Epidemiological studies have shown that the association between cannabis and psychosis is robust and consistent across different samples, with compelling evidence for a dose-response relationship. Because longitudinal work indicates that cannabis use precedes psychotic symptoms, it seems reasonable to assume a causal relationship. However, more work is needed to address the possibility of gene-environment correlation (for example, genetic risk for psychosis causing onset of cannabis use). Moreover, knowledge about underlying biological mechanisms linking cannabis use and psychosis is still relatively limited. In order to understand how cannabis use may lead to an increased risk for psychosis, in the present article we () review the epidemiological, neurobiological, and genetic evidence linking cannabinoids and psychosis, () assess the quality of the evidence, and finally () try to integrate the most robust findings into a neurodevelopmental model of cannabis-induced psychosis and identify the gaps in knowledge that are in need of further investigation.


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Literature Cited

  1. Alemany S, Arias B, Fatjo-Vilas M, Villa H, Moya J. et al. 2014. Psychosis-inducing effects of cannabis are related to both childhood abuse and COMT genotypes. Acta Psychiatr. Scand. 12954–62 [Google Scholar]
  2. Anavi-Goffer S, Baillie G, Irving AJ, Gertsch J, Greig IR. et al. 2012. Modulation of L-alpha-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. J. Biol. Chem. 287:91–104 [Google Scholar]
  3. Arnold JC, Boucher AA, Karl T. 2012. The yin and yang of cannabis-induced psychosis: the actions of Δ(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia. Curr. Pharm. Des. 18:5113–30 [Google Scholar]
  4. 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 41:1067–74 [Google Scholar]
  5. Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. 2002. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 325:1212–13 [Google Scholar]
  6. Azad SC, Kurz J, Marsicano G, Lutz B, Zieglgansberger W, Rammes G. 2008. Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala. Learn. Mem. 15:143–52 [Google Scholar]
  7. Bacci A, Huguenard JR, Prince DA. 2004. Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 431:312–16 [Google Scholar]
  8. Barkus E, Morrison PD, Vuletic D, Dickson JC, Ell PJ. et al. 2011. Does intravenous Δ9-tetrahydrocannabinol increase dopamine release? A SPET study. J. Psychopharmacol. 25:1462–68 [Google Scholar]
  9. Batalla A, Soriano-Mas C, Lopez-Sola M, Torrens M, Crippa JA. et al. 2013. Modulation of brain structure by catechol-o-methyltransferase Val(158)Met polymorphism in chronic cannabis users. Addict. Biol. In press. doi:10.1111/adb.12027 [Google Scholar]
  10. Battisti RA, Roodenrys S, Johnstone SJ, Pesa N, Hermens DF, Solowij N. 2010. Chronic cannabis users show altered neurophysiological functioning on Stroop task conflict resolution. Psychopharmacology 212:613–24 [Google Scholar]
  11. Behan A, Hryniewiecka M, O'Tuathaigh CM, Kinsella A, Cannon M. et al. 2012. Chronic adolescent exposure to delta-9-tetrahydrocannabinol in COMT mutant mice: impact on indices of dopaminergic, endocannabinoid and GABAergic pathways. Neuropsychopharmacology 37:1773–83 [Google Scholar]
  12. Bhattacharyya S, Crippa JA, Allen P, Martin-Santos R, Borgwardt S. et al. 2012. Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. Arch. Gen. Psychiatry 69:27–36 [Google Scholar]
  13. Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S. et al. 2010. Opposite effects of Δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 35:764–74 [Google Scholar]
  14. Bloomfield MA, Morgan CJ, Egerton A, Kapur S, Curran HV, Howes OD. 2013. Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms. Biol. Psychiatry. In press [Google Scholar]
  15. Borgwardt SJ, Allen P, Bhattacharyya S, Fusar-Poli P, Crippa JA. et al. 2008. Neural basis of Δ-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition. Biol. Psychiatry 64:966–73 [Google Scholar]
