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Can cannabinoid type 1 receptor antagonists help smokers to quit, and could they also reduce the amount of weight gained during the quitting process?

Cahill K, Ussher MH
Published Online: 
11 July 2012

Long-term use of nicotine can upset the endocannabinoid system in the brain, which controls food intake and energy balance. Rimonabant and similar drugs may help smokers to quit by rebalancing the system, which then reduces nicotine and food cravings. We searched our own specialised register of controlled trials. We also contacted Sanofi Aventis, the manufacturers of rimonabant, and researchers who presented early findings at conferences. We found two randomized controlled trials (RCTs) of rimonabant for smoking cessation, covering 1567 smokers, and one RCT of rimonabant for relapse prevention covering 1661 quitters. The available information shows that rimonabant at the 20 mg dose increased by 1½-fold the chances of not smoking at one year, compared with placebo. Rimonabant 5 mg did no better than placebo at any time point. In the relapse prevention trial, smokers who quit successfully with rimonabant 20 mg were 1½ times more likely to remain abstinent on active treatment (5 mg or 20 mg for 42 weeks) than on placebo. For those who quit successfully on 5 mg, neither active nor placebo treatment appeared to benefit them in avoiding relapse. This inconsistent picture makes it difficult to find a clear benefit for rimonabant in preventing relapse. One trial of taranabant (317 smokers) did not find a benefit for treatment over placebo, and the taranabant group suffered more side effects than the placebo group. Main side effects for rimonabant included nausea and upper respiratory tract infections, and serious harms were reported to be low. For taranabant, the main side effects included problems with digestive, nervous, psychiatric, skin and blood vessel organ systems. For both drugs, the number and severity of the side effects increased in those taking higher doses. Although the evidence on weight change is sparse in these trials, weight gain was reported to be significantly lower among the rimonabant 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight on 20 mg, while normal weight smokers did not. Taranabant also limited weight gain during cessation attempts. In 2008 both rimonabant and taranabant were withdrawn by the manufacturers, because of links to mental disorders and unacceptable side effects.