Skip to main content Accessibility help

Cannabis use and genetic predisposition for schizophrenia: a case-control study

  • W. Veling (a1) (a2), J. P. Mackenbach (a2), J. van Os (a3) (a4) and H. W. Hoek (a1) (a5) (a6)



Cannabis use may be a risk factor for schizophrenia. Part of this association may be explained by genotype–environment interaction, and part of it by genotype–environment correlation. The latter issue has not been explored. We investigated whether cannabis use is associated with schizophrenia, and whether gene–environment correlation contributes to this association, by examining the prevalence of cannabis use in groups with different levels of genetic predisposition for schizophrenia.


Case-control study of first-episode schizophrenia. Cases included all non-Western immigrants who made first contact with a physician for schizophrenia in The Hague, The Netherlands, between October 2000 and July 2005 (n=100; highest genetic predisposition). Two matched control groups were recruited, one among siblings of the cases (n=63; intermediate genetic predisposition) and one among immigrants who made contact with non-psychiatric secondary health-care services (n=100; lowest genetic predisposition). Conditional logistic regression analyses were used to predict schizophrenia as a function of cannabis use, and cannabis use as a function of genetic predisposition for schizophrenia.


Cases had used cannabis significantly more often than their siblings and general hospital controls (59, 21 and 21% respectively). Cannabis use predicted schizophrenia [adjusted odds ratio (OR) cases compared to general hospital controls 7.8, 95% confidence interval (CI) 2.7–22.6; adjusted OR cases compared to siblings 15.9 (95% CI 1.5–167.1)], but genetic predisposition for schizophrenia did not predict cannabis use [adjusted OR intermediate predisposition compared to lowest predisposition 1.2 (95% CI 0.4–3.8)].


Cannabis use was associated with schizophrenia but there was no evidence for genotype–environment correlation.


Corresponding author

*Address for correspondence: W. Veling, M.D., Ph.D., Parnassia Psychiatric Institute, Department of Research, Mangostraat 15, 2552 KS The Hague, The Netherlands. (Email:


Hide All
Andreasen, NC, Flaum, M, Arndt, S (1992). The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of General Psychiatry 49, 615623.
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.
Caspi, A, Moffitt, TE, Cannon, M, McClay, J, Murray, R, Harrington, H, Taylor, A, Arseneault, L, Williams, B, Braithwaite, A, Poulton, R, Craig, IW (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×environment interaction. Biological Psychiatry 57, 11171127.
Collip, D, Myin-Germeys, I, Van Os, J (2008). Does the concept of ‘sensitization’ provide a plausible mechanism for the putative link between the environment and schizophrenia? Schizophrenia Bulletin 34, 220225.
Eaves, L, Chen, S, Neale, M, Maes, HH, Silberg, J (2005). Questions, models, and methods in psychiatric genetetics. In Psychiatric Genetics (ed. Kendler, K. S. and Eaves, L.), pp. 1994. American Psychiatric Publishing: Washington, DC.
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, 612618.
Henquet, C, Krabbendam, L, Spauwen, J, Kaplan, C, Lieb, R, Wittchen, HU, van Os, J (2005 a). Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. British Medical Journal 330, 1114.
Henquet, C, Murray, R, Linszen, D, Van Os, J (2005 b). The environment and schizophrenia: the role of cannabis use. Schizophrenia Bulletin 31, 608612.
Henquet, C, Rosa, A, Krabbendam, L, Papiol, S, Fananas, L, Drukker, M, Ramaekers, JG, van Os, J (2006). An experimental study of catechol-O-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31, 27482757.
MacLeod, J (2007). Cannabis use and symptom experience amongst people with mental illness: a commentary on Degenhardt et al. Psychological Medicine 37, 913916.
Moore, THM, Zammit, S, Lingford-Hughes, A, Barnes, TRE, Jones, PB, Burke, M, Lewis, G (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370, 319328.
Murray, RM, Jones, PB, Susser, E, Van Os, J, Cannon, M (eds) (2003). The Epidemiology of Schizophrenia. Cambridge University Press: Cambridge.
Smitten, MH, Smeets, RMW, Van den Brink, W (1998). Composite International Diagnostic Interview (CIDI), Version 2.1. World Health Organization: Amsterdam.
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, 13331341.
Veling, W, Selten, JP, Veen, N, Laan, W, Blom, JD, Hoek, HW (2006). Incidence of schizophrenia among ethnic minorities in the Netherlands: a four-year first-contact study. Schizophrenia Research 86, 189193.
Verdoux, H, Gindre, C, Sorbara, F, Tournier, M, Swendsen, JD (2003). Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study. Psychological Medicine 33, 2332.


Cannabis use and genetic predisposition for schizophrenia: a case-control study

  • W. Veling (a1) (a2), J. P. Mackenbach (a2), J. van Os (a3) (a4) and H. W. Hoek (a1) (a5) (a6)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed