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  • br Conclusion br Introduction Adolescence is a


    Introduction Adolescence is a significant period of psychosocial development, with increases in novelty-seeking and risk-taking behaviors (Adriani et al., 1998; Romer et al., 2010; Trimpop et al., 1998). Experimentation with drugs of abuse – especially alcohol, tobacco, and cannabis, is typically initiated during this phase (Chen and Kandel, 1995). As cannabis becomes more available and public opinion trends towards acceptance, adolescents may have increased access to the substance. Current rates of cannabis use among adolescents are high, with a quarter of all 10th graders, and over a third of all 12th graders in the US reporting trying cannabis at least once (SAMHSA, 2014). Chronic use also appears to be growing; in 2008, 5.5% of users aged 12 and up reported near daily use while in 2013 this rate had risen to 8.1% (SAMHSA, 2014). These increasing rates of use are consequential in that about 10% of those who try cannabis will become weekly users in adulthood (Hall and Pacula, 2003). Furthermore, adolescent beliefs about the risks associated with cannabis appear to be declining (Johnston et al., 2011). Adolescence is also a period of marked neural development including gross volume changes, myelination, synaptic pruning, and receptor proliferation (Spear, 2000). These changes are especially large in the prefrontal cortex (PFC) (Gogtay et al., 2004; Whitford et al., 2007), amygdala, hippocampus, and striatum, and are governed in part by the endogenous cannabinoid system (Bossong and Niesink, 2010). Interestingly, the primary cannabinoid receptor, CB1, is found in high concentrations in these cognitive and affective regions of the prostaglandin endoperoxide synthase (Glass et al., 1997; Herkenham et al., 1991; Katona et al., 2001), and appears to be fully expressed by adolescence (Belue et al., 1995; de Fonseca et al., 1993; Morozov and Freund, 2003; Romero et al., 1997). Studies have shown that exogenous cannabinoids can interfere with the endogenous system (Hoffman et al., 2007; Mato et al., 2004). Given the natural maturation occurring in the brain during adolescence, and the propensity towards cannabis use, the consumption of exogenous cannabinoids during adolescence may disrupt typical neurodevelopment within the cognitive and affective neural systems. Mounting evidence supports the relationship between early cannabis use and mood disorders (Wittchen et al., 2007), even with relatively low levels of use (Cheung et al., 2010). Hence, Cordycepin is crucial to investigate the consequences of cannabis use on emotional development. Although numerous studies have associated cannabis use in adolescence with an increased likelihood of schizophrenia and/or other affective disorders (Arseneault et al., 2004; Degenhardt and Hall, 2006; Fergusson et al., 2006; Hall, 2006; Linszen and van Amelsvoort, 2007; Manrique-Garcia et al., 2012) there is relatively little research on the impact of cannabis use from a cognitive and affective neuroscience perspective. The amygdala has a high density of CB1 receptors, notably in the basal and lateral nuclei (Katona et al., 2001). In adulthood, increased amygdala activity is associated with major depressive disorder (Drevets, 2001; Sheline et al., 2001), and generalized social phobia (Evans et al., 2008; Phan et al., 2006). In adolescence, the amygdala was found to yield stronger responses to fearful faces than adults (Thomas et al., 2001), and greater amygdala reactivity may account for adolescent vulnerability to mood disorders (Guyer et al., 2008a; Monk et al., 2008; Roberson-Nay et al., 2006). In consideration of the amygdala\'s role in the endocannabinoid system and affective processing, adolescent vulnerability to prostaglandin endoperoxide synthase mood disorders and propensity for cannabis use, it is important to assess functional differences in this region in cannabis-using teenagers. Using an animal model, Rubino and colleagues (2008), and Schramm-Sapyta and colleagues (2007) examined the relationship between anxiety and THC exposure in adolescent and adult rats. Findings indicate that adolescent rats exhibit elevated signs of anxiety, depression, and anhedonia when treated with THC compared to placebo. Translating these findings to humans may imply cannabis use in adolescence is related to differences in the generation and regulation of affect.