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Review
. 2014 Mar;109(3):360-70.
doi: 10.1111/add.12436. Epub 2014 Jan 19.

Cannabis controversies: how genetics can inform the study of comorbidity

Arpana Agrawal  1 , Michael T Lynskey
Affiliations
Review

Cannabis controversies: how genetics can inform the study of comorbidity

Arpana Agrawal et al. Addiction. 2014 Mar.

Abstract

Aims: To review three key and controversial comorbidities of cannabis use-other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective.

Design: Selective review.

Results: Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis.

Conclusions: Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play.

Keywords: Cannabis; comorbidity; gateway; genetics; psychosis; twin.

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Figures

FIGURE 1
FIGURE 1
Multiple possible mechanisms that may link cannabis use and misuse to mental health outcomes, including other illicit drug use, depression and suicide as well as psychosis. Panel A: Cannabis use directly causes outcome; A1 depicts how this causal effect may be exerted via alterations in biological pathways (such as receptor cross-tolerance) while A2 demonstrates a similar causal effect mediated by environmental exposures (such as access to drug supplier). Panel B demonstrates reverse causation, such as self-medication. Panel C shows how cannabis use and outcomes might be related via common genetic and environmental underpinnings. Panel D illustrates stress-diathesis (or gene-environment interaction) – cannabis use modifies the extent to which diathesis (such as select genotypes in the catechol-o-methyltransferase gene) influences the outcomes.
FIGURE 2
FIGURE 2
The discordant twin design is illustrated. Pairs of twins (MZ=monozygotic/identical; DZ=dizygotic/fraternal) discordant for cannabis use are matched to varying degrees for genetic and environmental factors allowing for residual associations to be explained by unshared factors. Pairs of unrelated individuals are shown for comparison.
FIGURE 3
FIGURE 3
Hypothetical results expected from a discordant twin study, for discordant pairs of MZ, DZ and unrelated individuals, which can be used to infer the nature of the association between cannabis use and outcomes. If the association is entirely due to causal or individual-specific factors then the magnitude of association is invariant to degree of relatedness. In contrast, if genes or family environment play a role, then matching discordant pairs of individuals for these factors results in an attenuation of the association.
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References

    1. European Monitoring Centre for Drugs and Drug Addiction. European Drug Report 2013: Trends and developments. Lisbon: EMCDDA; 2013. - PubMed
    1. Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE. Monitoring the Future national results on adolescent drug use: Overview of key findings, 2012. Ann Arbor: Institute for Social Research: The University of Michigan; 2013.
    1. Australian Institute of Health and Welfare. 2010 National Drug Strategy Household Survey Report. Cat no. PHE. Vol. 145. Canberra: AIHW; 2011. Report No.: Data statistics series no. 25.
    1. Degenhardt L, Chiu WT, Sampson N, Kessler RC, Anthony JC, Angermeyer M, et al. Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys. PLoS Med. 2008 Jul 1;5(7):e141. - PMC - PubMed
    1. Nutt D, King LA, Saulsbury W, Blakemore C. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet. 2007 Mar 24;369(9566):1047–1053. - PubMed

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