A natural compound for chilling out?

As I sit here typing this morning, I'm munching on cocoa nibs, inspired by Friedman's review pointing to the work of Dincheva et al. on a gene whose enzyme product (fatty acid amide hydrolase, FAAH) deactivates and thus regulates the action of our endogenous cannabinoid anandamide (which cocoa nibs contain in small amounts).

Individuals with a common human mutation in the FAAH gene have higher brain levels of anandamide and lower levels of background anxiety, due to enhanced connectivity between the frontal lobes and the amygdala. Here is the Dincheva abstract describing actions of the FAAH gene in a mouse model:

Cross-species studies enable rapid translational discovery and produce the broadest impact when both mechanism and phenotype are consistent across organisms. We developed a knock-in mouse that biologically recapitulates a common human mutation in the gene for ​fatty acid amide hydrolase (​FAAH) (C385A; rs324420), the primary catabolic enzyme for the endocannabinoid ​anandamide. This common polymorphism impacts the expression and activity of ​FAAH, thereby increasing ​anandamide levels. Here, we show that the genetic knock-in mouse and human variant allele carriers exhibit parallel alterations in biochemisty, neurocircuitry and behaviour. Specifically, there is reduced ​FAAH expression associated with the variant allele that selectively enhances fronto-amygdala connectivity and fear extinction learning, and decreases anxiety-like behaviours. These results suggest a gain of function in fear regulation and may indicate for whom and for what anxiety symptoms ​FAAH inhibitors or exposure-based therapies will be most efficacious, bridging an important translational gap between the mouse and human.