Certain people are far more vulnerable to nicotine addiction than others, and this is most likely due to genetic and metabolic differences, say scientists at Johns Hopkins University.
Their study, which traced the earliest steps of nicotine “reinforcement” in a sample of 18 adults who had never smoked, found that some people are clear nicotine “choosers” while others are nicotine “avoiders.”
“From an addiction point of view, nicotine is a very unusual drug,” said addiction researcher Roland R. Griffiths, Ph.D., 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.”
“Our results suggest there are definitely some people who are nicotine avoiders and others who are nicotine choosers,” he said, “and there are probably genetic or metabolic vulnerabilities that make people fall into one group or the other.”
The researchers, whose findings are published in the journal Psychopharmacology, say that they have, for the first time, characterized the body’s reaction to the first, tiniest “hits” of nicotine.
The discovery may lay the groundwork for future research focusing on genetic or other biological factors that make people vulnerable to nicotine addiction.
“Scientists have struggled for decades to understand why, in the face of initial dislike, so many people become addicted to cigarettes,” said Griffiths.
Prior research, for example, has found 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 a nicotine-containing pill, gum, or candy, or a placebo (a classic test of the “reinforcement” abilities of an addictive drug), still choose the placebo.
Similarly, even in laboratory mice and rats, nicotine usually fails the reinforcement test, with animals choosing a placebo over nicotine.
To find an answer to this puzzling question, the researchers set out to explore the conditions under which nicotine’s reinforcement properties first take hold in never-smokers.
Instead of offering a dose of nicotine similar to that in a cigarette or in a nicotine patch or gum — doses that can overwhelm first-time users — his team used doses about 10 times lower, barely above what is needed for someone to notice nicotine’s effects, such as relaxation, jitters, better focus, energy, or changes in mood.
Then the researchers designed a double-blind study in which volunteers wouldn’t know whether they were getting nicotine or a placebo.
“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.
They recruited 18 healthy men and women who had never smoked — or only ever smoked a handful of cigarettes — and gave each of them two identical-looking pills labeled A and B each day for several weeks. The subjects were told the pills might contain any of a number of substances, ranging from caffeine or sugar, to ginseng, chamomile, theobromine, kava, or nicotine.
The order of the pills was changed across days. Volunteers were asked to report their symptoms — relaxation, changes in energy levels, concentration, light-headedness, drowsiness, and jitters — after each pill.
Finally, the participants were given a choice of taking either pill and asked to explain their decision. Some participants thought the placebo contained a drug — one that made them drowsy, for instance — so they weren’t necessarily choosing one they thought didn’t cause symptoms.
Exactly half of the participants reliably chose the nicotine pill, citing improved concentration, alertness, stimulation, energy, and better mood. The other half, however, 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.
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.”
Source: Johns Hopkins Medicine