, Volume 209, Issue 3, pp 245–253 | Cite as

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

  • Mary F. Morrison
  • Paulette Ceesay
  • Ira Gantz
  • Keith D. Kaufman
  • Christopher R. LinesEmail author
Original Investigation



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.


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.


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).


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


Taranabant Cannabinoid-1 receptor inverse agonist Smoking cessation Randomized clinical trial 





Patient health questionnaire-9




All patients treated



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.


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.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Mary F. Morrison
    • 1
    • 2
  • Paulette Ceesay
    • 1
  • Ira Gantz
    • 3
  • Keith D. Kaufman
    • 3
  • Christopher R. Lines
    • 1
    • 4
    Email author
  1. 1.Merck Research LaboratoriesUpper GwyneddUSA
  2. 2.Temple UniversityPhiladelphiaUSA
  3. 3.Merck Research LaboratoriesRahwayUSA
  4. 4.Merck Research LaboratoriesNorth WalesUSA

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