The cannabinoid receptor agonist delta‐9‐tetrahydrocannabinol does not affect visceral sensitivity to rectal distension in healthy volunteers and IBS patients

• Published in: Neurogastroenterology and motility Vol. 23; no. 1; pp. 30 - e2
• Main Authors: Klooker, T. K., Leliefeld, K. E. M., Van Den Wijngaard, R. M., Boeckxstaens, G. E. E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2011
• Subjects: Adult; Analgesics, Non-Narcotic - pharmacology; Analgesics, Non-Narcotic - therapeutic use; barostat; cannabinoid; Cannabinoid Receptor Agonists; Cross-Over Studies; delta9‐tetrahydr‐ocannabinol; Dilatation, Pathologic - drug therapy; Dilatation, Pathologic - physiopathology; Double-Blind Method; Dronabinol - pharmacology; Dronabinol - therapeutic use; Female; Humans; Hyperalgesia - physiopathology; Indexing in process; irritable bowel syndrome; Irritable Bowel Syndrome - drug therapy; Irritable Bowel Syndrome - physiopathology; Middle Aged; Pain Threshold - drug effects; Placebos - therapeutic use; Pressure; Rectum - drug effects; Rectum - physiopathology; Viscera - drug effects; Viscera - innervation; visceral hypersensitivity; Young Adult
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/j.1365-2982.2010.01587.x

Background  Visceral hypersensitivity to distension is thought to play an important role in the pathophysiology of the irritable bowel syndrome (IBS). Cannabinoids are known to decrease somatic pain perception, but their effect on visceral sensitivity in IBS remains unclear. Therefore, we evaluated the effect of the mixed CB1/CB2 receptor agonist delta‐9‐tetrahydrocannabinol (Δ9‐THC, dronabinol) on rectal sensitivity. Methods  Ten IBS patients and 12 healthy volunteers (HV) underwent a barostat study to assess rectal sensitivity using an intermittent pressure‐controlled distension protocol before and after sigmoid stimulation. Repetitive sigmoid stimulation is a validated method to increase visceral perception in IBS patients, consisting of a 10‐min period of 30 s stimuli (60 mmHg), separated by 30 s of rest (5 mmHg). The effect of placebo and Δ9‐THC (5 and 10 mg in healthy volunteers and 10 mg in IBS patients) on rectal sensitivity was evaluated on respectively three and two separate days in a double blind, randomized, crossover fashion. Key Results  All participants (HV and IBS) reported central side effects during the highest dose of Δ9‐THC, most frequently increased awareness of the surrounding, light‐headedness and sleepiness, whereas no side effects where reported during placebo. Although blood pressure was not affected, heart rate increased in both HV and IBS, but was most pronounced in IBS patients. The cannabinoid agonist Δ9‐THC did not alter baseline rectal perception to distension compared to placebo in HV or IBS patients. Similarly, after sigmoid stimulation there were no significant differences between placebo and Δ9‐THC in sensory thresholds of discomfort. Conclusions & Inferences  These findings imply that Δ9‐THC does not modify visceral perception to rectal distension and argue against (centrally acting) CB agonists as tool to decrease visceral hypersensitivity in IBS patients.