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    
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.
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    
Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands.
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MeSH Terms
Cannabinoid Receptor Agonists*
Deglutition / drug effects
Dose-Response Relationship, Drug
Double-Blind Method
Esophageal Sphincter, Lower / drug effects*,  physiology
Gastroesophageal Reflux / drug therapy*,  physiopathology
Hydrogen-Ion Concentration
Middle Aged
Muscle Relaxation
Piperidines / pharmacology
Postprandial Period
Pyrazoles / pharmacology
Receptor, Cannabinoid, CB1 / antagonists & inhibitors
Species Specificity
Tetrahydrocannabinol / adverse effects,  pharmacology*
Young Adult
Reg. No./Substance:
0/Cannabinoid Receptor Agonists; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 158681-13-1/rimonabant; 1972-08-3/Tetrahydrocannabinol

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