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Effect of Δ 9 ‐tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans
Author(s) -
Beaumont H,
Jensen J,
Carlsson A,
Ruth M,
Lehmann A,
Boeckxstaens GE
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00010.x
Subject(s) - medicine , agonist , heartburn , anesthesia , ingestion , reflux , chemistry , receptor , disease
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 Δ 9 ‐tetrahydrocannabinol (Δ 9 ‐THC) on TLESRs in dogs. Based on these findings, the effect of Δ 9 ‐THC was studied in healthy volunteers. Experimental approach: In dogs, manometry was used to evaluate the effect of Δ 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 Δ 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, Δ 9 ‐THC dose‐dependently inhibited TLESRs and reduced acid reflux rate. SR141716A significantly reversed the effects of Δ 9 ‐THC on TLESRs. Similarly, in healthy volunteers, Δ 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 Δ 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: Δ 9 ‐THC significantly inhibited the increase in meal‐induced TLESRs and reduced spontaneous swallowing in both dogs and humans. In humans, Δ 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.