Clinical evaluation of mecamylamine for withdrawal from nicotine dependence

Mecamylamine (MCL) has been shown to extinguish nicotine dependence in rats and monkeys. MCL was administered to fourteen nicotine-dependent persons to determine if it may be effective in withdrawing nicotine-dependent humans at doses which have acceptable toxicity. Subjects smoked 20 to 60 cigarettes per day for a mean of 2.4 years, and none had been nicotine abstinent for as much as one day for at least one year. MCL was started in a dose of 5 to 10 mg per day and progressively raised until the subject experienced nicotine blockage and/or toxic effects. During MCL administration, 7 of 14 (50%) totally ceased smoking within the first 11 days of treatment, and an additional 4 (28.6%) subjects reduced cigarette consumption to less than five per day by the end of three weeks. Thirteen of 14 (92.9%) subjects stated that MCL blocks nicotine, reduces nicotine craving, and "works." At least some minor side-effects of MCL were observed in every subject. The most intolerable side-effects were constipation, urinary retention, abdominal cramps, and weakness, and these were responsible for drop-out of 5 (35.7%) subjects. Although there is a high prevalence of side-effects, MCL is probably a viable withdrawal treatment for some cases of recalcitrant nicotine dependence.