Dementia Drugs May Help Smokers Quit

Megan Brooks

February 18, 2016

Cognition-enhancing medications used to treat patients with Alzheimer's disease may have a role in smoking cessation, new research suggests.

In a small study, smokers treated with the acetylcholinesterase inhibitor (AChEI) galantamine (Razadyne, Janssen Pharmaceuticals, Inc) smoked fewer cigarettes and found cigarettes less satisfying, even before they tried to quit.

"Many smokers report having difficulty concentrating when they quit smoking, and there is evidence that this increases smoking relapse rates. This suggested to us that targeting cognitive function during a quit attempt might be a useful treatment strategy," Rebecca Ashare, PhD, and Heath Schmidt, PhD, of the University of Pennsylvania Perelman School of Medicine, in Philadelphia, who led the research, told Medscape Medical News.

In previous work, the researchers demonstrated that acute administration of an AChEI attenuates nicotine seeking and consumption in rodents, suggesting that these drugs could be repurposed for smoking cessation.

In their latest study, they showed that repeated administration of an AChEI reduces nicotine reinforcement in rats and smoking behavior in human smokers at doses not associated with tolerance or adverse effects.

The findings were published online January 19 in Translational Psychiatry.

"Compelling Evidence"

The clinical trial included 33 adult smokers (average age, 43 years) who reported smoking an average of 14.8 cigarettes per day for 25 years. They received either 2 weeks of daily treatment with galantamine (8.0 mg during week 1 and 16.0 mg during week 2) or placebo. The participants smoked for the majority of the trial, but during a weeklong "monitored abstinence" period, they were encouraged to do their best not to smoke.

The researchers found that those taking galantamine reduced the number of cigarettes smoked by 2.3 cigarettes per day (12%); by comparison, the placebo group reduced the number by 1.3 cigarettes per day (7%). Galantamine also significantly reduced smoking satisfaction and reward compared with placebo.

"This is all really promising," Dr Ashare said in a news release. "If people are smoking less, and they don't enjoy their cigarettes as much, we hope this will lead to better quit rates."

The next step, said the investigators, is to evaluate whether these medications prevent relapse. They are collecting those data.

The findings, they added, suggest that AChEIs, which are already approved by the US Food and Drug Administration (FDA) for attenuating cognitive decline in patients with Alzheimer's disease, could offer a novel treatment for smoking cessation.

"Despite the fact that we have treatments for smoking cessation, the problem is that they are only effective for a small portion of smokers. However, it's very costly and time consuming to develop new pharmacotherapies. Repurposing FDA-approved medications bypasses many of these hurdles, as these drugs have already been proven safe. That is why, for our translational study, we selected the cholinesterase inhibitors," the investigators explained.

"The consistency between our preclinical and clinical findings provides compelling evidence that a larger clinical trial testing the efficacy of AChEIs for smoking cessation is warranted," they write.

Blunting Effect

Mehmet Sofuoglu, MD, PhD, professor of psychiatry, Yale University School of Medicine, in New Haven, Connecticut, said he "fully agrees that medications enhancing cognitive function may have a role for the treatment of smoking cessation. In fact, difficulty concentrating is one of the most common complaints among smokers trying to abstain from smoking. Medications that increase acetylcholine levels in the brain may be particularly effective to improve cognitive functions associated with smoking abstinence," Dr Sofuoglu, who was not involved in the study, told Medscape Medical News.

These new findings, Dr Sofuoglu noted, "are consistent with our earlier findings, where we found that in abstinent smokers, galantamine treatment, compared to placebo, enhanced certain cognitive functions, including sustained attention and response inhibition. Galantamine treatment also reduced craving for cigarettes and blunted the pleasurable effects of nicotine.

"Based on these promising findings, we received an NIH [National Institutes of Health] grant to test the efficacy of galantamine, compared to placebo, for smoking cessation. We are currently analyzing the data, and the results should be available with the next 2 to 3 months," Dr Sofuoglu said.

The study was supported by grants from the Center for Interdisciplinary Research on Nicotine Addiction and the Abramson Cancer Center, both at the University of Pennsylvania, and by a grant from the American Cancer Society. The authors and Dr Sofuoglu report no relevant financial relationships.

Transl Psychiatry. Published online January 19, 2016. Abstract

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