600
Views
87
CrossRef citations to date
0
Altmetric
Review

Cannabis and schizophrenia: towards a cannabinoid hypothesis of schizophrenia

&
Pages 1037-1048 | Published online: 09 Jan 2014

References

  • Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR (Text Revision). American Psychiatric Association (2004).
  • Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, “just the facts”: what we know in 2008 Part 1: overview. Schizophr. Res.100(1–3), 4–19 (2008).
  • Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc.86(8), 1646–1647 (1964).
  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature346(6284), 561–564 (1990).
  • Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature365(6441), 61–65 (1993).
  • Fride E, Foox A, Rosenberg E et al. Milk intake and survival in newborn cannabinoid CB1 receptor knockout mice: evidence for a “CB3” receptor. Eur. J. Pharmacol.461(1), 27–34 (2003).
  • Grotenhermen F. Cannabinoids. Curr. Drug Targets CNS Neurol. Disord.4(5), 507–530 (2005).
  • Devane WA, Hanus L, Breuer A et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science258(5090), 1946–1949 (1992).
  • Mechoulam R, Ben-Shabat S, Hanus L et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol.50(1), 83–90 (1995).
  • Krystal JH, D’Souza DC, Madonick S, Petrakis IL. Toward a rational pharmacotherapy of comorbid substance abuse in schizophrenic patients. Schizophr. Res.35(Suppl.), S35–S49 (1999).
  • Blanchard JJ, Squires D, Henry T et al. Examining an affect regulation model of substance abuse in schizophrenia. The role of traits and coping. J. Nerv. Ment. Dis.187(2), 72–79 (1999).
  • Stirling J, Lewis S, Hopkins R, White C. Cannabis use prior to first onset psychosis predicts spared neurocognition at 10-year follow-up. Schizophr. Res.75(1), 135–137 (2005).
  • McCleery A, Addington J, Addington D. Substance misuse and cognitive functioning in early psychosis: a 2 year follow-up. Schizophr. Res.88(1–3), 187–191 (2006).
  • D’Souza DC, Abi-Saab WM, Madonick S et al. Δ-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol. Psychiatry57(6), 594–608 (2005).
  • Potvin S, Joyal CC, Pelletier J, Stip E. Contradictory cognitive capacities among substance-abusing patients with schizophrenia: a meta-analysis. Schizophr. Res.100(1–3), 242–251 (2008).
  • Andréasson S, Allebeck P, Engström A, Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet2(8574), 1483–1486 (1987).
  • Zammit S, Allebeck P, Andreasson S, Lundberg I, Lewis G. Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ325(7374), 1199 (2002).
  • Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ325(7374), 1212–1213 (2002).
  • van Os J, Bak M, Hanssen M, Bijl RV, de Graaf R, Verdoux H. Cannabis use and psychosis: a longitudinal population-based study. Am. J. Epidemiol.156(4), 319–327 (2002).
  • Viveros MP, Llorente R, Moreno E, Marco EM. Behavioural and neuroendocrine effects of cannabinoids in critical developmental periods. Behav. Pharmacol.16(5–6), 353–362 (2005).
  • Arendt M, Rosenberg R, Foldager L, Perto G, Munk-Jørgensen P. Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases. Br. J. Psychiatry187(6), 510–515 (2005).
  • Veen ND, Selten JP, van der Tweel I, Feller WG, Hoek HW, Kahn RS. Cannabis use and age at onset of schizophrenia. Am. J. Psychiatry161(3), 501–506 (2004).
  • Henquet C, Krabbendam L, Spauwen J et al. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ330(7481), 11 (2005).
  • Fergusson DM, Horwood LJ, Swain-Campbell NR. Cannabis dependence and psychotic symptoms in young people. Psychol. Med.33(1), 15–21 (2003).
  • Fergusson DM, Horwood LJ, Ridder EM. Tests of causal linkages between cannabis use and psychotic symptoms. Addiction100(3), 354–366 (2005).
  • Weiser M, Knobler HY, Noy S, Kaplan Z. Clinical characteristics of adolescents later hospitalized for schizophrenia. Am. J. Med. Genet.114(8), 949–955 (2002).
  • Smit F, Bolier L, Cuijpers P. Cannabis use and the risk of later schizophrenia: a review. Addiction99(4), 425–430 (2004).
