More MS news articles for July 2001

Anandamide Regulator May Offer Pain Relief Without Side Effects of Marijuana

WESTPORT, CT (Reuters Health) Jul 23 - Fatty acid amide hydrolase (FAAH) appears to be the primary regulator of anandamide, an endogenous cannabinoid receptor ligand. Researchers suggest that inhibitors of FAAH could be as effective as marijuana in the treatment of pain and neuropsychiatric disorders without the associated adverse effects.

Anandamide is a brain lipid whose cannabinoid properties in vivo are weak, which researchers attribute to its rapid catabolism. Dr. Benjamin F. Cravatt, of The Scripps Research Institute, in La Jolla, California, and associates found that FAAH knockout mice are less responsive to pain.

As reported in the online early edition of the Proceedings of the National Academy of Sciences for July 31, the knockout mice exhibited hypomotility, analgesia, catalepsy, and hypothermia when treated with anandamide, effects that lasted 2 to 4 hours. The investigators note that these effects are similar to those observed when rodents are treated with tetrahydrocannabinol, the active ingredient in marijuana. In wild-type mice, anandamide failed to produce any significant effects.

Anandamide's effects in the knockout mice were completely blocked by pretreatment with the cannabinoid receptor antagonist SR141716A. Further supporting the role of FAAH in anandamide metabolism was the high concentration of anandamide found in the brains of knockout mice, approximately 15 times the levels found in the brains of wild-type mice.

"Inhibitors of FAAH might be more selective than the endogenous ligand itself for treating pain," Dr. Cravatt told Reuters Health. "It will be interesting to see, when we inject FAAH inhibitors, if we get the reduction in pain sensitivity without the other side effects of cannabinoids."

Dr. Cravatt is assuming that by blocking FAAH, endocannabinoids stimulated by pain would "hang around longer in those pathways in which pain transmission is occurring." If so, FAAH inhibitors could achieve analgesia without the addiction, cognitive defects, and motility defects associated with marijuana.

Online Proc Natl Acad Sci USA 2001;98:9371-9376.

Copyright © 2001 Reuters Ltd