Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents

Pathological anxiety is the most common type of psychiatric disorder. The current first-line anti-anxiety treatment, selective serotonin/noradrenaline reuptake inhibitors, produces a delayed onset of action with modest therapeutic and substantial adverse effects, and long-term use of the fast-acting anti-anxiety benzodiazepines causes severe adverse effects. Inhibition of the fatty acid amide hydrolase (FAAH), the endocannabinoid N -arachidonoylethanolamine (AEA) degradative enzyme, produces anti-anxiety effects without substantial "unwanted effects" of cannabinoids, but its anti-anxiety mechanism is unclear.