Many of the neural and behavioral effects of exogenously administered cannabinoids can be traced directly to activation of the `endocannabinoid' (ECB) system [10] – a set of neurochemicals and cognate receptors densely expressed throughout the brain [11]. The discovery of the ECB system raised the possibility that ECBs could be important modulators of anxiety, and might contribute to individual differences in anxious temperament and risk for anxiety disorders. It also led to the notion that targeting components of the ECB system could represent a novel therapeutic approach to developing effective anxiolytic medications devoid of the unwanted effects of cannabis (e.g., cognitive impairment, abuse liability) [4,12] (Box 1). That is, selective alleviation of symptoms could be produced by increasing levels of endogenously activated ECBs and avoiding widespread behavioral effects caused by exogenously applied, ubiquitously activating cannabinoid receptor type 1 (CB1R) agonists.
