ABSTRACT:
Cannabis sativa is a plant containing over 70 active compounds called cannabinoids (Schoedel and Harrison, 2012). The psychoactive effects of cannabinoids are abused worldwide by about 20% of young people, who report regular or heavy use of the cannabis plant (Moore et al., 2007). Delta-9-tetrahydrocannabinol (THC), the most prevalent cannabinoid in the plant, has been found to be responsible for producing most of the desirable effects of marijuana (Gaoni and Mechoulam, 1964). In line with that, the use of modern hydroponic cannabis farms has resulted in growing strains containing higher levels of THC, while keeping other cannabinoids at negligible levels (Hardwick and King, 2008). Accordingly, it may be assumed that the presence of THC-dominated cannabis plants on the market leads to the risk of more severe consequences of abuse, since THC has been associated with induction of psychotic symptoms both in an acute intoxicated state (D’Souza et al., 2004), as well as in the long-term (Kuepper et al., 2010). Consequently, in the current paper we propose that cannabidiol (CBD), another abundant compound of cannabis, might have an impact on cognition and emotional processing, which is opposite to the effect of THC. Moreover, we suggest that the effects of CBD would be worth investigating in regard to the modulatory role of the anterior cingulate cortex (ACC)—a brain region where both affective and cognitive information converge (Bush et al., 2000; Botvinick et al., 2001; Paus, 2001).
The pharmacology of CBD is well studied [for a review see Mechoulam et al. (2002)]. Its effects are distinct and frequently opposite to those of THC (Fusar-Poli et al., 2009). Whereas THC is a cannabinoid receptor type 1 and 2 (CB1r and CB2r) agonist, CBD has low affinity and a partially antagonistic effect at these receptors (Pertwee, 2008). Furthermore, CBD has been shown to be a serotonin receptor (5-HTr) agonist (Campos and Guimarães, 2008; Zanelati et al., 2010; Gomes et al., 2011). In recent years CBD has received renewed attention from researchers, mainly due to its anxiolytic (e.g., Zuardi et al., 1982, 1993; Crippa et al., 2004, 2011; Fusar-Poli et al., 2009; Bergamaschi et al., 2011) and antipsychotic effects (e.g., Zuardi et al., 2009; Bhattacharyya et al., 2010; Schubart et al., 2011). The therapeutic value of CBD in clinical contexts is currently being explored (Zuardi et al., 2006, 2009; Hallak et al., 2009). Moreover, in a recent review Schier et al. (2012) suggested that CBD neither produces psychoactive effects, nor has an impact on cognition. In the light of up-to-date research, this claim may be considered unwarranted, since CBD has been shown to differ with THC in terms of activation of brain regions during tasks involving response inhibition (Borgwardt et al., 2008), emotional processing (Fusar-Poli et al., 2009) and verbal memory (Bhattacharyya et al., 2010). Additionally, as far as only the anxiolytic effect of CBD is considered, it may be assumed that it influences cognition through, for instance, reducing attention bias toward threatening stimuli (Bar-Haim et al., 2007). In spite of that, the effect of CBD on cognitive performance has been largely unexplored.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629308/