Cannabis controversies: how genetics can inform the study of comorbidity

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.

Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia

“…This increased comorbidity can be explained through several, non-exclusive mechanisms (7) (Figure 1): 1. schizophrenia may cause the development of substance use disorder (8); 2. substance use disorder may lead to the onset of schizophrenia (9); or 3. there may be common underlying risk factors, environmental and genetic, that predispose to both schizophrenia and substance use disorder (10, 11). With the publication of large meta-analyses of genome-wide association studies (GWAS), polygenic risk scores now can be used to measure the shared genetic liability between schizophrenia and substance use disorder, which can lead to better understanding of potential mechanisms for these comorbid conditions.…”

Cannabis and Depression: A Twin Model Approach to Co-morbidity

“…Twin models of co-morbidity would also be a useful tool to study the relationship between cannabis involvement and depression (Agrawal and Lynskey 2014), as both MDD (e.g. Sullivan et al 2000; Kendler et al 2006a) and cannabis dependence (Lynskey et al 2002; Verweij et al 2010) are influenced by genetic factors.…”

Review of Marijuana Use in the Adolescent Population and Implications of its Legalization in the United States

“…Conversely, the negative symptoms of psychosis are conventionally the most difficult to treat, and those psychotic patients with cannabis histories tend to have less severe negative symptoms [25]. The popular theory at present tends to be that cannabis-use may preemptively induce psychosis in genetically susceptible individuals, and it is at present unlikely and incorrect to make a blanket statement that cannabis causes psychosis [31]. However, more research needs to be done to elucidate these connections.…”