Effects of topiramate in combination with intravenous nicotine in overnight abstinent smokers

Psychopharmacology (Berl). 2006 Mar;184(3-4):645-51. doi: 10.1007/s00213-005-0296-9. Epub 2006 Jan 24.


Rationale: Topiramate, an anticonvulsant medication, may be effective as a treatment for alcohol and cocaine addiction. While a recent clinical study has demonstrated the potential utility of topiramate for smoking cessation in alcohol-dependent smokers, the effects of topiramate on tobacco addiction have not been systematically examined in humans.

Objectives: To determine topiramate's effects on acute physiological and subjective responses to intravenous (IV) nicotine in overnight abstinent smokers.

Methods: Seven male and five female smokers participated in a double-blind, placebo-controlled, crossover study, which consisted of one adaptation and three experimental sessions. Before each session, participants were treated orally with either a single 25 or 50 mg topiramate dose or with placebo. Starting 2 h following the medication treatment, participants received an IV saline injection, followed by 0.5 and 1.0 mg/70 kg IV nicotine.

Results: Topiramate treatment at 50 mg, compared to 25 mg or placebo, attenuated heart rate increases induced by nicotine. Topiramate, compared to placebo, enhanced the ratings of subjective effects from nicotine including "drug strength," "good effects," "head rush," and "drug liking." Topiramate treatment did not affect performance on the Stroop test.

Conclusions: These results suggest that topiramate may enhance the subjective effects of nicotine and attenuate the heart rate response to nicotine. While the exact mechanisms are unclear, enhancement of the dopaminergic system and attenuation of the noradrenergic system may mediate the topiramate's effects on the subjective and cardiovascular responses to nicotine, respectively. The utility of topiramate for smoking cessation needs to be examined further in controlled clinical trials.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Arousal / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use
  • Heart Rate / drug effects
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Nicotine / adverse effects*
  • Nicotine / therapeutic use*
  • Smoking Cessation / methods*
  • Smoking Cessation / psychology
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / psychology
  • Tobacco Use Disorder / diagnosis
  • Tobacco Use Disorder / psychology
  • Tobacco Use Disorder / rehabilitation*
  • Topiramate


  • Topiramate
  • Fructose
  • Nicotine