Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, Clinical Neurology, Neurosciences, Neurosciences & Neurology, barostat, cannabinoid, delta9-tetrahydr-ocannabinol, irritable bowel syndrome, visceral hypersensitivity, IRRITABLE-BOWEL-SYNDROME, RAT MODEL, HYPERALGESIA, PERCEPTION, PAIN, Adult, Analgesics, Non-Narcotic, Cannabinoid Receptor Agonists, Cross-Over Studies, Dilatation, Pathologic, Double-Blind Method, Dronabinol, Female, Humans, Hyperalgesia, Irritable Bowel Syndrome, Middle Aged, Pain Threshold, Placebos, Pressure, Rectum, Viscera, Young Adult, 1103 Clinical Sciences, 1109 Neurosciences, 1116 Medical Physiology, 3202 Clinical sciences, 3208 Medical physiology, 3209 Neurosciences

Abstract:

Abstract 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 CB(1)/CB(2) receptor agonist delta-9-tetrahydrocannabinol (Delta(9)-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 Delta(9)-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 Delta(9)-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 Delta(9)-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 Delta(9)-THC in sensory thresholds of discomfort. Conclusions & Inferences These findings imply that Delta(9)-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.