CB1 receptors as a pharmacological target for treating anxiety disorders (Gaetani et al., 2003; Gaetani et al., 2009; Hill and Gorzalka, 2009; Witkin et al., 2005). However, some important issues need to be addressed if CB1 agonists are to be used as a treatment for anxiety disorders. For instance, the subjective effects of THC tend to be biphasic; low doses generally promote anxiolytic-like effects, whereas higher doses may induce anxiogenic-like effects (D’Souza et al., 2004; Genn et al., 2004; Viveros et al., 2005). Moreover, we found THC administration facilitates extinction of conditioned fear in participants with minimal or no previous history of marijuana usage; however we cannot generalize these findings to chronic marijuana users. In fact, chronic heavy marijuana smokers experience a disruption or alteration in frontal-limbic network, in the absence of intoxication, which in turn could affect the efficacy of THC on extinction learning (Cornelius et al., 2010; Gruber et al., 2009). Also, because some 13 of the 29 participants had minimal prior exposure to marijuana (mean: 1.2 times over lifetime), these findings also require replication in a THC-naïve cohort. Future studies are needed to address these important issues.
