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Nixing Withdrawal Symptoms

By Macaela Mackenzie
Sangwon Kim is associate director of Endocrinology, Diabetes and Metabolism Research Laboratories at Johns Hopkins.

Ditching smoking is notoriously difficult. Smokers who decide to quit are faced with the daunting prospect of dealing with nicotine withdrawal and all the irritability, anger, and anxiety that can come with it. But according to a new study, reformed smokers may not be destined for a similar fate. A drug that’s already commonly prescribed to patients for diabetes may help block nicotine withdrawal’s nastiest side effects.

Cigarette smoking is the leading cause of preventable diseases in the United States. Nearly seven in 10 smokers report wanting to quit, but withdrawal symptoms make snuffing out a major challenge. Currently, approved treatments used to ease cessation are limited; they involve nicotine replacement products and medication used to reduce cravings for cigarettes. While these treatments help to some extent, they don’t address the root cause of withdrawal.

Kim and his team wanted to comprehend the anxiety-inducing effects of withdrawal, which previous studies have shown often contribute to failed attempts at quitting.

To find a more direct way to treat the problem, Johns Hopkins endocrinologist Sangwon Kim and researchers from the University of Pennsylvania teamed up to conduct a study in mice to better understand what happens in the brain in the absence of nicotine. Specifically, Kim and his team wanted to comprehend the anxiety-inducing effects of withdrawal, which previous studies have shown often contribute to failed attempts at quitting. They began by zeroing in on a specific enzyme known to stimulate cells into breaking down glucose and turning it into energy.

In mice, Kim and his colleagues found that this particular enzyme was activated after chronic nicotine use – but during withdrawal, enzyme levels dropped off.

Enter metformin, a commonly prescribed drug used to treat type 2 diabetes. In addition to regulating glucose production in diabetes patients, it’s known to stimulate enzyme levels and reduce anxiety. Kim and his team theorized that the drug could potentially reduce the anxiety-riddled aftermath of nicotine withdrawal by keeping enzyme levels up. To test it, the mice were given two weeks of nicotine exposure followed by exposure to metformin. They found the drug completely prevented withdrawal-induced anxiety in the mice, without causing any other side effects such as weight gain or a change in glucose levels.

While no drug is expected to be a magic bullet for smokers, Kim is optimistic about metformin’s potential to boost success rates for smoking cessation. Even better, metformin is just one of many known similar drugs already approved for human use. “There are so many candidate drugs that can be tested for this purpose,” Kim says. “I think they could be very useful and effective.”

Daniel Downey

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