A class of drugs used to improve cognitive impairment from Alzheimer’s disease may potentially help people to permanently quit smoking, a new study suggests.
Despite several safe drug therapies available to help smokers quit, three-quarters report relapsing within six months of a quit attempt, researchers said.
Researchers from the University of Pennsylvania saw potential for a permanent cessation solution in a class of US Food and Drug Administration (FDA)-approved medications used to improve cognitive impairment from Alzheimer’s disease.
In a study consisting of a rat trial and a human trial, researchers studied the effects of two acetylcholinesterase inhibitors, or AChEIs, called galantamine and donepezil on overall nicotine intake.
The rat component showed that pretreating the rodents with an AChEI decreased their nicotine consumption.
Consistent with these effects, clinical trial participants taking the AChEI, not the placebo, smoked 2.3 fewer cigarettes daily, a 12 per cent decrease, and noted feeling less satisfied with the cigarettes they did smoke.
“We’re very interested in screening potential efficacy of anti-addiction medications in our models,” said Heath Schmidt, a professor in Penn’s School of Nursing and Perelman School of Medicine.
“For this study, we looked at potential smoking-cessation medications,” said Schmidt.
Specifically, research from Caryn Lerman, director at Penn’s Centre for Interdisciplinary Research on Nicotine Addiction (CIRNA), concluded that people who quit smoking often report a decrease in what is commonly called their executive functions.
“They feel fuzzy. They are forgetful. Those deficits are related to their ability to quit smoking. It was this clinical aspect of smoking cessation we thought would be useful to take further,” said Rebecca Ashare, a professor in Penn Medicine’s psychiatry department.
That is when they turned to the acetylcholinesterase inhibitors.
In the brain, the neurotransmitter called acetylcholine is important to cognitive functions like learning and short-term memory.
When nicotine enters the body, it binds to the same receptors in the brain that acetylcholine binds to, resulting in smoking’s rewarding and reinforcement effects.
Acetylcholinesterase inhibitors increase acetylcholine levels in the brain and, in effect, substitute nicotine’s effects.
Schmidt had successfully employed such a model with other addictive substances like cocaine. He divided a group of rats into galantamine and donepezil cohorts.
To mirror voluntary drug taking in humans, the rats self-administered nicotine using a lever pushed at will. Once nicotine-taking stabilised, the rats were pretreated with one of the two AChEIs.
For both drugs, “we were able to show a reduction in total nicotine self-administered,” Schmidt added.
The study was published in the Nature journal Translational Psychiatry.