What makes nicotine so addictive? The answer to that question could help researchers develop a drug that would help smokers give up cigarettes for good.

A study published online this week provides some useful clues. Researchers zeroed in on a particular gene called OPRM1. This gene contains instructions for building a type of receptor that allows opioids – including drugs like heroin and morphine as well as opioids produced inside the body – to make their presence known in the brain, triggering release of the feel-good chemical dopamine. Nicotine prompts the body to produce more of its own opioids, which in turn releases more dopamine.

At a particular location on the OPRM1 gene, many people inherit an A (short for adenine) from both parents. But some people inherit a G (short for guanine) from at least one parent. That small difference can affect whether smokers become addicted to nicotine – and the cigarettes that contain them.

So researchers from the University of Pennsylvania and colleagues recruited 12 smokers with the common A/A version of the gene and 10 smokers with at least one G in the crucial spot. All were asked to abstain from smoking overnight. Then they were given a cigarette and examined with an imaging technology called positron emission tomography, or PET, which allows researchers to track biological function inside the brain. (Each of the smokers did the test twice – once with a real cigarette and once with a dummy cigarette that contained no nicotine, though they weren’t told which was which.)


It turned out that a lot more was going on in the brains of smokers with the A/A version of the gene. After smoking the real cigarette, the opioid receptors in their brains were a lot more active than they were in smokers with a G version of the gene. The researchers don’t know why that small genetic change made such a marked difference. But they added that their observations are consistent with prior studies – in mice – that found that having a G version of the gene made nicotine less appealing and easier to give up compared with having the A/A version of the gene.

The researchers called the study “a critical first step” to figuring out the biological link between different version of the gene and smoking behavior. The findings may also shed light on addiction to other types of drugs, they said.

The study was published by the Proceedings of the National Academy of Sciences.

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