The mesolimbic
dopamine system is thought to be a critical substrate for drugs of addiction including
nicotine. Since
dopamine may play a critical role in mediating the reinforcing effects of
nicotine, we hypothesized that administering
levodopa in its therapeutic form (
carbidopa/levodopa) might be effective for smoking cessation by replacing the effects of
dopamine that smokers may seek during smoking. A pilot open-label study using
carbidopa/levodopa for smokers wanting to stop smoking was carried out at the Mayo Clinic
Nicotine Research Center, Rochester, MN. The dosing schedule was one
tablet TID for 1 week, 1 1/2
tablets TID for 1 week, then two
tablets TID for 6 weeks. Each
tablet contained 25 mg of
carbidopa and 100 mg of
levodopa. The subjects were 40 adult smokers smoking > or = 20 cigarettes per day for 3 or more years. Self-reported abstinence from smoking was confirmed by expired air CO level of < or = 8 ppm.
Nicotine withdrawal symptoms were assessed at baseline and daily during the medication phase. Smoking abstinence rates and
withdrawal symptom relief were compared to the placebo (n = 153) arm of a previously reported
bupropion smoking cessation trial. The biochemically confirmed, 7-day point-prevalence smoking abstinence rate at the end of
carbidopa/levodopa treatment was 20.0% versus 19.0% for the placebo group (p > 0.10), and 12.5% of the
carbidopa/levodopa group were abstinent versus 15.7% for the placebo group (p > 0.10) at 6 months. Subjects from both studies had significant increases in withdrawal scores from baseline, but there were no significant differences between the two groups at any time period. We found no differences in smoking abstinence rates or
nicotine withdrawal symptom relief in smokers receiving
carbidopa/levodopa compared to placebo. Despite the theoretical reasons why
carbidopa/levodopa might be effective as a pharmacological adjunct in treating smokers, it was not observed in this group of smokers at this dose.