Chunk #9 — Endocannabinoid Variants and Childhood Adversity Predict Cannabis Dependence Symptoms and Amygdala Habituation — The Endocannabinoid System and Cannabis Involvement
Given that eCB receptors bind the psychoactive component, THC, in cannabis as well as endogenous ligands similar in structure to THC, it is a promising candidate system for probing genetic vulnerability to cannabis dependence. Chronic cannabis users, for example, show global decreases in CB1 receptor availability (Ceccarini et al., 2013). Correspondingly, animal models have persuasively documented that the psychoactive effects of cannabis are exerted via their interface with these eCB receptors in the central nervous system, particularly CB1 (Lichtman & Martin, 1997; Wiley et al., 2014). For instance, impairment of short term spatial memory is a frequently observed outcome of acute THC administration (Wise et al., 2012), and CB1 receptor antagonism in the hippocampus attenuates this memory disruption, while elevation of AEA and 2-AG levels via simultaneous FAAH and MAGL blockade recapitulates this phenotype (Wise, Thorpe, & Lichtman, 2009). Despite this strong preclinical evidence, much of the extant literature on specific genes and polymorphisms within the eCB system influencing cannabis phenotypes (e.g., Filbey, Schacht, Myers, Chavez, & Hutchison, 2010; Haughey, Marshall, Schacht, Louis, & Hutchison, 2008; Schacht, Selling, & Hutchison,
