Consistent with evidence of a potential shared mechanism of risk, marijuana dependence frequently co-occurs with CD (Miller et al 1990). Further, cocaine administration increases levels of anandamide in striatum. This effect decreases by pharmacological inhibition of DA-2-like receptors (Centonze et al 2004). Besides the reduction effect on anandamide release by pharmacological inhibition of D2-like receptors, administration of D2-like receptor agonists increased anandamide release (Giuffrida et al., 1999). Additionally, blockade of CB1 receptors can partially prevent the inhibitory effect of cocaine on GABA transmission (Centonze et al 2004). Blockade of CB1 can also decrease the DA signal induced by cocaine in NAc (Cheer et al 2007). Endocannabinoid system-mediated synaptic plasticity, e.g., long-term potentiation (eCB-LTP) and long-term depression (eCB-LTD), have been identified in brain (Carlson et al 2002; Chevaleyre et al 2006), and the endocannabinoid system is involved in the mediation of cocaine-induced LTD in midbrain DA neurons (Pan et al 2008). Animal studies further have shown that, after a prolonged withdrawal period, pretreatment with a CB1 antagonist (SR141716) attenuates cocaine relapse induced by exposure to cocaine or cocaine-related cues, while pretreatment
