Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone

Clin Pharmacol Ther. 1994 Jul;56(1):86-99. doi: 10.1038/clpt.1994.105.


Objective: To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation.

Methods: This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms.

Results: The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite.

Conclusions: Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Affect / drug effects
  • Blood Pressure / drug effects
  • Breath Tests
  • Carbon Monoxide / analysis
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Mecamylamine / adverse effects
  • Mecamylamine / therapeutic use*
  • Nicotine / administration & dosage
  • Nicotine / adverse effects
  • Nicotine / therapeutic use*
  • Patient Compliance
  • Smoking Cessation / methods*
  • Substance Withdrawal Syndrome / etiology
  • Treatment Outcome


  • Mecamylamine
  • Nicotine
  • Carbon Monoxide