Recent CDC estimates indicate that cigarette smoking remains the leading preventable cause of death in the United States. As a result, researchers have focused on addressing the most significant factor preventing smokers from quitting: nicotine withdrawal symptoms.
In a study conducted at the University of Pennsylvania and Johns Hopkins School of Medicine, researchers discovered that metformin, a first-line drug treatment for type-2 diabetes, may also alleviate nicotine withdrawal symptoms. The findings were published in the PNAS journal.
The research team investigated the connection between AMP-activated protein kinase (AMPK) and nicotine withdrawal symptoms following chronic use. After prolonged nicotine use, the AMPK pathway in the hippocampus is activated, but this effect is quickly reversed during nicotine withdrawal.
“Increasing pAMPK levels and, consequently, downstream AMPK signaling pharmacologically attenuate anxiety-like behavior following nicotine withdrawal. We show that metformin, a known AMPK activator in the periphery, reduces withdrawal symptoms through a mechanism dependent on the presence of the AMPKα subunits within the hippocampus,” the findings state.
According to the findings, administration of the drug metaformin to laboratory rodents exposed to nicotine for two weeks resulted in the complete absence of withdrawal symptoms.
“One week of systemic metformin pretreatment resulted in activation of the AMPK pathway following nicotine withdrawal compared with saline-pretreated animals.”
“Strikingly, systemic metformin also completely prevented anxiety-like behaviors caused by nicotine withdrawal at a dose that did not impact body weight, food consumption, or glucose levels under both fed and fasted conditions.”
Given the preclinical efficacy of metformin, the results of the study indicate a possible new therapeutic target for nicotine cessation.
“Based on our findings demonstrating the preclinical efficacy of metformin in alleviating anxiety-like behavior following nicotine withdrawal, we propose that AMPK activation in the brain via metformin can be repurposed as a novel pharmacotherapy for nicotine cessation,” the authors of the study determined.
As demonstrated in this study, researchers believe that metaformin has the potential to be an effective treatment for nicotine smokers if clinical trials confirm the drug’s efficacy.