  16. Bossong MG, Niesink RJ. 2010. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog. Neurobiol. 92370–85 [Google Scholar]
  17. Bossong MG, van Berckel BN, Boellaard R, Zuurman L, Schuit RC. et al. 2009. Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology 34:759–66 [Google Scholar]
  18. Broyd SJ, Greenwood LM, Croft RJ, Dalecki A, Todd J. et al. 2013. Chronic effects of cannabis on sensory gating. Int. J. Psychophysiol. 89:381–89 [Google Scholar]
  19. Caspi A, Moffitt TE, Cannon M, McClay J, Murray R. 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 [Google Scholar]
  20. Castillo PE, Younts TJ, Chavez AE, Hashimotodani Y. 2012. Endocannabinoid signaling and synaptic function. Neuron 76:70–81 [Google Scholar]
  21. Chavez AE, Chiu CQ, Castillo PE. 2010. TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat. Neurosci. 13:1511–18 [Google Scholar]
  22. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M. et al. 2004. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am. J. Hum. Genet. 75:807–21 [Google Scholar]
  23. Chevaleyre V, Takahashi KA, Castillo PE. 2006. Endocannabinoid-mediated synaptic plasticity in the CNS. Annu. Rev. Neurosci. 29:37–76 [Google Scholar]
  24. Costas J, Sanjuan J, Ramos-Rios R, Paz E, Agra S. et al. 2011. Interaction between COMT haplotypes and cannabis in schizophrenia: a case-only study in two samples from Spain. Schizophr. Res. 127:22–27 [Google Scholar]
  25. Cougnard A, Marcelis M, Myin-Germeys I, De Graaf R, Vollebergh W. et al. 2007. Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness-persistence model. Psychol. Med. 37:513–27 [Google Scholar]
  26. Smoller JW, Craddock N, Kendler KS, Lee PH. Cross-Disord. Group Psychiatr. Genomics Consort. et al. 2013. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381:1371–79 [Google Scholar]
  27. D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T. et al. 2004. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29:1558–72 [Google Scholar]
  28. Decoster J, Van Os J, Myin-Germeys I, De Hert M, van Winkel R. 2012. Genetic variation underlying psychosis-inducing effects of cannabis: critical review and future directions. Curr. Pharm. Des. 18:5015–23 [Google Scholar]
  29. Demirakca T, Sartorius A, Ende G, Meyer N, Welzel H. et al. 2011. Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol. Drug Alcohol Depend. 114:242–45 [Google Scholar]
  30. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA. et al. 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–49 [Google Scholar]
  31. Di Forti M, Iyegbe C, Sallis H, Kolliakou A, Falcone A. et al. 2012. Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biol. Psychiatry 72:811–16 [Google Scholar]
  32. Dominguez MD, Wichers M, Lieb R, Wittchen HU, van Os J. 2011. Evidence that onset of clinical psychosis is an outcome of progressively more persistent subclinical psychotic experiences: an 8-year cohort study. Schizophr. Bull. 37:84–93 [Google Scholar]
  33. Duncan LE, Keller MC. 2011. A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. Am. J. Psychiatry 168:1041–49 [Google Scholar]
  34. Egerton A, Chaddock CA, Winton-Brown TT, Bloomfield MA, Bhattacharyya S. et al. 2013. Presynaptic striatal dopamine dysfunction in people at ultra-high risk for psychosis: findings in a second cohort. Biol. Psychiatry 74:106–12 [Google Scholar]
  35. Ehrenreich H, Rinn T, Kunert HJ, Moeller MR, Poser W. et al. 1999. Specific attentional dysfunction in adults following early start of cannabis use. Psychopharmacology 142:295–301 [Google Scholar]
  36. El Khoury MA, Gorgievski V, Moutsimilli L, Giros B, Tzavara ET. 2012. Interactions between the cannabinoid and dopaminergic systems: evidence from animal studies. Prog. Neuropsychopharmacol. Biol. Psychiatry 38:36–50 [Google Scholar]
  37. Englund A, Morrison PD, Nottage J, Hague D, Kane F. et al. 2013. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J. Psychopharmacol. 27:19–27 [Google Scholar]
