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Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers

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Abstract

Rationale

Clinical studies have shown that topiramate, an anticonvulsant medication, may be effective as a treatment for smoking cessation. However, less is known about topiramate effects on nicotine withdrawal and craving and its interactions with a smoked cigarette.

Objectives

The objective of this study was to investigate the effects of topiramate treatment on abstinence-related nicotine withdrawal, cue-induced cigarette craving, and the acute effects of a smoked cigarette.

Materials and methods

Fifteen female and 25 male cigarette smokers were randomly assigned to 9-day treatment with topiramate (final titration dose, 75 mg/day) or placebo. On the last day of treatment, after a 3-h smoke-free abstinence period, participants were evaluated for symptoms of nicotine withdrawal and then underwent cigarette and neutral cue reactivity testing. Thirty minutes after completing cue exposure testing, participants were then evaluated for the acute effects of a smoked cigarette. Cue reactivity and acute smoking measures included subjective ratings of cigarette craving and withdrawal and physiological measures of skin conductance and temperature, heart rate, and blood pressure. In addition, smoking topography was measured using a puff volume apparatus.

Results

Topiramate treatment enhanced subjective ratings of withdrawal after the 3-h abstinence period and reduced pre-cue skin conductance levels. Cigarette cue exposure resulted in a moderate increase in craving, which was unaffected by treatment. Topiramate treatment enhanced the rewarding effects of a smoked cigarette, even while participants smoked less per puff and achieved lower plasma nicotine levels.

Conclusion

Results suggest that topiramate enhances both nicotine withdrawal and reward. These findings question the utility of topiramate treatment for smoking cessation.

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References

  • Ängehagen M, Shank R, Hansson E, Rönnbäck L, Ben-Menacham E (2001) Topiramate affects the ability of protein kinase to phosphorylate glutamate receptors activated by kainite. Epilepsia 42(Suppl 7):S10

    Google Scholar 

  • Anthenelli RM, Blom TJ, McElroy SL, Keck PE (2006) A double-blind, placebo-controlled trial of topiramate as an aid to smoking cessation. Society for Research on Nicotine and Tobacco, 12th Annual Meeting. Orlando, FL (February 15–18, 2006)

  • Bevins RA, Besheer J, Pickett KS (2001) Nicotine-conditioned locomotor activity in rats: dopaminergic and GABAergic influences on conditioned expression. Pharmacol Biochem Behav 68:135–145

    Article  PubMed  CAS  Google Scholar 

  • Brauer LH, Behm FM, Westman EC, Patel P, Rose JE (1999) Naltrexone blockade of nicotine effects in cigarette smokers. Psychopharmacology 143:339–346

    Article  PubMed  CAS  Google Scholar 

  • Brody AL, Mandelkern MA, Lee G, Smith E, Sadeghi M, Saxena S, Jarvik ME, London ED (2004) Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study. Psychiatry Res 130:269–281

    Article  PubMed  Google Scholar 

  • 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 54:625–628

    Google Scholar 

  • Collins ED, Ward AS, McDowell DM, Foltin RW, Fischman MW (1998) The effects of memantine on the subjective, reinforcing and cardiovascular effects of cocaine in humans. Behav Pharmacol 9:587–598

    Article  PubMed  CAS  Google Scholar 

  • Cousins MS, Stamat HM, de Wit H (2001a) Acute doses of d-amphetamine and bupropion increase cigarette smoking. Psychopharmacology (Berl) 157:243–253

    Article  CAS  Google Scholar 

  • Cousins MS, Stamat HM, de Wit H (2001b) Effects of a single dose of baclofen on self-reported subjective effects and tobacco smoking. Nicotine Tob Res 3:123–129

    Article  PubMed  CAS  Google Scholar 

  • Cox LS, Tiffany ST, Christen AG (2001) Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine Tob Res 3:7–16

    Article  PubMed  CAS  Google Scholar 

  • Cummings KM, Jaen CR, Giovino G (1985) Circumstances surrounding relapse in a group of recent ex-smokers. Prev Med 195:195–202

