Easier to quit smoking with less upregulation of brain nicotinic acetylcholine receptors

By Will Boggs MD

NEW YORK (Reuters Health) - Smokers with less upregulation of brain nicotinic acetylcholine receptors (nAChR) are more successful at quitting than smokers with more upregulation, researchers say.

"People with predictors of poor smoking cessation outcome may need more intensive and/or lengthier treatment," Dr. Arthur L. Brody from University of California, Los Angeles told Reuters Health by email. "So, when a clinician is treating a smoker and they have predictors of poor outcome (such as more nicotine exposure or greater number of cigarettes per day), the clinician may consider moving to combinations of treatments (e.g., medication plus psychotherapy or combinations of medications) sooner and may want to plan on treating smokers for longer (e.g., more than the standard 3-4 months) in order to assist in quitting."

Several clinical variables have been shown to predict the response to smoking cessation treatments, but there have been no published studies examining brain receptor availability as a predictor.

Dr. Brody and colleagues investigated whether the degree of pretreatment nAChR upregulation (as measured by PET) in cigarette smokers is associated with smoking cessation outcomes with a standard nicotine patch taper. Eighty-one adult smokers completed the study.

Those assigned to nicotine patch treatment were significantly more likely than those assigned to placebo patch to quit smoking, and the nicotine patch group had significantly greater decreases in the number of cigarettes per day and exhaled CO levels.

Compared with nonquitters, those who successfully quit smoking had significantly less upregulation of nAChR, and this difference was not region specific. The relationship between nAChR availability and quit status did not depend on treatment group assignment.

Pretreatment nAChR availability provided additional predictive power beyond the clinical variables assessed, according to the May 21st JAMA Psychiatry online report.

"In a recent study by our group, number of cigarettes per day was found to correlate with upregulation of nAChRs in two of the brain regions studied," Dr. Brody said. "Since greater number of cigarettes per day is associated with higher daily plasma nicotine levels and also with more difficulty quitting, it is possible that plasma nicotine levels may substitute for the expensive PET scans. Also, simply knowing the number of cigarettes per day is helpful for treatment planning in cigarette smokers."

Dr. Brody added, "Regardless of whether smokers have better or worse predictors of treatment outcomes, there are many good treatments available for cigarette smoking. Even smokers who are heavily addicted and smoke three packs of cigarettes (60 cigarettes) per day or smokers who have been smoking for a many years can quit smoking. And, commonly used treatments greatly facilitate smoking cessation. Quitting smoking has been shown to (on average) prolong life even in older smokers who have been smoking for many years."

Dr. Andrew R. Tapper from the University of Massachusetts Medical School in Worcester told Reuters Health by email, "Although the phenomenon of chronic nicotine-mediated nAChR upregulation has been known for over 20 years, whether upregulation is just a biomarker of nicotine exposure or actually contributes to the behavioral manifestations of nicotine dependence is unclear and requires additional studies."

"nAChR upregulation can persist up to a month after discontinuing nicotine exposure," Dr. Tapper said. "Six to 12 weeks after quitting, nAChRs are usually close to baseline levels."

"In the future, the extent of brain nAChR upregulation may be a much more objective marker of nicotine dependence severity and treatment regimen than current methodologies," Dr. Tapper said.

SOURCE: http://bit.ly/1oqRsAa

JAMA Psychiatry 2014.

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