Cannabinoid Modulation of Fear Extinction Brain Circuits: A Novel Target to Advance Anxiety Treatment
Christine A. Rabinak and K. Luan Phan
Affiliation: Department of Psychiatry, University of Michigan, Rachel Upjohn Building, 4250 Plymouth Road, Ann Arbor, MI 48109-2700.
Keywords: Cannabinoid, fear extinction, cognitive enhancer, ventromedial prefrontal cortex, hippocampus, amygdala, anxiety.
Anxiety disorders, such as post-traumatic stress (PTSD), panic, and phobic disorders, can be conceptualized as a failure to inhibit
inappropriate fear responses. A common, effective treatment strategy involves repeated presentations to the feared cue without any
danger (extinction). However, extinction learning has a number of important limitations, and enhancing its effects, generalizability and
durability via cognitive enhancers may improve its therapeutic impact. In this review we focus specifically on the role of the cannabinoid
system in fear extinction learning and its retention. We address the following questions: What are the neural circuits mediating fear extinction?;
Can we make fear extinction more effective?; Can cannabinoids facilitate fear extinction in humans?; How might the cannabinoid
system effect fear extinction? Collectively, translational evidence suggest that enhancing cannabinoid transmission may facilitate
extinction learning and its recall, and that the cannabinoid system is a potential pharmacological target for improving the active learning
that occurs during exposure-based behavioral treatments prompting future research in terms of mechanisms research, novel treatment approaches
(‘cognitive enhancers’), and pharmacotherapeutic drug discovery.
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