    Article  Google Scholar 

  • Doherty K, Kinnunen T, Militello FS, Garvey AJ (1995) Urges to smoke during the first month of abstinence: relationship to relapse and predictors. Psychopharmacology (Berl) 119:171–178

    Article  CAS  Google Scholar 

  • Drobes DJ, Tiffany ST (1997) Induction of smoking urge through imaginal and in vivo procedures: physiological and self report manifestations. J Abnorm Psychol 106:15–25

    Article  PubMed  CAS  Google Scholar 

  • Durcan MJ, Deener G, White J, Johnston JA, Gonzales D, Niaura R, Rigotti N, Sachs DP (2002) The effect of bupropion sustained-release on cigarette craving after smoking cessation. Clin Ther 24:540–551

    Article  PubMed  CAS  Google Scholar 

  • Eissenberg T, Griffiths RR, Stitzer ML (1996) Mecamylamine does not precipitate withdrawal in cigarette smokers. Psychopharmacology 127:328–336

    Article  PubMed  CAS  Google Scholar 

  • Elash CA, Tiffany ST, Vrana SR (1995) Manipulation of smoking urges and affect through a brief-imagery procedure: self-report, psychophysiological, and startle probe responses. Exp Clin Psychopharmacol 3:156–162

    Article  Google Scholar 

  • Fadda P, Scherma M, Fresu A, Collu M, Fratta W (2003) Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat. Synapse 50:1–6

    Article  PubMed  CAS  Google Scholar 

  • Fattore L, Cossu G, Martellotta MD, Fratta W (2002) Baclofen antagonizes intravenous self-administration of nicotine in mice and rats. Alcohol Alcohol 37:495–498

    PubMed  CAS  Google Scholar 

  • Fiore MC, Smith SS, Jorenby D, Baker T (1994) The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA 271:1940–1947

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Hart CL, Haney M, Foltin RW, Fischman MW (2002) Effects of the NMDA antagonist memantine on human methamphetamine discrimination. Psychopharmacology 164:376–384

    Article  PubMed  CAS  Google Scholar 

  • Hatsukami DK, Hughes JR, Pickens RW, Svikis D (1984) Tobacco withdrawal symptoms: an experimental analysis. Psychopharmacology 84:231–236

    Article  PubMed  CAS  Google Scholar 

  • Hatsukami DK, Grillo M, Pentel PR, Oncken C, Bliss R (1997) Safety of cotinine in humans: physiologic, subjective, and cognitive effects. Pharmacol Biochem Behav 57(4):643–650

    Article  PubMed  CAS  Google Scholar 

  • Hughes JR (1992) Tobacco withdrawal in self-quitters. J Consult Clin Psychol 60:689–697

    Article  PubMed  CAS  Google Scholar 

  • Hughes JR, Hatsukami D (1986) Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 43:289–294

    PubMed  CAS  Google Scholar 

  • Hughes JR, Higgins ST, Hatsukami D (1990) Effects of abstinence from tobacco: a critical review. In: Kozlowski LT, Annis HM, Capell HD, Glaser FB, Goodstadt MS, Israel Y, Kalant H, Sellers EM, Vingilis ER (eds) Research advances in alcohol and drug problems, vol 10. Plenum, New York, pp 317–398

    Google Scholar 

  • Hughes JR, Gust SW, Skoog K, Keenan RM, Fenwick JW (1991) Symptoms of tobacco withdrawal: a replication and extension. Arch Gen Psychiatry 48:52–59

    PubMed  CAS  Google Scholar 

  • Hughes JR, Goldstein MG, Hurt Richard RD, Schiffman S (1999) Recent advances in the pharmacotherapy of smoking. JAMA 281:72–76

    Article  PubMed  CAS  Google Scholar 

  • Hutchinson KE, Monti PM, Rohsenow DJ, Swift RM, Colby SM, Guys M, Niaura RS, Sirota AD (1999) Effects of naltrexone with nicotine replacement on smoking cue reactivity: preliminary results. Psychopharmacology 142:139–143