  • Meltzer HY, Stahl SM. The dopamine hypothesis of schizophrenia: a review. Schizophr. Bull.2(1), 19–76 (1976).
  • Brunette MF, Drake RE, Xie H, McHugo GJ, Green AI. Clozapine use and relapses of substance use disorder among patients with co-occurring schizophrenia and substance use disorders. Schizophr. Bull.32(4), 637–643 (2006).
  • Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr. Bull.26(2), 441–449 (2000).
  • San L, Arranz B, Martinez-Raga J. Antipsychotic drug treatment of schizophrenic patients with substance abuse disorders. Eur. Addict. Res.13(4), 230–243 (2007).
  • Sundram S, Copolov D, Dean B. Clozapine decreases [3H] CP 55940 binding to the cannabinoid 1 receptor in the rat nucleus accumbens. Naunyn Schmiedebergs Arch. Pharmacol.371(5), 428–433 (2005).
  • Voruganti LN, Slomka P, Zabel P, Mattar A, Awad AG. Cannabis induced dopamine release: an in-vivo SPECT study. Psychiatry Res.107(3), 173–177 (2001).
  • Bowers MB, Kantrowitz JT. Elevated plasma dopamine metabolites in cannabis psychosis. Am. J. Psychiatry164(10), 1615–1616 (2007).
  • Markianos M, Vakis A. Effects of acute cannabis use on urinary neurotransmitter metabolites and cyclic nucleotides in man. Drug. Alcohol Depend.14(2), 175–178 (1984).
  • Giuffrida A, Parsons LH, Kerr TM, Rodríguez de Fonseca F, Navarro M, Piomelli D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat. Neurosci.2(4), 358–363 (1999).
  • Cadogan AK, Alexander SP, Boyd EA, Kendall DA. Influence of cannabinoids on electrically evoked dopamine release and cyclic AMP generation in the rat striatum. J. Neurochem.69(3), 1131–1137 (1997).
  • Gessa GL, Melis M, Muntoni AL, Diana M. Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. Eur. J. Pharmacol.341(1), 39–44 (1998).
  • Mailleux P, Vanderhaeghen JJ. Dopaminergic regulation of cannabinoid receptor mRNA levels in the rat caudate-putamen: an in situ hybridization study. J. Neurochem.61(5), 1705–1712 (1993).
  • Bonnin A, de Miguel R, Castro JG, Ramos JA, Fernandez-Ruiz JJ. Effects of perinatal exposure to Δ9-tetrahydrocannabinol on the fetal and early postnatal development of tyrosine hydroxylase-containing neurons in rat brain. J. Mol. Neurosci.7(4), 291–308 (1996).
  • Dean B, Bradbury R, Copolov DL. Cannabis-sensitive dopaminergic markers in postmortem central nervous system: changes in schizophrenia. Biol. Psychiatry53(7), 585–592 (2003).
  • Tzavara ET, Li DL, Moutsimilli L et al. Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications. Biol. Psychiatry59(6), 508–515 (2006).
  • D’Souza DC, Perry E, MacDougall L et al. The psychotomimetic effects of intravenous Δ-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology29(8), 1558–1572 (2004).
  • D’Souza DC, Ranganathan M, Braley G et al. Blunted psychotomimetic and amnestic effects of Δ-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology198(4), 587–603 (2008).
  • D’Souza DC, Braley G, Blaise R et al. Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans. Psychopharmacology (Berl.) (2008) (Epub ahead of print).
  • Ranganathan M, D’Souza DC. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berl.)188(4), 425–444 (2006).
  • Emrich HM, Leweke FM, Schneider U. Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system. Pharmacol. Biochem. Behav.56(4), 803–807 (1997).
  • Schneider U, Leweke FM, Sternemann U, Weber MM, Emrich HM. Visual 3D illusion: a systems-theoretical approach to psychosis. Eur. Arch. Psychiatry Clin. Neurosci.246(5), 256–260 (1996).
  • Sternemann U, Schneider U, Leweke FM, Bevilacqua CM, Dietrich DE, Emrich HM. Pro-psychotic change of binocular depth inversion by sleep deprivation. Nervenarzt68(7), 593–596 (1997).
  • Schneider U, Leweke FM, Niemcyzk W, Sternemann U, Bevilacqua M, Emrich HM. Impaired binocular depth inversion in patients with alcohol withdrawal. J. Psychiatr. Res.30(6), 469–474 (1996).
  • Koethe D, Gerth CW, Neatby MA et al. Disturbances of visual information processing in early states of psychosis and experimental Δ-9-tetrahydrocannabinol altered states of consciousness. Schizophr. Res.88(1–3), 142–150 (2006).