  38. Estrada G, Fatjó-Vilas M, Muñoz MJ, Pulido G, Miñano MJ. et al. 2011. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Acta Psychiatr. Scand. 123:485–92 [Google Scholar]
  39. Ferdinand RF, Sondeijker F, van der Ende J, Selten JP, Huizink A, Verhulst FC. 2005. Cannabis use predicts future psychotic symptoms, and vice versa. Addiction 100:612–18 [Google Scholar]
  40. Fergusson DM, Horwood LJ, Swain-Campbell NR. 2003. Cannabis dependence and psychotic symptoms in young people. Psychol. Med. 33:15–21 [Google Scholar]
  41. Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A. et al. 2010. Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol. Int. J. Neuropsychopharmacol. 13:421–32 [Google Scholar]
  42. Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P. et al. 2009. Distinct effects of Δ9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch. Gen. Psychiatry 66:95–105 [Google Scholar]
  43. Genetic Risk Outcome Psychos. (GROUP) Investig 2011. Evidence that familial liability for psychosis is expressed as differential sensitivity to cannabis: an analysis of patient-sibling and sibling-control pairs. Arch. Gen. Psychiatry 68:138–47 [Google Scholar]
  44. Grueter BA, Brasnjo G, Malenka RC. 2010. Postsynaptic TRPV1 triggers cell type–specific long-term depression in the nucleus accumbens. Nat. Neurosci. 13:1519–25 [Google Scholar]
  45. Gutiérrez B, Rivera M, Obel L, McKenney K, Martínez-Leal R. et al. 2009. Variability in the COMT gene and modification of the risk of schizophrenia conferred by cannabis consumption. Rev. Psiquiatr. Salud Ment. 2:89–94 [Google Scholar]
  46. Habets P, Marcelis M, Gronenschild E, Drukker M, van Os J. 2011. Reduced cortical thickness as an outcome of differential sensitivity to environmental risks in schizophrenia. Biol. Psychiatry 69:487–94 [Google Scholar]
  47. Hall W, Solowij N. 1998. Adverse effects of cannabis. Lancet 352:1611–16 [Google Scholar]
  48. Harley M, Kelleher I, Clarke M, Lynch F, Arseneault L. et al. 2010. Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence. Psychol. Med. 40:1627–34 [Google Scholar]
  49. Henquet C, Krabbendam L, Spauwen J, Kaplan C, Lieb R. et al. 2005a. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ 330:11–14 [Google Scholar]
  50. Henquet C, Murray R, Linszen D, van Os J. 2005b. The environment and schizophrenia: the role of cannabis use. Schizophr. Bull. 31:608–12 [Google Scholar]
  51. Henquet C, Rosa A, Delespaul P, Papiol S, Fananas L. et al. 2009. COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of “switching on” hallucinations in the flow of daily life. Acta Psychiatr. Scand. 119:156–60 [Google Scholar]
  52. Henquet C, Rosa A, Krabbendam L, Papiol S, Fananas L. et al. 2006. An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31:2748–57 [Google Scholar]
  53. Hoffman AF, Oz M, Yang R, Lichtman AH, Lupica CR. 2007. Opposing actions of chronic Δ9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation. Learn. Mem. 14:63–74 [Google Scholar]
  54. Hollis C, Groom MJ, Das D, Calton T, Bates AT. et al. 2008. Different psychological effects of cannabis use in adolescents at genetic high risk for schizophrenia and with attention deficit/hyperactivity disorder (ADHD). Schizophr. Res. 105:216–23 [Google Scholar]
  55. Houston JE, Murphy J, Adamson G, Stringer M, Shevlin M. 2008. Childhood sexual abuse, early cannabis use, and psychosis: testing an interaction model based on the National Comorbidity Survey. Schizophr. Bull. 34:580–85 [Google Scholar]
  56. Houston JE, Murphy J, Shevlin M, Adamson G. 2011. Cannabis use and psychosis: re-visiting the role of childhood trauma. Psychol. Med. 41:2339–48 [Google Scholar]
  57. Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M. et al. 2012. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch. Gen. Psychiatry 69:776–86 [Google Scholar]
