Addiction risk differs with tiny nicotine ‘hits’

"From an addiction point of view, nicotine is a very unusual drug," says Roland R. Griffiths. "When you give people nicotine for the first time, most people don't like it." (Credit: iStockphoto)

Some first-time users of even small doses of nicotine are far more vulnerable to addiction than others, a study of nonsmokers demonstrates.

The researchers say they have described the body’s reaction to the first, tiniest “hits” of nicotine. The results, they say, should lay groundwork for future revelations about genetic or other biological factors that make people vulnerable to nicotine addiction.

“Our results suggest there are definitely some people who are nicotine avoiders and others who are nicotine choosers,” lead investigator Roland R. Griffiths says, “and there are probably genetic or metabolic vulnerabilities that make people fall into one group or the other.”

A summary of the research appears online in the journal Psychopharmacology.

‘A very unusual drug’

Scientists have struggled for decades to understand why, in the face of initial dislike, so many become addicted to cigarettes.

“From an addiction point of view, nicotine is a very unusual drug,” says Griffiths, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “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.”

Previous research has shown that a majority of never-smokers given a cigarette or dose of nicotine dislike the effects. It also shows that later, when offered a nicotine-containing pill, gum, or candy, or a placebo—a classic test of the “reinforcement” abilities of an addictive drug—they choose the placebo.

Tiny doses and placebos

Griffiths and his team set out to explore the conditions under which nicotine’s reinforcement properties do first take hold in some never-smokers.

Rather than use a dose of nicotine similar to that in a cigarette, nicotine patch, or gum—doses that can overwhelm first-time users—his team used doses barely above what is needed for someone to notice nicotine’s effects, such as relaxation, jitters, better focus, energy, or changes in mood. The researchers designed a double-blind study in which volunteers wouldn’t know when they were getting nicotine or a placebo.

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“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,” Griffiths says.

Eighteen healthy men and women who had never smoked—or never smoked more than a handful of cigarettes—received two identical-looking pills labeled A and B each day for several weeks. The volunteers were told the pills might contain any of a number of substances, ranging from caffeine or sugar, to ginseng, chamomile, theobromine, kava, or nicotine.

Which pill do you prefer?

In fact, each day, each volunteer was given one very-low-dose nicotine pill and one placebo. The order of the pills was mixed across days. Volunteers reported their symptoms—relaxation, changes in energy levels, concentration, light-headedness, drowsiness, and jitters—after each pill.

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Then, on at least 10 successive days, they 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 reliably distinguish between mystery pill A and mystery pill B, the dose of nicotine was increased slightly. Once each volunteer could reliably distinguish between pill A and B, they were given a choice of taking either pill and asked to explain their decision.

Nine of the 18 participants chose the placebo, often explaining that the nicotine pill—although they didn’t know it contained nicotine—made them feel light-headed, dizzy, or sick. The other half, however, reliably chose the nicotine pill, citing improved concentration, alertness, stimulation, energy, and better mood.

Griffiths believes this is the first study to conclusively show that nicotine can pass the reinforcement test in never-users, and he expects it will inform future studies of “avoiders” and “choosers.” Ultimately, he says, “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.”

Additional authors of the study are from Johns Hopkins and the Wake Forest School of Medicine.

The National Institute on Drug Abuse supported the work.

Source: Johns Hopkins University