Effect of Δ⁹‐tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans

Abstract

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 CB1/CB2 receptor agonist D -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 D 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: D 9-THC significantly inhibited the increase in meal-induced TLESRs and reduced spontaneous swallowing in both dogs and humans. In humans, D 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.

Review article: the clinical relevance of transient lower oesophageal sphincter relaxations in gastro-oesophageal reflux disease

“…The effect of CBR1 agonists on the rate of TLOSRs has been studied in animal models 63,118,119 and humans. 119 It was found that CBR1 agonists reduce the rate of TLOSRs.…”

Endogenous Cannabinoid System and Its Role in Gastrointestinal Tract: Review

“…[30][31][32][33] Bu sonuçlarla doğrultulu olarak sağlıklı gönüllülerde yapılan çalışmada, ∆ 9 -THC'nin geçici LES relaksasyon sayısını azalttığı ve asit reflü ataklarında anlamlı olmayan bir azalma sağladığı gösterilmiştir. 32 Hepsi birden değerlendi-rildiğinde, CB reseptör aktivasyonunu sağlayan ilaç-ların gastroözofageal reflü tedavisinde umut verici bir yeri olduğu düşünülmektedir.…”

Reflux inhibitors – new therapy of gastroesophageal reflux disease

“…Ostatnio stwierdzono, że mieszany agonista receptorów CB1/CB2 redukuje występo-wanie indukowanych posiłkiem TLESR u zdrowych osób, ale podobnie jak baklofen wywiera działania ośrodkowe. Badanie zostało przerwane z powodu złej tolerancji: nudności, wymiotów, hipotensji, tachykardii i ośrodkowych objawów ubocznych [28].…”