  58. Howlett AC, Reggio PH, Childers SR, Hampson RE, Ulloa NM, Deutsch DG. 2011. Endocannabinoid tone versus constitutive activity of cannabinoid receptors. Br. J. Pharmacol. 163:1329–43 [Google Scholar]
  59. Kantrowitz JT, Nolan KA, Sen S, Simen A, Lachman HM, Bowers M. 2009. Adolescent cannabis use, psychosis and catechol-O-methyltransferase genotype in African Americans and Caucasians. Psychiatr. Q. 80:213–18 [Google Scholar]
  60. Klugmann M, Klippenstein V, Leweke FM, Spanagel R, Schneider M. 2011. Cannabinoid exposure in pubertal rats increases spontaneous ethanol consumption and NMDA receptor associated protein levels. Int. J. Neuropsychopharmacol. 14:505–17 [Google Scholar]
  61. Konings M, Bak M, Hanssen M, van Os J, Krabbendam L. 2006. Validity and reliability of the CAPE: a self-report instrument for the measurement of psychotic experiences in the general population. Acta Psychiatr. Scand. 114:55–61 [Google Scholar]
  62. Konings M, Henquet C, Maharajh HD, Hutchinson G, Van Os J. 2008. Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad. Acta Psychiatr. Scand. 118:209–13 [Google Scholar]
  63. Konings M, Stefanis N, Kuepper R, de Graaf R, ten Have M. et al. 2012. Replication in two independent population-based samples that childhood maltreatment and cannabis use synergistically impact on psychosis risk. Psychol. Med. 42:149–59 [Google Scholar]
  64. Kuepper R, Ceccarini J, Lataster J, Van Os J, Van Kroonenburgh M. et al. 2013. Delta-9-tetrahydrocannabinol-induced dopamine release as a function of psychosis risk:18F-fallypride positron emission tomography study. PLoS ONE 8:e70378 [Google Scholar]
  65. Kuepper R, Henquet C, Lieb R, Wittchen HU, van Os J. 2011a. Non-replication of interaction between cannabis use and trauma in predicting psychosis. Schizophr. Res. 131:262–63 [Google Scholar]
  66. Kuepper R, Morrison PD, van Os J, Murray RM, Kenis G, Henquet C. 2010. Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines. Schizophr. Res. 121:107–17 [Google Scholar]
  67. Kuepper R, van Os J, Lieb R, Wittchen HU, Henquet C. 2011b. Do cannabis and urbanicity co-participate in causing psychosis? Evidence from a 10-year follow-up cohort study. Psychol. Med. 41:2121–9 [Google Scholar]
  68. Kuepper R, van Os J, Lieb R, Wittchen HU, Hofler M, Henquet C. 2011c. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ 342:d738 [Google Scholar]
  69. Littleton JM, MacLean KI, Brownlee G. 1976. Proceedings: alterations in dopamine uptake in rat corpus striatum induced by combinations of stress and delta8-tetrahydrocannabinol (delta8-THC). Br. J. Pharmacol. 56:370P [Google Scholar]
  70. Lopez-Moreno JA, Gonzalez-Cuevas G, Moreno G, Navarro M. 2008. The pharmacology of the endocannabinoid system: functional and structural interactions with other neurotransmitter systems and their repercussions in behavioral addiction. Addict. Biol. 13:160–87 [Google Scholar]
  71. Lundqvist T. 2005. Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacol. Biochem. Behav. 81:319–30 [Google Scholar]
  72. Mackie K. 2005. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb. Exp. Pharmacol. 168:299–325 [Google Scholar]
  73. MacLean KI, Littleton JM. 1977. Environmental stress as a factor in the response of rat brain catecholamine metabolism to delta8-tetrahydrocannabinol. Eur. J. Pharmacol. 41:171–82 [Google Scholar]
  74. Marinelli S, Pacioni S, Cannich A, Marsicano G, Bacci A. 2009. Self-modulation of neocortical pyramidal neurons by endocannabinoids. Nat. Neurosci. 12:1488–90 [Google Scholar]
  75. Martin-Santos R, Fagundo AB, Crippa JA, Atakan Z, Bhattacharyya S. et al. 2010. Neuroimaging in cannabis use: a systematic review of the literature. Psychol. Med. 40:383–98 [Google Scholar]
  76. Mato S, Chevaleyre V, Robbe D, Pazos A, Castillo PE, Manzoni OJ. 2004. A single in-vivo exposure to delta 9 THC blocks endocannabinoid-mediated synaptic plasticity. Nat. Neurosci. 7:585–86 [Google Scholar]
