Skip to main content
SpringerLink
Log in

Randomized, controlled, double-blind trial of taranabant for smoking cessation

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

It has been proposed that cannabinoid-1 receptor inverse agonists might be effective for smoking cessation. We evaluated this hypothesis with the cannabinoid-1 receptor inverse agonist taranabant.

Methods

Adults who smoked ≥10 cigarettes a day for >1 year and had an expired CO level of ≥10 ppm participated in a randomized, double-blind, 8-week, study of taranabant (N = 159) or placebo (N = 158). Taranabant was titrated from 2 mg once daily to 8 mg once daily. Patients received smoking cessation counseling. The primary efficacy endpoint was continuous abstinence, defined as no cigarettes assessed by daily patient self-report and verified by breath CO level (<10 ppm) and plasma cotinine test (<10 ng/ml), during the last 4 weeks of the 8-week treatment period.

Results

The percentage of patients achieving continuous abstinence was 7.5% for taranabant 2–8 mg and 6.3% for placebo (odds ratio = 1.2 [90% confidence interval (CI), 0.6, 2.5], P = 0.678). Change from baseline in body weight in the taranabant 2–8-mg group was −1.5 (90% CI, −1.8, −1.3) versus 0.6 kg (90% CI, 0.4, 0.9) in the placebo group. Compared to placebo, taranabant 2–8 mg was associated with an increased incidence of psychiatric-related adverse events (e.g., depression, 8.2% versus 2.5%, P = 0.048), gastrointestinal-related adverse events (e.g., nausea, 49.7% versus 19.0%, P < 0.001), and flushing/hot flash adverse events (10.7% versus 1.9%, P = 0.002).

Conclusions

Taranabant 2–8 mg did not improve smoking cessation and was associated with increased incidences of psychiatric-related, gastrointestinal-related, and flushing adverse events (ClinicalTrials.gov NCT00109135).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CB1:

Cannabinoid-1

PHQ-9:

Patient health questionnaire-9

ECGs:

Electrocardiograms

APT:

All patients treated

References

  • Addy C, Li S, Agrawal N, Stone J, Majumdar A, Zhong L et al (2008a) Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, for the treatment of obesity: results from a double-blind, placebo-controlled, single oral dose study in healthy volunteers. J Clin Pharmacol 48:418–427 [Epub 2008 Feb 7]

    Article  CAS  PubMed  Google Scholar 

  • Addy C, Wright H, Van Laere K, Gantz I, Erondu N, Musser BJ et al (2008b) The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab 7:68–78

    Article  CAS  PubMed  Google Scholar 

  • Akbas F, Gasteyger C, Sjödin A, Astrup A, Larsen TM (2009) A critical review of the cannabinoid receptor as a drug target for obesity management. Obes Rev 10:58–67 [Epub 2008 Aug 20]

    Article  CAS  PubMed  Google Scholar 

  • Alberg AJ (2008) Cigarette smoking: health effects and control strategies. Drugs Today (Barc) 44:895–904

    Article  Google Scholar 

  • Cahill K, Ussher M (2007) Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Cochrane Database Syst Rev (4):CD005353

  • Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A (2007) Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 370:1706–1713

    Article  CAS  PubMed  Google Scholar 

  • Eisenberg MJ, Filion KB, Yavin D, Bélisle P, Mottillo S, Joseph L et al (2008) Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials. CMAJ 179:135–144

    PubMed  Google Scholar 

  • European Medicines Agency (2006) Acomplia: scientific discussion. European Medicines Agency Web site. http://www.emea.europa.eu/humandocs/PDFs/ EPAR/acomplia/H-666-en6.pdf. Accessed 15 Oct 2009

  • Filozof C, Fernández Pinilla MC, Fernández-Cruz A (2004) Smoking cessation and weight gain. Obes Rev 5:95–103

    Article  CAS  PubMed  Google Scholar 

  • Forget B, Coen KM, Le Foll B (2009) Inhibition of fatty acid amide hydrolase reduces reinstatement of nicotine seeking but not break point for nicotine self-administration—comparison with CB(1) receptor blockade. Psychopharmacology 205:613–624

    Article  CAS  PubMed  Google Scholar 

  • Gantz I, Erondu N, Suryawanshi A, Musser B, Nayee J, Johnson-Levonas AO et al (2008) A two-year study to assess the efficacy, safety, and tolerability of taranabant in obese patients: 52 week results. J Am Coll Cardiol 51(10 Suppl A):326 (Abstract 1021–220)

    Google Scholar 

  • Hughes JR, Keely J, Naud S (2004) Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 99:29–38

    Article  PubMed  Google Scholar 

  • Izzo AA, Coutts AA (2005) Cannabinoids and the digestive tract. Handb Exp Pharmacol 168:573–598

    Article  CAS  PubMed  Google Scholar 

  • Kroenke K, Spitzer RL, Williams JB (2001) The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 16:606–613

    Article  CAS  PubMed  Google Scholar 

  • Lancaster T, Stead L, Cahill K (2008) An update on therapeutics for tobacco dependence. Expert Opin Pharmacother 9:15–22

    Article  CAS  PubMed  Google Scholar 

  • Le Foll B, Goldberg SR (2005) Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. J Pharmacol Exp Ther 312:875–883 [Epub 2004 Nov 3]

