Document Detail

Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans.
MedLine Citation:
PMID:  23278647     Owner:  NLM     Status:  MEDLINE    
AIM: Cannabinoid 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 Δ(9) -tetrahydrocannabinol (THC) in humans.
METHODS: This 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.
RESULTS: Surinabant 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.
CONCLUSIONS: The 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.
Linda E Klumpers; Christine Roy; Geraldine Ferron; Sandrine Turpault; Franck Poitiers; Jean-Louis Pinquier; Johan G C van Hasselt; Lineke Zuurman; Frank A S Erwich; Joop M A van Gerven
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  76     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-20     Completed Date:  2014-02-03     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  65-77     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Cannabinoid Receptor Agonists / administration & dosage,  pharmacology
Cannabinoid Receptor Antagonists / administration & dosage,  pharmacology*
Central Nervous System / drug effects,  metabolism
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Dronabinol / administration & dosage,  pharmacology*
Heart Rate / drug effects*
Models, Biological
Piperidines / administration & dosage,  pharmacology*
Pyrazoles / administration & dosage,  pharmacology*
Receptor, Cannabinoid, CB1 / antagonists & inhibitors
Young Adult
Reg. No./Substance:
0/Cannabinoid Receptor Agonists; 0/Cannabinoid Receptor Antagonists; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 0/surinabant; 7J8897W37S/Dronabinol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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