  77. McGrath J, Welham J, Scott J, Varghese D, Degenhardt L. et al. 2010. Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults. Arch. Gen. Psychiatry 67:440–47 [Google Scholar]
  78. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE. et al. 1995. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50:83–90 [Google Scholar]
  79. Mechoulam R, Parker LA, Gallily R. 2002. Cannabidiol: an overview of some pharmacological aspects. J. Clin. Pharmacol. 42:11–19S [Google Scholar]
  80. Meier MH, Caspi A, Ambler A, Harrington H, Houts R. et al. 2012. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc. Natl. Acad. Sci. USA 109:E2657–64 [Google Scholar]
  81. Mizrahi R, Suridjan I, Kenk M, George TP, Wilson A. et al. 2013. Dopamine response to psychosocial stress in chronic cannabis users: a PET study with [(11)C]-(+)-PHNO. Neuropsychopharmacology 38:673–82 [Google Scholar]
  82. Mokler DJ, Robinson SE, Johnson JH, Hong JS, Rosecrans JA. 1987. Neonatal administration of delta-9-tetrahydrocannabinol (THC) alters the neurochemical response to stress in the adult Fischer-344 rat. Neurotoxicol. Teratol. 9:321–27 [Google Scholar]
  83. Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB. et al. 2007. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370:319–28 [Google Scholar]
  84. Morgan CJ, Curran HV. 2008. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br. J. Psychiatry 192:306–7 [Google Scholar]
  85. Morgan CJ, Gardener C, Schafer G, Swan S, Demarchi C. et al. 2012. Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being. Psychol. Med. 42:391–400 [Google Scholar]
  86. Morgan CJ, Schafer G, Freeman TP, Curran HV. 2010. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study [corrected]. Br. J. Psychiatry 197:285–90 [Google Scholar]
  87. Morrison PD, Murray RM. 2009. From real-world events to psychosis: the emerging neuropharmacology of delusions. Schizophr. Bull. 35:668–74 [Google Scholar]
  88. Morrison PD, Stone JM. 2011. Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation. Hum. Psychopharmacol. 26:77–80 [Google Scholar]
  89. Morrison PD, Zois V, McKeown DA, Lee TD, Holt DW. et al. 2009. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol. Med. 39:1607–16 [Google Scholar]
  90. Murphy J, Houston JE, Shevlin M, Adamson G. 2013. Childhood sexual trauma, cannabis use and psychosis: statistically controlling for pre-trauma psychosis and psychopathology. Soc. Psychiatry Psychiatr. Epidemiol. 48:853–61 [Google Scholar]
  91. Murray RM, Morrison PD, Henquet C, Di Forti M. 2007. Cannabis, the mind and society: the hash realities. Nat. Rev. 8:885–95 [Google Scholar]
  92. Ohno-Shosaku T, Tanimura A, Hashimotodani Y, Kano M. 2012. Endocannabinoids and retrograde modulation of synaptic transmission. Neuroscientist 18:119–32 [Google Scholar]
  93. O'Tuathaigh CM, Clarke G, Walsh JJ, Desbonnet L, Petit E. et al. 2012. Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes. Int. J. Neuropsychopharmacol. 15:1331–42 [Google Scholar]
  94. O'Tuathaigh CM, Hryniewiecka M, Behan A, Tighe O, Coughlan C. et al. 2010. Chronic adolescent exposure to delta-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes. Neuropsychopharmacology 35:2262–73 [Google Scholar]
  95. Pelayo-Teran JM, Perez-Iglesias R, Mata I, Carrasco-Marin E, Vazquez-Barquero JL, Crespo-Facorro B. 2010. Catechol-O-methyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications. Psychiatr. Res. 179:291–96 [Google Scholar]
  96. Pertwee RG. 1997. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther. 74:129–80 [Google Scholar]
  97. Pertwee RG. 2008. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br. J. Pharmacol. 153:199–215 [Google Scholar]
  98. Pertwee RG. 2010. Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr. Med. Chem. 17:1360–81 [Google Scholar]
  99. Pistis M, Perra S, Pillolla G, Melis M, Muntoni AL, Gessa GL. 2004. Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol. Psychiatry 56:86–94 [Google Scholar]
