Individuals with a specific genetic mutation -- called CYP2A6 -- appear to be especially resistant to nicotine addiction. Now, researchers report that a compound that mimics the effect of this gene could help smokers kick the habit.

The compound -- called methoxsalen -- ``could be part of a (smoking) cessation or smoking reduction program,'' conclude Dr. Edward Sellars and colleagues at Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario. They presented the findings here at the 68th annual meeting of The Royal College of Physicians and Surgeons of Canada. In an interview with Reuters Health, Sellars explained that ''individuals with CYP2A6 mutations metabolize nicotine more slowly and, if (nicotine) dependent, smoke fewer cigarettes.'' His team of researchers discovered that methoxsalen -- a drug used to treat psoriasis -- effectively inhibits an enzyme produced by the CYP2A6 gene. This finding led them to speculate that methoxsalen might mimic the effects of CYP2A6, inhibiting nicotine metabolism and reducing the smoker's urge to smoke. In four separate studies, the investigators recruited between 7 to 17 smokers and gave them nicotine in combination with either methoxsalen or a 'dummy' placebo. As expected, they found that methoxsalen reduced levels of (metabolised) blood nicotine by more than 75% compared with placebo. ``This demonstrated... inhibition of CYP2A6 nicotine metabolism,'' Sellers commented. Subjects were then asked to refrain from smoking for 60 minutes, and were again given methoxsalen along in combination with nicotine. The result? Over the next 90 minutes, methoxsalen therapy reduced the number of cigarettes smoked by 24%, according to the Toronto team. They also noted that levels of carbon monoxide in the study participant's breath fell by 47% -- an indicator that smokers took shallower puffs than before using methoxsalen. ``Smoking is a very regulated behavior and people smoke in order to get a certain amount of nicotine into the body,'' Sellers explained. If nicotine is more slowly metabolized, people start to feel dizzy or sick, ``so they won't oversmoke,'' he said. He added that methoxsalen also appears to inhibit the activation of certain carcinogenic compounds found in tobacco smoke, a finding that suggests the compound may help to reduce cancer risk.

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