Side Effects Derail Cannabinoid Receptor Blockers for Obesity

Reprinted from Eating Disorders Review
January/February 2009 Volume 20, Number 1
©2009 Gürze Books

The endocannabinoid system’s effect on appetite, food intake, and energy balance has been of great interest for antiobesity treatment, and as a result several products have been developed and used in Europe. However, despite their early promise for treating obesity, several cannabinoid receptor 1 (CB1R) blockers for obesity have been cancelled due to side effects. CB1R blockers were approved for antiobesity treatment in Europe about 2 years ago, but were never approved in the U.S. Sanofi-Aventis, Merck, and Pfizer, and others have now halted their CB1R programs. Agents such as rimonabant, and taranabant and CP-945,598, which were in clinical trials, are on hold.

The drugs inhibited the mechanisms for coping with stress and anxiety, making depression and other psychiatric side effects more likely. Researchers have not given up on the concept, and are looking at developing variations of these drugs that act only in the peripheral nervous system, rather than centrally, like the cancelled compounds. These agents would not cross the blood-brain barrier and thus would be less likely to affect mood (Nature Reviews, Dec. 2008; 7:961). Other variations of the CB1R blockers, combined with lifestyle changes, may produce fewer side effects in patients with specific patterns of obesity (e.g., an abdominally obese person with no history of depression.

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