  100. Pope HG Jr, Gruber AJ, Hudson JI, Cohane G, Huestis MA, Yurgelun-Todd D. 2003. Early-onset cannabis use and cognitive deficits: What is the nature of the association?. Drug Alcohol Depend. 69:303–10 [Google Scholar]
  101. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC. et al. 2009. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460:748–52 [Google Scholar]
  102. Rabin RA, Zakzanis KK, George TP. 2011. The effects of cannabis use on neurocognition in schizophrenia: a meta-analysis. Schizophr. Res. 128:111–16 [Google Scholar]
  103. Ranganathan M, D'Souza DC. 2006. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology 188:425–44 [Google Scholar]
  104. Realini N, Rubino T, Parolaro D. 2009. Neurobiological alterations at adult age triggered by adolescent exposure to cannabinoids. Pharmacol. Res. 60:132–38 [Google Scholar]
  105. Rubino T, Realini N, Braida D, Guidi S, Capurro V. et al. 2009. Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus 19:763–72 [Google Scholar]
  106. Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO. et al. 2007. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol. 152:1092–101 [Google Scholar]
  107. Schneider M, Drews E, Koch M. 2005. Behavioral effects in adult rats of chronic prepubertal treatment with the cannabinoid receptor agonist WIN 55,212–2. Behav. Pharmacol. 16:447–54 [Google Scholar]
  108. Schneider M, Koch M. 2003. Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology 28:1760–69 [Google Scholar]
  109. Schneider M, Koch M. 2007. The effect of chronic peripubertal cannabinoid treatment on deficient object recognition memory in rats after neonatal mPFC lesion. Eur. Neuropsychopharmacol. 17:180–86 [Google Scholar]
  110. Schneider M, Schomig E, Leweke FM. 2008. Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats. Addict. Biol. 13:345–57 [Google Scholar]
  111. Schubart CD, Boks MP, Breetvelt EJ, van Gastel WA, Groenwold RH. et al. 2011a. Association between cannabis and psychiatric hospitalization. Acta Psychiatr. Scand. 123:368–75 [Google Scholar]
  112. Schubart CD, Sommer IE, van Gastel WA, Goetgebuer RL, Kahn RS, Boks MP. 2011b. Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr. Res. 130:216–21 [Google Scholar]
  113. Smith MJ, Barch DM, Wolf T, Mamah D, Csernansky JG. 2008. Elevated rates of substance use disorders in non-psychotic siblings of individuals with schizophrenia. Schizophr. Res. 106:294–99 [Google Scholar]
  114. Solowij N. 1995. Do cognitive impairments recover following cessation of cannabis use?. Life Sci. 56:2119–26 [Google Scholar]
  115. Solowij N, Battisti R. 2008. The chronic effects of cannabis on memory in humans: a review. Curr. Drug Abuse Rev. 1:81–98 [Google Scholar]
  116. Solowij N, Stephens RS, Roffman RA, Babor T, Kadden R. et al. 2002. Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA 287:1123–31 [Google Scholar]
  117. Solowij N, Walterfang M, Lubman DI, Whittle S, Lorenzetti V. et al. 2013. Alteration to hippocampal shape in cannabis users with and without schizophrenia. Schizophr. Res. 143:179–84 [Google Scholar]
  118. Solowij N, Yücel M, Respondek C, Whittle S, Lindsay E. et al. 2011. Cerebellar white-matter changes in cannabis users with and without schizophrenia. Psychol. Med. 41:2349–59 [Google Scholar]
  119. Stefanis NC, Delespaul P, Henquet C, Bakoula C, Stefanis CN, Van Os J. 2004. Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction 99:1333–41 [Google Scholar]
  120. Stokes PR, Egerton A, Watson B, Reid A, Breen G. et al. 2010. Significant decreases in frontal and temporal [11C]-raclopride binding after THC challenge. NeuroImage 52:1521–27 [Google Scholar]
  121. Stokes PR, Egerton A, Watson B, Reid A, Lappin J. et al. 2012. History of cannabis use is not associated with alterations in striatal dopamine D2/D3 receptor availability. J. Psychopharmacol. 26:144–49 [Google Scholar]
  122. Stokes PR, Mehta MA, Curran HV, Breen G, Grasby PM. 2009. Can recreational doses of THC produce significant dopamine release in the human striatum?. NeuroImage 48:186–90 [Google Scholar]