    Article  Google Scholar 

  • 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 29:1465–1479

    Article  PubMed  Google Scholar 

  • Johnson BA, Ait-Daoud N, Akhtar FZ, Javors MA (2005) Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers. Arch Intern Med 165:1600–1605

    Article  PubMed  CAS  Google Scholar 

  • Johnson BA, Roache JD, Ait-Daoud N, Wells LT, Wallace CL, Dawes MA, Liu L, Wang X-Q (2006) Effects of acute topiramate dosing on methamphetamine-induced subjective mood. Int J Neuropsychopharmacol 15:1–14 (Sept)

    Google Scholar 

  • Jorenby DE, Hatsukami DK, Smith SS, Fiore MC, Allen S, Jensen J, Baker TB (1996) Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain. Psychopharmacology 128:130–138

    Article  PubMed  CAS  Google Scholar 

  • Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB (1999) A controlled trial of sustained release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 340:685–691

    Article  PubMed  CAS  Google Scholar 

  • Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR (2006) Varenicline Phase 3 Study Group. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 296:56–63

    Article  PubMed  CAS  Google Scholar 

  • Khazaal Y, Cornuz J, Bilancioni R, ZullinoDF (2006) Topiramate for smoking cessation. Psychiatry Clin Neurosci 60:384–388

    Article  PubMed  CAS  Google Scholar 

  • Kidorf M, Stitzer ML, Griffiths RR (1995) Evaluating the reinforcement value of clinic-based privileges through a multiple choice procedure. Drug Alcohol Depend 39:167–172

    Article  PubMed  CAS  Google Scholar 

  • Killen JD, Fortmann SP (1997) Craving is associated with smoking relapse: findings from three prospective studies. Exp Clin Psychopharmacol 5:137–142

    Article  PubMed  CAS  Google Scholar 

  • Killen JD, Fortmann SP, Newman B, Varady A (1991) Prospective study of factors influencing the development of craving associated with smoking cessation. Psychopharmacology 105:191–196

    Article  PubMed  CAS  Google Scholar 

  • Kuzniecky R, Ho S, Pan J, Martin R, Gilliam F, Raught E, Hetherington H (2002) Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults. Neurology 58:368–372

    PubMed  CAS  Google Scholar 

  • Levin ED, Westman EC, Stein RM, Carnahan E, Sanchez M, Herman SN, Behm FM, Rose JE (1994) Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking. J Clin Psychopharmacol 14(1):41–49

    Article  PubMed  CAS  Google Scholar 

  • Mecarelli O, Piacenti A, Pulitano P, Vicenzini E, Rizzo C, Rinalduzzi S, de Feo MR, Accornero N (2001) Clinical and electrophysiological effects of topiramate in patients with epilepsy and healthy volunteers. Clin Neuropharmacol 25:284–289

    Article  Google Scholar 

  • Miyasato K (2001) Recent advances in research on nicotine dependence and reward mechanism. Nippon Yakurigaku Zasshi 117:27–34

    PubMed  CAS  Google Scholar 

  • Mucha RF, Geier A, Pauli P (1999) Modulation of craving by cues having differential overlap with pharmacological effect: evidence for cue approach in smokers and social drinkers. Psychopharmacology 147:306–313

    Article  PubMed  CAS  Google Scholar 

  • Niaura R, Abrams DB, Monti PM, Pedraza M (1989) Reactivity to high risk situations and smoking cessation outcome. J Subst Abuse 1:393–405

    PubMed  CAS  Google Scholar 

  • Nides M, Oncken C, Gonzales D, Rennard S, Watsky EJ, Anziano R, Reeves KR (2006) Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med 166:1561–1568

    Article  PubMed  Google Scholar 

  • 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 134:233–246

    Article  PubMed  CAS  Google Scholar 

  • Patterson NE, Markou A (2002) Increased GABA neurotransmission via administration of gamma-vinyl GABA decreased nicotine self-administration in the rat. Synapse 44:252–253

