Current Research and Scholarly Interests
Drug addictions are viewed as chronic, relapsing disorders that may require extended therapy and follow-up. However, very few smoking cessation trials have examined the utility of extended therapy models. In a recently completed trial we attempted to boost long-term abstinence rates by extending the course of therapy. 362 adult smokers received 11 weeks of therapy that combined nicotine replacement, bupropion and behavioral therapy followed by an additional 14 weeks of therapy with bupropion or matching placebo. 52% were abstinent at 11 weeks. This result is almost double the mean treatment response (27%) typically observed for nicotine patch therapy. The overall abstinence rate at 25 weeks was about 40%, nearly twice the 24-week follow-up response observed in nicotine patch studies (21%). Abstinence percentages at week 52 (30%+) also represent a better-than-average treatment response.
We are now conducting a randomized clinical trial to examine the efficacy of a selegiline transdermal system in promoting cigarette smoking cessation.This is the first trial to examine this medication, developed as a treatment for Parkinsons disease, as a possible therapy for nicotine dependence. We are interested in selegiline as a smoking cessation therapy because this medication potentiates dopamine through inhibition of MAO-B. Our interest in this medication derives from evidence suggesting that (1) the positive reinforcing effects of addictive drugs play an important role in maintaining drug use; (2) facilitation of dopaminergic neurotransmission in the mesocorticolimbic dopamine system appears to be critical for the acute reinforcing actions of stimulant drugs including nicotine and (3) the craving which produces relapse reflects memory of dopamine- mediated positive reinforcement. The choice of selegiline is based on the rationale that a medication that can potentiate dopamine may thus help to alleviate craving to take a drug for its positive reinforcing effects.
Finally, we are exploring genetic factors that may influence response to treatment. In each of the studies described above smokers are genotyped for polymorphisms at loci hypothesized to affect nicotine dependence and/or treatment efficacy to determine if polymorphisms at these loci affect relapse rate in smokers.