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

Morrison, Mary F.; Ceesay, Paulette; Gantz, Ira; Kaufman, Keith D.

doi:10.1007/s00213-010-1790-2

Cited by 24 publications

(14 citation statements)

References 27 publications

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“…MK-0364 contains taranabant, a CB1R inverse agonist, which acts by reducing food intake and increasing energy expenditure and fat oxidation. In a recent large Phase II randomized clinical trial, 8-week treatment with MK0364 did not improve smoking cessation and was associated with increased incidence of psychiatric adverse events, gastrointestinal discomfort, and flushing [52]. …”

Section: Cannabinoid Receptor 1 Antagonismmentioning

confidence: 99%

Treatment of nicotine addiction: present therapeutic options and pipeline developments

Polosa

Benowitz

2011

Trends in Pharmacological Sciences

120

105

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Tobacco use is a global pandemic that poses a substantial and costly health burden. There are some treatment options are available, but currently marketed smoking-cessation drugs lack high levels of efficacy, particularly in real-life settings. Consequently, there is a compelling need for more effective pharmacotherapies to aid smokers in maintaining long-term abstinence. Advances in the understanding of the mechanisms involved in nicotine dependence have recently been translated into new medications and vaccines that interfere with nicotine signaling, many of which are currently at an advanced stage of development. In the present article we review current and emerging pharmacotherapies for tobacco dependence, focusing on the mechanistic rationale for their potential anti-addiction efficacy, major findings in preclinical and clinical studies, and future research directions.

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Section: Cannabinoid Receptor 1 Antagonismmentioning

confidence: 99%

Treatment of nicotine addiction: present therapeutic options and pipeline developments

Polosa

Benowitz

2011

Trends in Pharmacological Sciences

120

105

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“…While the significant weight loss effects can only be measured after a few weeks, Morrison et al . reported that with taranabant, the largest percentage of psychiatric adverse events occurred within the first 4 days of treatment .…”

Section: Introductionmentioning

confidence: 99%

“…The results of clinical studies on rimonabant and taranabant showed that both the desired and undesired effects were dose related, with greater efficacy and more adverse events at the highest doses [7,[17][18][19]. While the significant weight loss effects can only be measured after a few weeks, Morrison et al reported that with taranabant, the largest percentage of psychiatric adverse events occurred within the first 4 days of treatment [21].…”

Section: Introductionmentioning

confidence: 99%

Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ⁹‐tetrahydrocannabinol‐induced central nervous system and heart rate effects in humans

Klumpers

Roy

Ferron

et al. 2013

Brit J Clinical Pharma

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AIMCannabinoid receptor type 1 (CB1) antagonists have been developed for the treatment of obesity and associated risk factors. Surinabant is a high affinity CB1 antagonist in vitro. The aim of this study was to assess the magnitude of inhibition by surinabant of CNS effects and heart rate induced by D 9 -tetrahydrocannabinol (THC) in humans. METHODSThis was a double-blind, placebo-controlled, randomized, four period six sequence crossover study. Thirty healthy young male occasional cannabis users (<1 per week) were included. A single oral dose of surinabant (5, 20 or 60 mg) or placebo was administered followed 1.5 h later by four intrapulmonary THC doses (2, 4, 6 and 6 mg) or vehicle, administered at 1 h intervals. The wash-out period was 14-21 days. Subjective and objective pharmacodynamic (PD) measurements were performed. A population PK-PD model for THC and surinabant quantified PK and PD effects. RESULTSSurinabant 20 and 60 mg inhibited all THC-induced PD effects in a similar range for both doses with inhibition ratios ranging from 68.3% (95% CI = 32.5, 104.2; heart rate) to 91.1% (95% CI = 30.3, 151.8; body sway). IC50 ranged from 22.0 ng ml -1 [relative standard error (RSE) = 45.2%; body sway] to 58.8 ng ml -1 (RSE = 44.2%; internal perception). Surinabant 5 mg demonstrated no significant effects. CONCLUSIONSThe dose-related inhibition by surinabant, without any effect of its own, suggests that this compound behaves as a CB1 receptor antagonist in humans at these concentrations. A single surinabant dose between 5 to 20 mg and above was able to antagonize THC-induced effects in humans. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Rimonabant was the first cannabinoid receptor type 1 (CB1) inverse agonist that reached the market. However, with the doses used in patients, it caused severe side effects. We wanted to investigate the dose-effect profile and the effective dose range of surinabant, a new CB1 antagonist in healthy subjects. WHAT THIS STUDY ADDS• This study provides insight into the effective surinabant dose range in healthy subjects using a D 9 -tetrahydrocannabinol (THC) challenge test. Surinabant is able to inhibit various tests, such as heart rate, body sway and feeling high. In our model, surinabant is already maximally effective at single doses of 20 mg, and possibly even below.

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“…& Some have proposed that cannabinoid-1 (CB1) receptor inverse antagonists might be effective for smoking cessation, but a recent randomized trial found that taranabant did not improve smoking cessation rates and was associated with increased adverse events [43]. Rimonabant, which is also a CB1 antagonist, has a pooled odds ratio for smoking cessation of 1.6 at the 20-mg dose, with an added benefit of significantly less weight gain [44].…”

Section: Emerging Therapiesmentioning

confidence: 98%

Approach to Smoking Cessation in the Patient With Vascular Disease

Ratchford¹,

Black

2011

Curr Treat Options Cardio Med

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In the patient with vascular disease, cigarette smoking is particularly perilous; the benefits of smoking cessation greatly exceed any risks associated with pharmacologic treatment. The patient with claudication is often uniquely motivated to quit smoking because 1) there is a chance that the leg pain will improve and 2) smoking cessation may prevent disease progression and thus invasive procedures. The first step toward success is a systematic approach with focus on the 5 A's (Ask, Advise, Assess, Assist, and Arrange). Multiple clinical trials have demonstrated the efficacy of pharmacologic therapy for smoking cessation. The most effective medications available are bupropion and varenicline. If the patient is ready to quit, varenicline is typically first-line unless contraindicated. If the patient has concomitant signs or symptoms of depression, bupropion in combination with nicotine replacement therapy is preferred. In parallel with aggressive counseling and pharmacotherapy for smoking cessation, cardiovascular risk reduction is critical. Established atherosclerotic vascular disease (including peripheral artery disease, abdominal aortic aneurysm, or carotid artery disease) plus poorly controlled risk factors, including current smoking, place the patient in the "very high-risk" category, which favors reducing the low-density lipoprotein level to less than 70 mg/dL. The increased cardiovascular risk associated with smoking is tremendous, particularly in the vascular patient. Smoking cessation is critical, and no other health intervention offers such a large potential benefit.

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

Abstract: 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).

Cited by 24 publications

References 27 publications

Treatment of nicotine addiction: present therapeutic options and pipeline developments

Treatment of nicotine addiction: present therapeutic options and pipeline developments

Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ⁹‐tetrahydrocannabinol‐induced central nervous system and heart rate effects in humans

Approach to Smoking Cessation in the Patient With Vascular Disease

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

Abstract: 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).

Cited by 24 publications

References 27 publications

Treatment of nicotine addiction: present therapeutic options and pipeline developments

Treatment of nicotine addiction: present therapeutic options and pipeline developments

Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ9‐tetrahydrocannabinol‐induced central nervous system and heart rate effects in humans

Approach to Smoking Cessation in the Patient With Vascular Disease

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Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ⁹‐tetrahydrocannabinol‐induced central nervous system and heart rate effects in humans