As cigarette smoking continues to be the leading cause of preventable death in the US, as recent CDC estimates have shown, researchers have focused on tackling the biggest factor inhibiting smokers from quitting: nicotine withdrawal.
In a study, conducted at the University of Pennsylvania and Johns Hopkins University School of Medicine, researchers found that administering metformin — a first-line drug treatment for type-2 diabetes — may also lessen the symptoms of nicotine withdrawal.
The team of researchers examined the relationship between the AMP-activated protein kinase (AMPK) and withdrawal symptoms following chronic nicotine use.
The AMPK pathway located in the hippocampus is activated after prolonged use of nicotine, however, the effect can be 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 study’s author writes.
According to the findings, released in the journal PNAS, metaformin demonstrated a complete absence of withdrawal symptoms after having been administered to laboratory mice following two weeks of exposure to nicotine.
“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.”
The results of the study point researchers to a new therapeutic target for nicotine cessation, given the preclinical efficacy of metaformin.
“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.”
Researchers believe metaformin could have the potential to be a powerful treatment for nicotine smokers if clinical trials can prove the drug’s efficacy as demonstrated in the mouse study.