  123. Stowkowy J, Addington J. 2013. Predictors of a clinical high risk status among individuals with a family history of psychosis. Schizophr. Res. 147:281–86 [Google Scholar]
  124. Sullivan PF. 2007. Spurious genetic associations. Biol. Psychiatry 61:1121–26 [Google Scholar]
  125. Urban NB, Slifstein M, Thompson JL, Xu X, Girgis RR. et al. 2012. Dopamine release in chronic cannabis users: a [11c]raclopride positron emission tomography study. Biol. Psychiatry 71:677–83 [Google Scholar]
  126. van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. 2009. A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol. Med. 39:179–95 [Google Scholar]
  127. van Os J, Rutten BP, Poulton R. 2008. Gene-environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr. Bull. 34:1066–82 [Google Scholar]
  128. van Winkel R, Esquivel G, Kenis G, Wichers M, Collip D. et al. 2010. Genome-wide findings in schizophrenia and the role of gene-environment interplay. CNS Neurosci. Ther. 16:e185–92 [Google Scholar]
  129. van Winkel R, Genetic Risk Outcome Psychos. (GROUP) Investig 2011. Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up. Arch. Gen. Psychiatry 68:148–57 [Google Scholar]
  130. van Winkel R, Genetic Risk Outcome Psychos. (GROUP) Investig 2013. Family-based study examining moderation of familial correlation in psychosis-related experiences by the environment. Manuscr. submitted.
  131. van Winkel R, van Beveren JM. Genetic Risk Outcome Psychos. (GROUP) Investig 2011. AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder. Neuropsychopharmacology 36:2529–37 [Google Scholar]
  132. Veling W, Mackenbach JP, van Os J, Hoek HW. 2008. Cannabis use and genetic predisposition for schizophrenia: a case-control study. Psychol. Med. 38:1251–56 [Google Scholar]
  133. Verdejo-Garcia A, Beatriz Fagundo A, Cuenca A, Rodriguez J, Cuyas E. et al. 2013. COMT Val158Met and 5-HTTLPR genetic polymorphisms moderate executive control in cannabis users. Neuropsychopharmacology 38:1598–606 [Google Scholar]
  134. Vinkers C, Van Gastel WA, Schubart CD, Van Eijk K, Luykx J. et al. 2013. The effect of childhood maltreatment and cannabis use on adult psychotic symptoms is modified by the COMT Val158Met polymorphism. Schizophr. Res. 150:303–11 [Google Scholar]
  135. Voruganti LN, Slomka P, Zabel P, Mattar A, Awad AG. 2001. Cannabis induced dopamine release: an in-vivo SPECT study. Psychiatry Res. 107:173–77 [Google Scholar]
  136. Wegener N, Koch M. 2009. Behavioural disturbances and altered Fos protein expression in adult rats after chronic pubertal cannabinoid treatment. Brain Res. 1253:81–91 [Google Scholar]
  137. 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. J. Addict. Dis. 19:1–22 [Google Scholar]
  138. Winton-Brown TT, Allen P, Bhattacharyya S, Borgwardt SJ, Fusar-Poli P. et al. 2011. Modulation of auditory and visual processing by delta-9-tetrahydrocannabinol and cannabidiol: an FMRI study. Neuropsychopharmacology 36:1340–48 [Google Scholar]
  139. Yücel M, Bora E, Lubman DI, Solowij N, Brewer WJ. et al. 2012. 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. 38:316–30 [Google Scholar]
  140. Yücel M, Solowij N, Respondek C, Whittle S, Fornito A. et al. 2008. Regional brain abnormalities associated with long-term heavy cannabis use. Arch. Gen. Psychiatry 65:694–701 [Google Scholar]
  141. Zammit S, Owen M, Evans J, Heron J, Lewis G. 2011. Cannabis, COMT and psychotic experiences. Br. J. Psychiatry 199:380–85 [Google Scholar]
  142. Zammit S, Spurlock G, Williams H, Norton N, Williams N. et al. 2007. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br. J. Psychiatry 191:402–7 [Google Scholar]
  143. Zuardi AW, Crippa JA, Hallak JE, Bhattacharyya S, Atakan Z. et al. 2012. A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr. Pharm. Des. 18:5131–40 [Google Scholar]

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