Combined Agonist-Antagonist Treatment for Nicotine and Other Drug Dependencies

Abstract

Co-administration of an agonist with an antagonist may regulate receptor activation, resulting in relief of withdrawal symptoms and blockade of drug reward. In one study, 12 smokers rated the rewarding effects of cigarette smoke after separate and combined administration of nicotine and the nicotinic antagonist mecamylamine. While each drug offset potential side effects of the other, they acted in unison to attenuate smoking reward. In a second study, 48 subjects participated in a randomized, double-blind, placebo-controlled smoking cessation trial. Nicotine skin patch therapy (21 mg/day for 6-8 weeks) + oral mecamylamine (2.5-5 mg b.i.d. for 5 weeks) was compared to nicotine patch + placebo. Mecamylamine treatment began two weeks before smoking cessation. Combined agonist-antagonist treatment produced significantly higher continuous smoking abstinence than agonist-alone treatment: 50% vs 16.7% at seven weeks (p=.015), 37.5% vs 12.5% at six months (p=.046) and 37.5% vs 4.2% at twelve months (p=.004). Concurrent agonist-antagonist treatment may prove useful in treating other drug dependencies, and has potential advantages over treatment using agonists alone, antagonists alone or partial agonists.