Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebo‐controlled study

Abstract

Cannabinoid receptor (CBR) stimulation inhibits motility and increases food intake in rodents. Effects of CBR stimulation in human gastrointestinal (GI) tract are unclear. We compared effects of dronabinol (DRO) and placebo (PLA) on GI transit, gastric volume and satiation in humans. In a double-blind, randomized study, 30 healthy volunteers were randomly assigned to DRO 5 mg b.i.d. or PLA for three doses. We measured GI functions noninvasively: day 0, Ensure satiation test to measure maximum tolerated volume (MTV) and 30-min post-Ensure symptoms; day 1, scintigraphic transit ((111)In-egg meal) and fasting and postprandial gastric volume ((99Tcm)-SPECT); day 2, 24-h colonic transit and repeat satiation test. ancova was used to compare treatment groups with gender, age, and, for the satiation test, the baseline MTV, as covariates. A log-rank test was used to assess treatment effects on gastric emptying. Planned sample size had 80% power to detect 25-30% differences in primary end points. There was an overall retardation of gastric emptying with DRO (P = 0.018); this was more pronounced in females (P = 0.011), than in males (P = 0.184). No significant treatment differences were detected for gastric volumes, MTV, post-Ensure(R) symptoms, small bowel and colonic transit. Fasting gastric volume was greater in males receiving DRO compared with PLA (238 +/- 17 vs 185 +/- 16, P = 0.04). DRO retards gastric emptying in humans; effects are gender-related. Dronabinol also increases fasting gastric volumes in males.

Sex Differences in Cannabinoid 1 vs. Cannabinoid 2 Receptor-Selective Antagonism of Antinociception Produced by Δ9-Tetrahydrocannabinol and CP55,940 in the Rat

“…Sex differences in cannabinoid effects also have been demonstrated in humans. For example, dronabinol (synthetic THC) retarded gastric emptying to a greater extent in women than men (Esfandyari et al, 2006), and women reported more dizziness than men after cannabinoid intake (Mathew et al, 2003). In contrast, men reported greater ratings of "high" as well as some other subjective effects after cannabinoid intake (Haney, 2007).…”

Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits

“…The study was based on previously identified patients with functional gastrointestinal disorders (n ϭ 455) and healthy controls (n ϭ 228), all of whom reside in the Midwest USA. Cannabinoid receptors, especially CNR1, are reported to affect numerous gastrointestinal functions, including pain modulation, inflammation, and gastric and colonic motility (11,12,15).…”

“…Esfandyari et al (11,12) have shown that a nonselective CB receptor agonist, dronabinol, inhibits gastric emptying and colonic motility in humans.…”

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

“…Cannabinoid receptors modulate a variety of GI functions, including pain modu-lation, inflammation, and gastric and colonic motility (55), in healthy humans (34,35). A recent study has further demonstrated that use of a cannabinoid agonist may reduce fasting colonic motility in patients with nonconstipated IBS and in patients with IBS (116) and, therefore, represents a therapeutic target.…”