    Article  PubMed  Google Scholar 

  • Le Foll B, Forget B, Aubin HJ, Goldberg SR (2008) Blocking cannabinoid CB1 receptors for the treatment of nicotine dependence: insights from pre-clinical and clinical studies. Addict Biol 13:239–252

    Article  PubMed  Google Scholar 

  • Le Foll B, Gorelick DA, Goldberg SR (2009) The future of endocannabinoid-oriented clinical research after CB(1) antagonists. Psychopharmacology (Berl) 205:171–174 [Epub 2009 Mar 20]

    Article  Google Scholar 

  • Leite CE, Mocelin CA, Petersen GO, Leal MB, Thiesen FV (2009) Rimonabant: an antagonist drug of the endocannabinoid system for the treatment of obesity. Pharmacol Rep 61:217–224

    CAS  PubMed  Google Scholar 

  • Lin LS, Lanza TJ Jr, Jewell JP, Liu P, Shah SK, Qi H et al (2006) Discovery of N-[(1 S, 2 S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. J Med Chem 49:7584–7587

    Article  CAS  PubMed  Google Scholar 

  • Nides M (2008) Update on pharmacologic options for smoking cessation treatment. Am J Med 121(4 Suppl 1):S20–S31

    Article  CAS  PubMed  Google Scholar 

  • Rucker D, Padwal R, Li SK, Curioni C, Lau DC (2007) Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 335:1194–1199

    Article  CAS  PubMed  Google Scholar 

  • Shiffman S, Elash CA, Paton SM, Gwaltney CJ, Paty JA, Clark DB, Liu KS, Di Marino ME (2000) Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving. Addiction 95(8):1185–1195

    Article  CAS  PubMed  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. Psychoparmacology 166:343–350

    CAS  Google Scholar 

  • Spitzer RL, Kroenke K, Williams JB (1999) Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary care evaluation of mental disorders. Patient health questionnaire. JAMA 282:1737–1744

    Article  CAS  PubMed  Google Scholar 

  • Ständer S, Schmelz M, Metze D, Luger T, Rukwied R (2005) Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci 38:177–188

    Article  PubMed  Google Scholar 

  • Tanda G, Goldberg SR (2003) Cannabinoids: reward, dependence, and underlying neurochemical mechanisms—a review of recent preclinical data. Psychopharmacology (Berl) 169:115–134 [Epub 2003 Jun 24]

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The following investigators participated in the study: CF Barish, Wake Research Associates, Raleigh, NC, USA; RJ Bielski, Summit Research Network, Okemos, MI, USA; CC Coleman, Mississippi Neuropsychiatric Clinic, Ridgeland, MS, USA; JM Ferguson, Radiant Research, Salt Lake City, UT, USA; LI Gilderman, University Clinical Research Associates, Inc., Pembroke Pines, FL, USA; JF Heiser, Pharmacology Research Institute, Los Alamitos, CA, USA; MB Jacobs, Radiant Research, Las Vegas, NV, USA; LR Lawson, Lovelace Scientific Resources, Inc., Albuquerque, NM, USA; PD Londborg, Summit Research Network, Seattle, WA, USA; LP Moldauer, Radiant Research, Denver, CO, USA; and MU Weerasinghe, Rochester Clinical Research, Inc., Rochester, NY, USA. The trial complied with the current laws of the country in which it was performed.

Funding support

This study was funded by Merck Research Laboratories. The funding organization was involved in the following: design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript.

Disclosure

All authors are responsible for the work described in this paper. All authors were involved in at least one of the following: conception, design, acquisition, analysis, statistical analysis, interpretation of data, and drafting the manuscript and/or revising the manuscript for important intellectual content. All authors provided final approval of the version to be published. MF Morrison is a former employee of Merck, Astra Zeneca, and Shire and, in the past 2 years, has performed consultations for the following companies (no consultations were related to smoking cessation or CB1 receptor inverse agonists): Impax, BioAdvance, FemmePharma and Orexo. P Ceesay, I Gantz, KD Kaufman, and CR Lines are employees of Merck and own stock or stock options in Merck.

Author information

Authors and Affiliations

  1. Merck Research Laboratories, Upper Gwynedd, PA, USA

    Mary F. Morrison, Paulette Ceesay & Christopher R. Lines

  2. Temple University, Philadelphia, PA, USA

    Mary F. Morrison

  3. Merck Research Laboratories, Rahway, NJ, USA

    Ira Gantz & Keith D. Kaufman

  4. Merck Research Laboratories, UG 3C-98, P.O. Box 1000, North Wales, PA, 19454-1099, USA

    Christopher R. Lines

Authors
  1. Mary F. Morrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paulette Ceesay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ira Gantz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keith D. Kaufman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher R. Lines
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher R. Lines.

Additional information

The taranabant development program for the treatment of obesity was discontinued by Merck & Co., Inc. after the completion of this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morrison, M.F., Ceesay, P., Gantz, I. et al. Randomized, controlled, double-blind trial of taranabant for smoking cessation. Psychopharmacology 209, 245–253 (2010). https://doi.org/10.1007/s00213-010-1790-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-010-1790-2

Keywords

Search

Navigation