Derivatives from Addictive Nut Could Help Smokers Break the Nicotine Habit

Compounds derived from areca nuts could help cigarette smokers quit.

Credit: Courtesy of Roger Papke, Ph.D.

More than 480,000 people die each year in the U.S. from the effects of cigarette smoking, according to the U.S. Centers for Disease Control and Prevention. Prescription smoking cessation drugs currently on the market can work well but can also cause harmful side effects. For example, some patients taking the drug varenicline report having suicidal thoughts, sleepwalking and having cardiovascular problems.

Because of varenicline’s side effects, researchers such as Papke and Horenstein are working on alternatives at the University of Florida. Varenicline reduces nicotine cravings by binding to the same receptors that attach nicotine molecules to brain cells, but it activates those receptors to a lesser degree. Undesirable effects occur because the drug also binds to other nicotine receptors that aren’t involved in addiction, Papke explains. “The molecules that we’re developing are more specific — they do not target those other receptors at all, so our compounds should be safer,” he says.

The idea to study the areca nut came when Papke obtained a headhunter’s sword from Borneo. He learned that the peculiar carvings on its hilt might have been made by someone using betel quid. Quids are prepared by mixing sliced areca nuts with slaked lime (calcium hydroxide), spices or sweets, and in some cases tobacco, and wrapping the concoction in leaves from the betel vine. Quid chewing turns users’ teeth bright red and forces them to spit out a lot of red saliva, which discolors local sidewalks and buildings. Worse, quid use is addictive and leads to serious health effects including oral cancer and cardiovascular issues.

In prior work (watch video), Papke and Horenstein studied arecoline, one of the psychoactive alkaloids in the areca nut. They discovered that arecoline stimulates the same brain cell receptors responsible for nicotine addiction but doesn’t stimulate the other types of nicotine receptors.

Now, Horenstein is synthesizing a range of compounds with structures that are slightly different from arecoline. The researchers have found that some of these new compounds also bind to the addiction-related receptors, while leaving the other receptors alone. That means these arecoline analogs may be able to treat addiction to cigarettes or to betel quids without side effects. The next step for Horenstein and Papke is to seek funding so they can test these potential new drugs in animal trials.

The researchers acknowledge funding from the U.S. National Institutes of Health.

The researchers presented their work April 3rd at the 253rd National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting in San Francisco through Thursday. It features more than 14,000 presentations on a wide range of science topics.

Contacts and sources:
Katie Cottingham, Ph.D.
The American Chemical Society