The effects of exogenous cannabis and endocannabinoids are mediated by cannabinoid receptor 1 (CNR1; a.k.a. CB1 or CB1R), which is widely expressed in the brain, including prefrontal cortex and medial temporal lobe (Pazos, Nunez, Benito, Tolon, & Romero, 2005). CNR1 is localized to Chr 6q14-q15, a schizophrenia susceptibility locus (Kohn & Lerer, 2005). Previous schizophrenia-CNR1 genetic association studies, restricted mostly to two CNR1 variants (i.e. rs1049353 SNP and an (AAT)n trinucleotide repeat), have found mixed results (Chavarría-Siles et al., 2008; Seifert, Ossege, Emrich, Schneider, & Stuhrmann, 2007). No studies have comprehensively investigated the effects of CNR1 on brain morphometric and neurocognitive phenotypic features of schizophrenia. The goal of this study is to examine the interactions between CNR1 genetic variants and heavy marijuana misuse on brain volumes and cognitive function among schizophrenia patients. Our hypothesis is that patients with specific CNR1 genotypes are more vulnerable to the effects of heavy marijuana misuse, and will show greater brain volume deficits and cognitive impairment than patients without marijuana misuse.
