Peripheral FAAH inhibitors

Project Leader: Tiziano Bandiera, PhD

The natural cannabis-like substance, anandamide, is produced in injured tissues and activates specialized receptors on pain-sensing terminals, called cannabinoid receptors, which prevent the access of pain-carrying signals to the brain. The compound ARN354 stops the degradation of anandamide, caused by the enzyme fatty acid amide hydrolase (FAAH), and by doing so produces profound analgesic effects in animal models of pain. Importantly, ARN354 does not enter the brain and spinal cord, yet its analgesic actions are equal or superior to those of centrally active analgesics. Because of its remarkable efficacy and favorable safety profile, ARN354 has been advanced to preclinical development for post-operative and nociceptive pain. In parallel with the development of ARN354, D3 is optimizing brain-penetrating FAAH inhibitors for the treatment of central nervous system diseases, such as nicotine addiction and post-traumatic stress disorder, in which preclinical evidence and human polymorphism data suggest a role for anandamide. This project is partially supported by a 5-year grant from the US National Institutes of Health.