    Article  CAS  Google Scholar 

  • Paterson NE, Semenova S, Gasparini F, Markou A (2003) The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice. Psychopharmacology (Berl) 167:257–264 (April 8)

    CAS  Google Scholar 

  • Payne TJ, Smith PO, Sturges LV, Holleran SA (1996) Reactivity to smoking cues: mediating roles of nicotine dependence and duration of deprivation. Addict Behav 21:139–154

    Article  PubMed  CAS  Google Scholar 

  • Perkins KA, Broge M, Gerlach D, Sanders M, Grobe JE, Cherry C, Wilson AS (2002) Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking. Health Psychol 21:332–339

    Article  PubMed  Google Scholar 

  • Perkins KA, Stitzer M, Lerman C (2006) Medication screening for smoking cessation: a proposal for new methodologies. Psychopharmacology 184:628–636

    Article  PubMed  CAS  Google Scholar 

  • Pickworth WB, Fant RV, Butschky MF, Henningfield JE (1996) Effects of transdermal nicotine delivery on measures of acute nicotine withdrawal. J Pharmacol Exp Ther 279:450–456

    PubMed  CAS  Google Scholar 

  • Physicians’ Desk Reference (PDR) (2005) Medical Economics, Montvale

  • Reid MS, Fox L, Ho LB, Berger SP (2000) Nicotine stimulation of extracellular glutamate levels in the nucleus accumbens: neuropharmacological characterization. Synapse 35:129–136

    Article  PubMed  CAS  Google Scholar 

  • Rose JE, Herskovic JE, Trilling Y, Jarvik ME (1985) Transdermal nicotine reduces cigarette craving and nicotine preference. Clin Pharmacol Ther 38:450–456

    Article  PubMed  CAS  Google Scholar 

  • Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Lane JD, Ripka GV (1994) Combined effects of nicotine and mecamylamine in attenuating smoking satisfaction. Exp Clin Psychopharmacol 4:328–344

    Google Scholar 

  • Rose JE, Behm FM, Westman EC (1998) Nicotine–mecamylamine treatment for smoking cessation: the role of pre-cessation therapy. Exp Clin Psychopharmacol 6:331–343

    Article  PubMed  CAS  Google Scholar 

  • Rose JE, Behm, FM, Westman EC, Johnson M (2000) Dissociating nicotine and non-nicotine components of cigarette smoking. Pharmacol Biochem Behav 67:71–81

    Article  PubMed  CAS  Google Scholar 

  • Rose JE, Behm FM, Westman EC (2001) Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking. Pharmacol Biochem Behav 68:187–197

    Article  PubMed  CAS  Google Scholar 

  • Rotherman-Fuller E, Shoptaw S, Newton T (2004) Safety of amantadine-baclofen combination pharmacotherapy for cocaine dependence. CPDD 2004, Symposium 3:30 PM, 6.13.04

  • Schiffer WK, Gerasimov MR, Marsteller DA, Geiger J, Barnett C, Alexoff DL, Dewey SL (2001) Topiramate selectively attenuates nicotine-induced increases in monoamine release. Synapse 42:196–198

    Article  PubMed  CAS  Google Scholar 

  • Shiffman S, Johnson JA, Khayrallah M, Elash CA, Gwalney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J (2000) The effect of buproprion on nicotine craving and withdrawal. Psychopharmacology (Berl) 148:33–40

    Article  CAS  Google Scholar 

  • Shiffman S, Shadel WG, Niaura R, Khayrallah MA, Jorenby DE, Ryan CF, Ferguson CL (2003) Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Psychopharmacology 166:343–350

    PubMed  CAS  Google Scholar 

  • Schilstrom B, Fagerquist MV, Zhang X, Hertel P, Panagis G, Nomikos GG, Svensson TH (2000) Putative role of presynaptic alpha 7 nicotinic receptors in nicotine stimulated increases of extracellular levels of glutamate and aspartate in the ventral tegmental area. Synapse 38:375–383

