., et al. (2000) Changes in hippocampal morphology following chronic treatment with the synthetic cannabinoid WIN 55,212–2. Brain Res, 877:407–10.
Lorenzetti, V., Allen, N.B., Fornito, A., et al. (2009) Structural brain abnormalities in major depressive disorder: A selective review of recent MRI studies. J Affect Disord, 117:1–17.
Lorenzetti, V., Lubman, D.I., Whittle, S., et al. (2010) Structural MRI findings in cannabis users: what do we know?Subst Use Misuse, 45: 1787–808.
MacQueen, G.M., Campbell, S., McEwen, B.S., et al. (2005) Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Nat Acad Sci USA, 100:1387–92.
Martin-Santos, R., Fagundo, A.B., Crippa, J.A., et al. (2010) Neuroimaging in cannabis use: a systematic review of the literature. Psychol Medi, 40:383–98.
Mata, I., Perez-Iglesias, R., Roiz-Santiañez, R., et al. (2010) Gyrification brain abnormalities associated with adolescence and early-adulthood cannabis use. Brain Res, 1317:297–304.
Matochik, J.A., Eldreth, D.A., Cadet, D.A., et al. (2005) Altered brain tissue composition in heavy marijuana users. Drug Alcohol Depend, 77:23–30.
Medina, K.L., Nagel, B.J., Park, A., et al. (2007a) Depressive symptoms in adolescents: associations with white matter volume and marijuana use. J Child Psychol Psychiatry, 48, 592–600.
Medina, K.L., Schweinsburg, A.D., Cohen-Zion, M., et al. (2007b) Effects of alcohol and combined marijuana and alcohol use during adolescence on hippocampal volume and asymmetry. Neurotoxicol Teratol, 29:141–52.
Monnet-Tschudi, F., Hazekamp, A., Perret, N., et al. (2008) Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures. Toxicol Appl Pharmacol, 228:8–16.
Myers, W.A. and Heath, R.G. (1979) Cannabis sativa: ultrastructural changes in organelles of neurons in brain septal region of monkeys. J Neurosci Res, 4:9–17.
Nestor, P.G., Kubicki, M., Kuroki, N., et al. (2007) Episodic memory and neuroimaging of hippocampus and fornix in chronic schizophrenia. Psychiatry Res, 155:2128.
Potvin, S., Mancini-Marie, A., Fahim, C., et al. (2007) Increased striatal gray matter densities in patients with schizophrenia and substance use disorder: a voxel-based morphometry study. Psychiatry Res, 154:275–9.
Quinn, H.R., Matsumoto, I., Callaghan, P.D., et al. (2008). Adolescent rats find repeated Δ9-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure. Neuropsychopharmacology, 33:1113–26.
Rais, M., Cahn, W., Van Haren, N., et al. (2008) Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. Am J Psychiatry, 165:490–6.
Realini, N., Rubino, T. and Parolaro, D. (2009) Neurobiological alterations at adult age triggered by adolescent exposure to cannabinoids. Pharmacol Res, 60, 132–8.
Rubino, T., Realini, N., Braida, D, et al. (2009a) Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus, 19:763–72.
Rubino, T., Realini, N., Braida, D., et al. (2009b) The depressive phenotype induced in adult female rats by adolescent exposure to THC is associated with cognitive impairment and altered neuroplasticity in the prefrontal cortex. Neurotox Res, 15:567–607.
Rubino, T., Viganò, D., Realini, N., et al. (2008) Chronic delta(9)-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology, 33:2760–71.
Sarne, Y. and Keren, O. (2004) Are cannabinoid drugs neurotoxic or neuroprotective?Med Hypotheses, 63:187–92.
Sarne, Y. and Mechoulam, R. (2005) Cannabinoids: between neuroprotection and neurotoxicity. Curr Drug Targets CNS Neurol Disord, 4:677–84.
Scallet, A.C., Uemura, E., Andrews, A., et al. (1987) Morphometric studies of the rat hippocampus following chronic delta-9-tetrahydrocannabinol (THC). Brain Res, 436:193–8.
Schneider, M. (2008) Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure. Addict Biol, 13:253–63.
