In a new report, researchers have found that metformin, an inexpensive drug commonly used to treat patients with type 2 diabetes, appears to block symptoms of nicotine withdrawal in rodents. 

Dr Sangwon Kim, of the Johns Hopkins University School of Medicine’s Division of Endocrinology, Diabetes and Metabolism, along with researchers at the University of Pennsylvania, found that laboratory mice that had been exposed to a two-week regimen of nicotine displayed no withdrawal symptoms when given the diabetes drug metformin.

Based on previous studies that identified how nicotine affects brain chemistry, Dr Kim and his colleagues hypothesized that metformin might eliminate anxiety, irritability and other withdrawal symptoms.

For the new study, the research team focused on activating an enzyme known as an AMP-activated protein kinase, or AMPK, which — among other roles — stimulates the breakdown of glucose for energy. Dr Kim and his colleagues discovered that the AMPK pathway is activated in mammals following chronic nicotine use, but is repressed during nicotine withdrawal. They set out to find whether AMPK, stimulated by metformin, could lessen or even eliminate the symptoms of nicotine withdrawal.

"This is the first-ever study to examine AMPK’s relation to nicotine dependence," says Dr Kim.

Among the effects of metformin, which suppresses liver glucose production, is the activation of AMPK. In proper doses, the researchers thought, metformin might treat the withdrawal symptoms without the side effect of throwing blood glucose out of balance.

Dr Kim and colleagues found that nicotine-treated mice that were given metformin displayed none of the anxiety or other negative effects of withdrawal. Metformin, the researchers found, completely prevented anxious behaviours caused by nicotine withdrawal at doses that had no effect on body weight, food consumption or glucose levels. Dr Kim says the research suggests that metformin, because of its long-term record of safety and relative lack of side effects, has "real potential" as a smoking cessation aid if clinical trials confirm the findings in mice.

Additional authors are Sunghee Jin of the Johns Hopkins University School of Medicine and Julia K. Brynildsen, Bridgin G. Lee, Isaac J. Perron and Julie A. Blendy of the University of Pennsylvania Perelman School of Medicine. The authors declare no conflicts of interest.

The study was funded by the National Institute of General Medical Sciences, the National Institute on Drug Abuse, the National Institute of Diabetes and Digestive and Kidney Diseases and a National Center for Advancing Translational Sciences award.

this week in The Proceedings of the National Academy of Sciences of the United States of America (PNAS).

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