    Article  PubMed  CAS  Google Scholar 

  • Sofuoglu M, Poling J, Mouratidis M, Kosten T (2006) Effects of topiramate in combination with intravenous nicotine in overnight abstinent smokers. Psychopharmacology 184:645–651

    Article  PubMed  CAS  Google Scholar 

  • Sziraki I, Sershen H, Benuck M, Hashim A, Lajtha A (1998) Receptor systems participating in nicotine-specific effects. Neurochem Int 33:445–457

    Article  PubMed  CAS  Google Scholar 

  • Teneggi V, Tiffany ST, Squassante L, Milleri S, Ziviani L, Bye A (2002) Smokers deprived of cigarettes for 72 h: effect of nicotine patches on craving and withdrawal. Psychopharmacology 164(2):177–187

    Article  PubMed  CAS  Google Scholar 

  • Teneggi V, Tiffany ST, Squassante L, Milleri S, Ziviani L, Bye A (2005) Effect of sustained-release (SR) bupropion on craving and withdrawal in smokers deprived of cigarettes for 72 h. Psychopharmacology 183(1):1–12

    Article  PubMed  CAS  Google Scholar 

  • Thuerauf N, Lunkenheimer J, Lunkenheimer B, Sperling W, Bleich S, Schlabeck M, Wiltfang J, Kornhuber J (2007) Memantine fails to facilitate partial cigarette deprivation in smokers—no role of memantine in the treatment of nicotine dependency. J Neural Transm 114:351–357

    Article  PubMed  CAS  Google Scholar 

  • Tiffany ST, Drobes DJ (1991) The development and initial validation of a questionnaire on smoking urges. Br J Addict 86:1467–1476

    Article  PubMed  CAS  Google Scholar 

  • Tiffany ST, Cox LS, Elash CA (2000) Effects of transdermal nicotine patches on abstinence-induced and cue-elicited craving in cigarette smokers. J Consult Clin Psychol 68:233–240

    Article  PubMed  CAS  Google Scholar 

  • West R, Shiffman S (2001) Effect of oral nicotine dosing forms on cigarette withdrawal symptoms and craving: a systematic review. Psychopharmacology 155:115–122

    Article  PubMed  CAS  Google Scholar 

  • Westman EC, Levin ED, Rose JE (1992) Smoking while wearing the nicotine patch: is smoking satisfying or harmful? Clin Res 40:871A

    Google Scholar 

  • Westman EC, Behm FM, Simel DL, Rose JE (1997) Smoking behavior on the first day of a quit attempt predicts long-term abstinence. Arch Intern Med 157:335–340

    Article  PubMed  CAS  Google Scholar 

  • White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH (1997) Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res 28:167–179

    Article  PubMed  CAS  Google Scholar 

  • Zona C, Ciotti MT, Avoli M (1997) Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells. Neurosci Lett 231:123–126

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by NIDA grant R21 DA017556 (MS Reid). All experiments were approved by the Institutional Review Board of New York University School of Medicine and the VA New York Harbor Healthcare System. None of the authors have any financial interest with the study sponsor or the study medication. We wish to thank Tom Cooper, Jed Rose, Deborah Leon, and Pooja Paunikar for their support in this study.

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Authors and Affiliations

  1. Department of Psychiatry, New York University School of Medicine, New York, NY, USA

    Malcolm S. Reid, Joseph Palamar, Sumithra Raghavan & Frank Flammino

  2. VA New York Harbor Healthcare System, 116A, 423 E. 23rd Street, New York, NY, 10010, USA

    Malcolm S. Reid

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  1. Malcolm S. Reid
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  2. Joseph Palamar
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  3. Sumithra Raghavan
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Correspondence to Malcolm S. Reid.

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Reid, M.S., Palamar, J., Raghavan, S. et al. Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers. Psychopharmacology 192, 147–158 (2007). https://doi.org/10.1007/s00213-007-0755-6

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