Researchers at the University of Cincinnati College of Medicine presented results of one of the largest smoking cessation trials ever conducted in the United States, STRATUS-US (STudies with Rimonabant And Tobacco USe). The findings show that a new drug, rimonabant, doubled the odds of quitting smoking compared with placebo, markedly reduced post-cessation weight gain at 10 weeks, and was well-tolerated.

“Smoking cessation is an enormous struggle for many people,” said Robert Anthenelli, M.D., one of the principal investigators in the STRATUS US trial and an associate professor of Psychiatry at the University of Cincinnati College of Medicine and Cincinnati VA Medical Center. “People who smoke are at high risk for cardiovascular disease. It is imperative to do anything and everything we can to treat tobacco dependence. Rimonabant represents a potentially promising new treatment option that can help people stop smoking while curbing post cessation weight gain. This may be a major step forward in smoking cessation.”

Rimonabant is the first in a new class of drugs called Selective CB1 Blockers. The drug works by inhibiting the CB1 receptor, one of two receptors found in the EndoCannabinoid System (or EC System), that are located in the brain and in other parts of the body. Associated with systems regulating the body’s intake of food, the EC system is also involved in tobacco dependency. Chronic tobacco use over-stimulates the EC system creating an imbalance.

By blocking the CB1 receptor, rimonabant helps restore balance to the EC system resulting in reduced dependence on tobacco. In addition, in other clinical trials with rimonabant, researchers discovered that CB1 receptors are also found in adipose tissue (fat cells), which are associated with lipid and glucose metabolism.

Blocking CB1 receptors in this part of the body has shown, in a recently completed obesity clinical trial called RIO-LIPIDS, results of which were also presented at the American College of Cardiology, that rimonabant not only significantly induces significant weight loss but reduces abdominal fat in overweight/obese people with untreated dyslipidemia, and also increases HDL-cholesterol (good cholesterol), lowers triglycerides, and significantly improves impaired glucose and insulin levels, all contributing risk factors for cardiovascular disease.

“It is widely known that smoking is linked to respiratory diseases and lung cancer, but smokers are also at 70% greater risk for cardiovascular disease than non smokers,” said Dr. Anthenelli.

“Since these two studies show that rimonabant treats obesity and related metabolic disorders in overweight/obese patients, and also helps people to quit smoking without significant post-cessation weight gain, we may have a very promising new approach for managing two major and preventable risk factors for cardiovascular disease with one and the same drug.”

Johnson and Johnson announced it is discontinuing its current clinical development program for a time-release formulation of Topamax (topiramate) for use in treating in obesity — the latest weight-loss hope to fade as a result of troublesome side-effects.

Topamax is widely used to treat epilepsy and seizures, and clinical trials had suggested that it might also be highly effective in promoting weight loss.

But a clinical study of Topamax for weight loss was halted because of side-effects related to the central nervous system.

The most common side effect for those taking Topamax was paresthesia, a tingling, “pins and needles” sensation in the extremities, which occurred in 73 percent of patients taking the higher dose and 46 percent of patients taking the lower dose of the drug.

Topamax use was also linked to problems with memory. Some 18 percent of dieters in the trial taking higher doses of the drug reported memory problems, compared with 14 percent of those taking the lower dose and 6 percent of those taking a placebo.

Johnson and Johnson subsequently said it was attempting to develope a time-release version of the Topamax that it hoped would minimize side effects and be more appropriate for dieters.

“Data from a recently completed phase II clinical study with the controlled release formulation of topiramate showed that the controlled release formulation did not provide significant advantages in this population compared to previously conducted studies using the immediate release formulation,” Johnson and Johnson said in announcing it was halting development.

The company emphasized that the move was not based on any new safety information and did not impact the use of Topamax as an antiepileptic drug. It currently is approved to treat various types of epileptic seizures in more than 95 countries, and for the prevention of migraine headaches in more than 28 countries.