In adjacent rooms at Penn’s Center for Interdisciplinary Research on Nicotine Addiction (CIRNA) in the Perelman School of Medicine, a man flips through a magazine, and a woman fiddles with her phone. Both have easy access to cigarettes should they want one, and both have researchers watching whether they decide to smoke.

These scenarios are part of ongoing trials at CIRNA, where Rebecca Ashare, a research assistant professor of psychology in psychiatry at Penn Medicine, conducted work she and several Penn colleagues recently published in the journal Translational Psychiatry.

The research aims to repurpose an FDA-approved drug called galantamine currently used to improve cognitive function in Alzheimer’s patients. If successful, it could help tobacco smokers quit, and preliminary results look favorable: In Ashare’s initial trial of 33 adults age 18 to 60, participants smoked 2.3 fewer cigarettes daily and reported less satisfaction with those they did.

Previous CIRNA research showed that people who attempt smoking cessation often experience decreased cognitive function.

“Some smokers report that this is what causes them to relapse,” says Heath Schmidt, senior author of the paper who has appointments in the School of Nursing and Penn Medicine. “We were interested in whether these cognitive-enhancing compounds, called acetylcholinesterase inhibitors (AChEI), would reduce nicotine use.”

Acetylcholine is a neurotransmitter that plays an important role in cognitive functions; nicotine that enters the body binds to its receptors in the brain, resulting in smoking’s rewards and reinforcement. An AChEI such as galantamine essentially aims to increase this neurotransmitter.

“We’re hoping that by enhancing levels of acetylcholine with the cholinesterase inhibitors, smokers may not need to smoke as much,” Ashare says. In other words, this would artificially simulate comparable effects to smoking, but do so without nicotine.

Schmidt first proved this theory with an experiment during which rats self-administered nicotine. After the animals received galantamine or another AChEI called donepezil, they consumed less nicotine.

Nausea and vomiting are common side effects of AChEIs, but rats lack the vomiting reflex. To ensure that the animals didn’t intake less nicotine simply because they felt sick, Schmidt provided kaolin clay, which coats the stomach and can become an indicator of their malaise. The rats didn’t ingest more clay, indicating the AChEI treatment didn’t make them ill. 

Ashare then translated the hypothesis into a human trial to answer two questions: Does galantamine reduce cognitive deficits often associated with quitting smoking? And if it does, can it improve someone’s chances of quitting permanently?

Participants, who smoked for the majority of the trial, took galantamine or a placebo and completed three assessments. Then, during a weeklong “monitored abstinence” period, researchers asked participants to “try their best” not to smoke, Ashare says. “If you can quit for those first seven days, you are 32 times more likely to be smoke-free at the end of treatment.”

The study found that galantamine-taking participants reduced the number of cigarettes smoked by 2.3 cigarettes per day (12 percent) compared to 1.3 cigarettes (7 percent) in the placebo group. They also got less reward from their puffs.

“This is all really promising,” Ashare says. “If people are smoking less and they don’t enjoy their cigarettes as much, we hope this will lead to better quit rates.”