Abstract
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.
Similar content being viewed by others
References
CDC (Center for Disease Control) (2005) Annual smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 1997–2001. MMWR Morb Mortal Wkly Rep 54(25):625–628
Cheseaux M, Monnat M, Zullino DF, Cottier AC, Besson J (2003) Topiramate in benzodiazepine withdrawal. Hum Psychopharmacol 18(5):375–377
Cryan JF, Bruijnzeel AW, Skjei KL, Markou A (2003) Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat. Psychopharmacology 168(3):347–358
Fiore M (2000) Tobacco use and dependence guideline panel. Treating tobacco use and dependence. U.S. Department of Health and Human Services, USA
Gibbs JW III, Sombati S, DeLorenzo RJ, Coulter DA (2000) Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia 41(Suppl 1):S10–S16
Golden C (1978) Stroop color and word test: a manual for clinical and experimental uses. Stoelting Company, Wood Dale
Gordey M, DeLorey TM, Olsen RW (2000) Differential sensitivity of recombinant GABA(A) receptors expressed in Xenopus oocytes to modulation by topiramate. Epilepsia 41(Suppl 1):S25–S29
Gourlay SG, Benowitz NL (1997) Arteriovenous differences in plasma concentration of nicotine and catecholamines and related cardiovascular effects after smoking, nicotine nasal spray, and intravenous nicotine. Clin Pharmacol Ther 62(4):453–463
Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 86:1119–1127
Henningfield JE, Miyasato K, Jasinski DR (1985) Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine. J Pharmacol Exp Ther 234(1):1–12
Herrero AI, Del Olmo N, Gonzalez-Escalada JR, Solis JM (2002) Two new actions of topiramate: inhibition of depolarizing GABA(A)-mediated responses and activation of a potassium conductance. Neuropharmacology 42(2):210–220
Hughes JR (1996) Treating smokers with current or past alcohol dependence. Am J Health Behav 20(5):286–290
Hughes JR, Hatsukami D (1986) Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 43(3):289–294
Hughes JR, Hatsukami DK (1997) Effects of three doses of transdermal nicotine on post-cessation eating, hunger and weight. J Subst Abuse 9151–9159
Hukkanen J, Jacob P III, Benowitz NL (2005) Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57(1):79–115
Hurt RD, Offord KP, Croghan IT, Gomez-Dahl L, Kottke TE, Morse RM, Melton LJ III (1996) Mortality following inpatient addictions treatment. Role of tobacco use in a community-based cohort. JAMA 275(14):1097–1103
Johnson BA (2004) Topiramate-induced neuromodulation of cortico-mesolimbic dopamine function: a new vista for the treatment of comorbid alcohol and nicotine dependence? Addict Behav 29(7):1465–1479
Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ (2003) Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 361(9370):1677–1685
Johnson BA, Ait-Daoud N, Akhtar FZ, Javors MA (2005) Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers: a randomized controlled trial. Arch Intern Med 165(14):1600–1605
Jones HE, Garrett BE, Griffiths RR (1999) Subjective and physiological effects of intravenous nicotine and cocaine in cigarette smoking cocaine abusers. J Pharmacol Exp Ther 288(1):188–197
Kampman KM, Pettinati H, Lynch KG, Dackis C, Sparkman T, Weigley C, O’Brien CP (2004) A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend 75(3):233–240
Kuzniecky R, Ho S, Pan J, Martin R, Gilliam F, Faught E, Hetherington H (2002) Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults. Neurology 58(3):368–372
Lee S, Sziklas V, Andermann F, Farnham S, Risse G, Gustafson M, Gates J, Penovich P, Al-Asmi A, Dubeau F, Jones-Gotman M (2003) The effects of adjunctive topiramate on cognitive function in patients with epilepsy. Epilepsia 44(3):339–347
Mancuso G, Warburton DM, Melen M, Sherwood N, Tirelli E (1999) Selective effects of nicotine on attentional processes. Psychopharmacology (Berl) 146(2):199–204
McNair D, Lorr M, Dropperman L (1971). Manual for profile of mood states. Educational and Industrial Testing Services, San Diego
Medical Economics Data (2005) Physicians desk reference. Medical Economics Data, Montvale
Meyer JH, Goulding VS, Wilson AA, Hussey D, Christensen BK, Houle S (2002) Bupropion occupancy of the dopamine transporter is low during clinical treatment. Psychopharmacology (Berl) 163(1):102–105
Okada M, Yoshida S, Zhu G, Hirose S, Kaneko S (2005) Biphasic actions of topiramate on monoamine exocytosis associated with both soluble N-ethylmaleimide-sensitive factor attachment protein receptors and Ca(2+)-induced Ca(2+)-releasing systems. Neuroscience 134(1):233–246
Provost SC, Woodward R (1991) Effects of nicotine gum on repeated administration of the Stroop test. Psychopharmacology (Berl) 104(4):536–540
Reeves D, Winter K, Kane R, Elsmore T, Bleiberg J (2001) ANAM. User’s manual. National Cognitive Recovery Foundation, San Diego
Rose JE, Behm FM, Westman EC, Coleman RE (1999) Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend 56(2):99–107
Salinsky MC, Storzbach D, Spencer DC, Oken BS, Landry T, Dodrill CB (2005) Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology 64(5):792–798
Silagy C, Lancaster T, Stead L, Mant D, Fowler G (2004) Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3 (http://DOI.10.1002/14651858.CD000146.pub2)
Tatum WO IV, French JA, Faught E, Morris GL III, Liporace J, Kanner A, Goff SL, Winters L, Fix A (2001) Postmarketing experience with topiramate and cognition. Epilepsia 42(9):1134–1140
White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH (2000) Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia 41(Suppl 1):S17–S20
Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M (2004) A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes Relat Metab Disord 28(11):1399–1410
Zullino DF, Cottier AC, Besson J (2002) Topiramate in opiate withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 26(6):1221–1223
Acknowledgements
This research was supported by the National Institute on Drug Abuse grants P50-DA12762, K05-DA0454 (TRK), R01-DA 14537, and K12 00167 (MS). We would like to thank the Biostudies nursing staff for technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sofuoglu, M., Poling, J., Mouratidis, M. et al. Effects of topiramate in combination with intravenous nicotine in overnight abstinent smokers. Psychopharmacology 184, 645–651 (2006). https://doi.org/10.1007/s00213-005-0296-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-005-0296-9