Study shows how nicotine reinforces effects in first-time smokers

New research revealed for the first time how nicotine begins to lull susceptible people into an addiction to smoking, according to a study published September 8, 2015 in Psychopharmacology.

“From an addiction point of view, nicotine is a very unusual drug,” said lead investigator and addiction researcher Roland R. Griffiths, PhD, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine in Baltimore, MD. “When you give people nicotine for the first time, most people don’t like it. It’s different from many other addictive drugs, for which most people say they enjoy the first experience and would try it again.”

That response to a stimulus and the likelihood to try it again is referred to as reinforcement. While nicotine is certainly addictive, nicotine’s power of reinforcement is inconsistent and has never been demonstrated in people who are brand new to smoking.

Previous research has shown that a majority of never-smokers who are given a cigarette or dose of nicotine not only report disliking the effects, but later, when offered the choice of a placebo or a nicotine-containing pill, gum, or candy—a classic test of the “reinforcement” abilities of an addictive drug—they chose the placebo. Even in laboratory experiments, mice and rats generally chose a placebo over nicotine.

In this study, the researchers sought to determine the conditions under which nicotine’s reinforcement properties first take hold in never-smokers. They recruited 18 healthy men and women who had never smoked (or only smoked a handful of cigarettes in their lifetimes) and gave each of them two identical-looking pills labeled A and B each day for several weeks. Researchers told the subjects that the pills might contain any of a number of substances, including caffeine, sugar, ginseng, chamomile, theobromine, kava, or nicotine.

In actuality, each volunteer was given one very-low-dose nicotine pill (starting at 1.5 mg of nicotine per 70 kg of body weight) and one placebo, with at least two hours between pills. The order of the pills was mixed across days. Volunteers were asked to report their symptoms—such as relaxation, changes in energy levels, concentration, light-headedness, drowsiness, and jitters—after each pill.

A regular cigarette has a dose of nicotine that can overwhelm a first-time user, so investigators began with a dose about 10 times lower, just barely enough for subjects to notice the drug’s effects. “We attempted to develop conditions in which people could learn to become familiar with the subtle mood-altering effects of very low doses of nicotine, with the goal of uncovering the reinforcing effects of nicotine,” Dr. Griffiths said.

On 10 successive days, subjects were given the same pills again, this time unlabeled, and asked to identify which pill was A and which was B. If the volunteer was unable to distinguish between the two pills, the investigators slightly increased the dose of nicotine. Once each person could reliably distinguish between pill A and pill B, subjects were given a choice of taking either pill and asked to explain why they chose it.

Half of the participants (9 of 18) reliably chose the nicotine pill, citing positive subjective effects such as improved concentration, alertness, stimulation, energy, and better mood. The other half chose the placebo, predominantly reporting that the other pill—which they didn’t know contained nicotine—produced negative effects such as feelings of light-headedness, dizziness, or upset stomach.

This is the first study to conclusively show that nicotine can pass the reinforcement test in never-users, the researchers concluded. They expect it will inform future studies of “avoiders” and “choosers.”

In addition, Dr. Griffith said, “I hope our findings will point the way toward future interventions that prevent or treat nicotine addiction, a topic of increasing importance in light of the expanding marketing of electronic nicotine delivery devices—e-cigarettes—to youthful nicotine nonusers.”