  • Schneider U, Borsutzky M, Seifert J et al. Reduced binocular depth inversion in schizophrenic patients. Schizophr. Res.53(1–2), 101–108 (2002).
  • Semple DM, Ramsden F, McIntosh AM. Reduced binocular depth inversion in regular cannabis users. Pharmacol. Biochem. Behav.75(4), 789–793 (2003).
  • Leweke FM, Schneider U, Radwan M, Schmidt E, Emrich HM. Different effects of nabilone and cannabidiol on binocular depth inversion in Man. Pharmacol. Biochem. Behav.66(1), 175–181 (2000).
  • Zuardi AW, Morais SL, Guimarães FS, Mechoulam R. Antipsychotic effect of cannabidiol. J. Clin. Psychiatry56(10), 485–486 (1995).
  • Gray JA, Rawlins JNP. Comparator and buffer memory: an attempt to integrate two models of hippocamaö functions. In: The Hippocampus. Isaacson RL, Pribram KH (Eds), Plenum Press, NY, USA, 159–201 (1986).
  • Frith CD, Done DJ. Experiences of alien control in schizophrenia reflect a disorder in the central monitoring of action. Psychol. Med.19(2), 359–363 (1989).
  • Malenka RC, Angel RW, Hampton B, Berger PA. Impaired central error-correcting behavior in schizophrenia. Arch. Gen. Psychiatry39(1), 101–107 (1982).
  • Emrich HM. A three-component-system hypothesis of psychosis. Impairment of binocular depth inversion as an indicator of a functional dysequilibrium. Br. J. Psychiatry Suppl.5, 37–39 (1989).
  • Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport10(8), 1665–1669 (1999).
  • Giuffrida A, Leweke FM, Gerth CW et al. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology29(11), 2108–2114 (2004).
  • Leweke FM, Giuffrida A, Koethe D et al. Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophr. Res.94(1–3), 29–36 (2007).
  • De Marchi N, De Petrocellis L, Orlando P, Daniele F, Fezza F, Di Marzo V. Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis.2, 5 (2003).
  • Yao JK, van Kammen DP, Reddy RD et al. Elevated endocannabinoids in plasma from patients with schizophrenia. Biol. Psychiatry51, 64S–65S (2002).
  • Mailleux P, Vanderhaeghen JJ. Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization histochemistry. Neuroscience48(3), 655–668 (1992).
  • Dean B, Sundram S, Bradbury R, Scarr E, Copolov D. Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience103(1), 9–15 (2001).
  • Zavitsanou K, Garrick T, Huang XF. Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry28(2), 355–360 (2004).
  • Koethe D, Llenos IC, Dulay JR et al. Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression. J. Neural. Transm.114(8), 1055–1063 (2007).
  • Newell KA, Zavitsanou K, Jew SK, Huang XF. Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry31(1), 225–233 (2007).
  • Newell KA, Zavitsanou K, Huang XF. Ionotropic glutamate receptor binding in the posterior cingulate cortex in schizophrenia patients. Neuroreport16(12), 1363–1367 (2005).
  • Newell KA, Deng C, Huang XF. Increased cannabinoid receptor density in the posterior cingulate cortex in schizophrenia. Exp. Brain Res.172(4), 556–560 (2006).
  • Berding G, Schneider U, Gielow P et al. Feasibility of central cannabinoid CB1 receptor imaging with [124I]AM281 PET demonstrated in a schizophrenic patient. Psychiatry Res.147(2–3), 249–256 (2006).
  • Chua SE, Cheung C, Cheung V et al. Cerebral grey, white matter and CSF in never-medicated, first-episode schizophrenia. Schizophr. Res.89(1–3), 12–21 (2007).
  • Cahn W, van Haren NE, Hulshoff Pol HE et al. Brain volume changes in the first year of illness and 5-year outcome of schizophrenia. Br. J. Psychiatry189(4), 381–382 (2006).
  • Matochik JA, Eldreth DA, Cadet JL, Bolla KI. Altered brain tissue composition in heavy marijuana users. Drug Alcohol Depend.77(1), 23–30 (2005).
  • Block RI, O’Leary DS, Ehrhardt JC et al. Effects of frequent marijuana use on brain tissue volume and composition. Neuroreport11(3), 491–496 (2000).
  • Cahn W, Hulshoff Pol HE, Caspers E, van Haren NE, Schnack HG, Kahn RS. Cannabis and brain morphology in recent-onset schizophrenia. Schizophr. Res.67(2–3), 305–307 (2004).