Skosnik, P.D., Grishnan, G.P. and Aydt, E.E. (2006) Psychophysiological evidence of altered neural synchronization in cannabis use: relationship to schizotypy. Am J Psychiatry, 163:1798–805.
Skosnik, P.D., Park, S., Dobbs, L., et al. (2008) Affect processing and positive syndrome schizotypy in cannabis users. Psychiatry Res, 157:279–82.
Skosnik, P.D., Spatz-Glenn, L. and Park, S. (2001) Cannabis use is associated with schizotypy and attentional disinhibition. Schizophr Res, 48:83–92.
Solowij, N., Yücel, M., Lorenzetti, V., et al. (2009) Structural brain alterations in cannabis users: Association with cognitive deficits and psychiatric symptoms. In Ritsner, M.S. (Ed) The Handbook of Neuropsychiatric Biomarkers, Endophenotypes, and Genes. Vol. II Neuroanatomical and Neuroimaging Endophenotypes and Biomarkers, (pp. 215–225). Dordrecht: Springer.
Solowij, N., Respondek, C., Battisti, R., et al. (2008) Visuospatial memory deficits in long term heavy cannabis users: relation to psychotic symptoms and regional brain volumes. Int J Neuropsychopharmacol, 11:242.
Solowij, N., Walterfang, M., Respondek, C., et al. (2010) Alterations of hippocampal shape in cannabis users with and without schizophrenia. Schizophr Res, 117:426.
Solowij, N., Yücel, M., RespondekC., et al. (2011) Cerebellar white matter changes in cannabis users with and without schizophrenia. Psychol Med. DOI: 10.1017/S003329171100050X.
Stefanis, C. (1976) Biological aspects of cannabis use. In Petersen, R.C., ed. The International Challenge of Drug Abuse, 149–178. Rockville, MD: National Institute on Drug Abuse.
Szeszko, P.R., Robinson, D.G., Sevy, S., et al. (2007) Anterior cingulate grey-matter deficits and cannabis use in first-episode schizophrenia. Brit J Psychiatry, 190:230–6.
Szeszko, P.R., Robinson, D.G., Ashtari, M., et al. (2008) Clinical and neuropsychological correlates of white matter abnormalities in recent onset schizophrenia. Neuropsychopharmacology, 33:976–84.
Thatcher, D.L., Pajtek, S., Chung, T., et al. (2010) Gender differences in the relationship between white matter organization and adolescent substance use disorders. Drug Alcohol Depend, 110:55–61.
Tselnicker, I., Keren, O., Hefetz, A., et al. (2007) A single low dose of tetrahydrocannabinol induces long-term cognitive deficits. Neurosci Lett, 411:108–11.
Tzilos, G.K., Cintron, C.B., Wood, J.B., et al. (2005) Lack of hippocampal volume change in long-term heavy cannabis users. Am J Addict, 14:64–72.
Villares, J. (2007) Chronic use of marijuana decreases cannabinoid receptor binding and mRNA expression in the human brain. Neuroscience, 145:323–34.
Wilson, W., Mathew, R., Turkington, T., et al. (2000) Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study. J Addict Dis, 19:1–22.
Yücel, M., Bora, E., Lubman, D.I., et al. (2010) The impact of cannabis use on cognitive functioning in patients with schizophrenia: A meta-analysis of existing findings and new data in a first-episode sample. Schizophr Bull, DOI:10.1093/schbul/sbq079.
Yücel, M., Solowij, N., Respondek, C., et al. (2008) Regional brain abnormalities associated with long-term heavy cannabis use. Arch Gen Psychiatry, 65:694–701.
Yücel, M., Zalesky, A., Takagi, M.J., et al. (2010) Age-related white-matter abnormalities in long-term inhalant misusing adolescents: a diffusion MRI comparison with cannabis users and drug-naive controls. J Psychiatry Neurosci, 35:409–12.
Zavitsanou, K., Wang, H., Dalton, V.S., et al. (2010) Cannabinoid administration increases 5HT1 receptor binding and mRNA expression in the hippocampus of adult but not adolescent rats. Neuroscience, 169:315–24.