Document Detail


Effect of delta9-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans.
MedLine Citation:
PMID:  19068079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB(1)/CB(2) receptor agonist delta(9)-tetrahydrocannabinol (delta(9)-THC) on TLESRs in dogs. Based on these findings, the effect of delta(9)-THC was studied in healthy volunteers.
EXPERIMENTAL APPROACH: In dogs, manometry was used to evaluate the effect of delta(9)-THC in the presence and absence of the CB(1) receptor antagonist SR141716A on TLESRs induced by gastric distension. Secondly, the effect of 10 and 20 mg delta(9)-THC was studied in 18 healthy volunteers in a placebo-controlled study. Manometry was performed before and for 3 h after meal ingestion on three occasions.
KEY RESULTS: In dogs, delta(9)-THC dose-dependently inhibited TLESRs and reduced acid reflux rate. SR141716A significantly reversed the effects of delta(9)-THC on TLESRs. Similarly, in healthy volunteers, delta(9)-THC significantly reduced the number of TLESRs and caused a non-significant reduction of acid reflux episodes in the first postprandial hour. In addition, lower oesophageal sphincter pressure and swallowing were significantly reduced by delta(9)-THC. After intake of 20 mg, half of the subjects experienced nausea and vomiting leading to premature termination of the study. Other side-effects were hypotension, tachycardia and central effects.
CONCLUSIONS AND IMPLICATIONS: Delta(9)-THC significantly inhibited the increase in meal-induced TLESRs and reduced spontaneous swallowing in both dogs and humans. In humans, delta(9)-THC significantly reduced basal lower oesophageal sphincter pressure. These findings confirm previous observations in dogs and indicate that cannabinoid receptors are also involved in the triggering of TLESRs in humans.
Authors:
H Beaumont; J Jensen; A Carlsson; M Ruth; A Lehmann; Ge Boeckxstaens
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2008-12-06
Journal Detail:
Title:  British journal of pharmacology     Volume:  156     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-05-18     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  153-62     Citation Subset:  IM    
Affiliation:
Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Cannabinoid Receptor Agonists*
Deglutition / drug effects
Dogs
Dose-Response Relationship, Drug
Double-Blind Method
Esophageal Sphincter, Lower / drug effects*,  physiology
Female
Gastroesophageal Reflux / drug therapy*,  physiopathology
Humans
Hydrogen-Ion Concentration
Male
Middle Aged
Muscle Relaxation
Piperidines / pharmacology
Postprandial Period
Pyrazoles / pharmacology
Receptor, Cannabinoid, CB1 / antagonists & inhibitors
Species Specificity
Tetrahydrocannabinol / adverse effects,  pharmacology*
Young Adult
Chemical
Reg. No./Substance:
0/Cannabinoid Receptor Agonists; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 158681-13-1/rimonabant; 1972-08-3/Tetrahydrocannabinol
Comments/Corrections

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


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