| Effect of delta9-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans. | |
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MedLine Citation:
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PMID: 19068079 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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H Beaumont; J Jensen; A Carlsson; M Ruth; A Lehmann; Ge Boeckxstaens |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2008-12-06 |
Journal Detail:
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Title: British journal of pharmacology Volume: 156 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-12 Completed Date: 2009-05-18 Revised Date: 2010-09-22 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 153-62 Citation Subset: IM |
Affiliation:
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Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals 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 Receptors, Cannabinoid / agonists* Species Specificity Tetrahydrocannabinol / adverse effects, pharmacology* Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 0/Receptors, Cannabinoid; 158681-13-1/rimonabant; 1972-08-3/Tetrahydrocannabinol |
| Comments/Corrections | |
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