  • Bangalore SS, Prasad KM, Montrose DM, Goradia DD, Diwadkar VA, Keshavan MS. Cannabis use and brain structural alterations in first episode schizophrenia – a region of interest, voxel based morphometric study. Schizophr. Res.99(1–3), 1–6 (2008).
  • Szeszko PR, Robinson DG, Sevy S et al. Anterior cingulate grey-matter deficits and cannabis use in first-episode schizophrenia. Br. J. Psychiatry190(3), 230–236 (2007).
  • Rais M, Cahn W, Van Haren N et al. Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. Am. J. Psychiatry165(4), 490–496 (2008).
  • Broome MR, Woolley JB, Tabraham P et al. What causes the onset of psychosis? Schizophr. Res.79(1), 23–34 (2005).
  • Lewis CM, Levinson DF, Wise LH et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am. J. Hum. Genet.73(1), 34–48 (2003).
  • Ujike H, Takaki M, Nakata K et al. CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia. Mol. Psychiatry7(5), 515–518 (2002).
  • Gadzicki D, Müller-Vahl K, Stuhrmann M. A frequent polymorphism in the coding exon of the human cannabinoid receptor (CNR1) gene. Mol. Cell Probes13(4), 321–323 (1999).
  • Martínez-Gras I, Hoenicka J, Ponce G et al. (AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population. Eur. Arch. Psychiatry Clin. Neurosci.256(7), 437–441 (2006).
  • Leroy S, Griffon N, Bourdel MC, Olié JP, Poirier MF, Krebs MO. Schizophrenia and the cannabinoid receptor type 1 (CB1): association study using a single-base polymorphism in coding exon 1. Am. J. Med. Genet.105(8), 749–752 (2001).
  • Tsai SJ, Wang YC, Hong CJ. Association study of a cannabinoid receptor gene (CNR1) polymorphism and schizophrenia. Psychiatr. Genet.10(3), 149–151 (2000).
  • Zammit S, Spurlock G, Williams H et al. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br. J. Psychiatry191(5), 402–407 (2007).
  • Henquet C, Rosa A, Krabbendam L et al. An experimental study of catechol-O-methyltransferase Val158Met moderation of Δ-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology31(12), 2748–2757 (2006).
  • Caspi A, Moffitt TE, Cannon M et al. 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. Psychiatry57(10), 1117–1127 (2005).
  • Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by Δ 9-THC in normal subjects. Psychopharmacology (Berl.)76(3), 245–250 (1982).
  • Zuardi AW, Rodrigues JA, Cunha JM. Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology (Berl.)104(2), 260–264 (1991).
  • Zuardi AW, Morais SL, Guimarães FS, Mechoulam R. Antipsychotic effect of cannabidiol. J. Clin. Psychiatry56(10), 485–486 (1995).
  • Zuardi AW, Hallak JE, Dursun SM et al. Cannabidiol monotherapy for treatment-resistant schizophrenia. J. Psychopharmacol.20(5), 683–686 (2006).
  • Zuardi AW, Guimarães FS, Moreira AC. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers. Braz. J. Med. Biol. Res.26(2), 213–217 (1993).
  • Consroe P, Laguna J, Allender J et al. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol. Biochem. Behav.40(3), 701–708 (1991).
  • Mechoulam R, Hanus L. Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects. Chem. Phys. Lipids121(1–2), 35–43 (2002).
  • Bisogno T, Hanus L, De Petrocellis L et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol.134(4), 845–852 (2001).
  • Meltzer HY, Arvanitis L, Bauer D, Rein W; Meta-Trial Study Group. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am. J. Psychiatry161(6), 975–984 (2004).
  • Madsen MV, Peacock L, Werge T, Andersen MB. Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on dHamphetamine-induced behaviours in Cebus monkeys. J. Psychopharmacol.20(5), 622–628 (2006).
  • Morgan CJ, Curran HV. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br. J. Psychiatry192, 306–307 (2008).

Website

  • Leweke FM, Koethe D, Gerth CW et al. Cannabidiol as an antipsychotic. A double-blind, controlled clinical trial on cannabidiol vs. amusilpride in acute schizophrenia. Presented at: 2005 IACM 3rd Conference on Cannabinoids in Medicine. Leiden, The Netherlands, 9–10 September 2005. www.cannabis-med.org/english/nav/home-conference.htm

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.