Extinction learning itself is thought to involve active suppression of memories via processes different from normal forgetting. In humans, extinction learning has been powerful in the psychological treatment of ► anxiety disorders which involves "exposure therapy.'' Recent research has shown the strength of combining psychological treatments with pharmacotherapies in enhancing extinction learning. Preclinical studies have demonstrated the potential of augmenting extinction learning by boosting central glutamatergic neurotransmitter system functioning. In particular, the previously widely used antituberculosis drug, d-cycloserine (DCS) - which is a partial agonist at central glutamatergic NMDA-receptors -enhances the response to exposure therapy in patients with social phobia, fear of heights, and ► obsessive-compulsive disorder. In addition to these trials of DCS-related facilitation of exposure therapy, animal behavioral research also suggests that DCS may facilitate extinction of cocaine-induced ► conditioned place preference (CPP). This facilitative effect on extinction is also long-lasting and resistant to reinstatement (i.e., relapse). In humans, however, DCS has shown limited efficacy in enhancing fear extinction, but appears to enhance fear memory consolidation.
Cannabidiol (CBD) is a naturally occurring compound extracted from the Cannabis sativa plant. The pharmacology of CBD is not completely understood, but it is thought that it weakly binds to CB1 and CB2 receptors, functionally blocking the reuptake and hydrolysis of ► anandamide, an endogenous cannabinoid. As discussed above, the endocannabinoid system is thought to play a key role in the brain's natural forgetting mechanisms. There is now also an extensive preclinical literature examining the role of CB1 receptors in extinction learning. CB1-receptor knock-out mice exhibit impaired extinction learning and administration of exogenous CB1-receptor antagonists impairs the extinction of fear behaviors. Conversely, CB1 receptor agonists, eCB membrane transport inhibitors and CBD itself have been shown to facilitate fear extinction. CBD, like DCS, has also been found clinically to enhance the extinction of cocaine- and amphetamine-related CPP.
There is a clear parallel between fear extinction in animals and exposure therapy in humans. In the future, therefore, compounds which aid extinction of memories may have an important therapeutic role in treating clinical conditions such as addiction and anxiety.
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