Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study.
Cannabinoid receptors (CBR) are located on cholinergic neurons in the brain stem, stomach, and colon. CBR stimulation inhibits motility in rodents. Effects in humans are unclear. Dronabinol (DRO), a nonselective CBR agonist, inhibits colonic motility and sensation. The aim of this study was to compare effects of DRO and placebo (PLA) on colonic motility and sensation in healthy volunteers. Fifty-two volunteers were randomly assigned (double-blind) to a single dose of 7.5 mg DRO or PLA postoperative with concealed allocation. A balloon-manometric assembly placed into the descending colon allowed assessment of colonic compliance, motility, tone, and sensation before and 1 h after oral ingestion of medication, and during fasting, and for 1 h after 1,000-kcal meal. There was an overall significant increase in colonic compliance (P = 0.045), a borderline effect of relaxation in fasting colonic tone (P = 0.096), inhibition of postprandial colonic tone (P = 0.048), and inhibition of fasting and postprandial phasic pressure (P = 0.008 and 0.030, respectively). While DRO did not significantly alter thresholds for first gas or pain sensation, there was an increase in sensory rating for pain during random phasic distensions at all pressures tested and in both genders (P = 0.024). In conclusion, in humans the nonselective CBR agonist, DRO, relaxes the colon and reduces postprandial colonic motility and tone. Increase in sensation ratings to distension in the presence of relaxation of the colon suggests central modulation of perception. The potential for CBR to modulate colonic motor function in diarrheal disease such as irritable bowel syndrome deserves further study.
Esfandyari
Tuba
T
Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.
Camilleri
Michael
M
Busciglio
Irene
I
Burton
Duane
D
Baxter
Kari
K
Zinsmeister
Alan R
AR
D000328:Adult; D063386:Cannabinoid Receptor Agonists; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D003187:Compliance / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology*; D005215:Fasting; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D010146:Pain; D012684:Sensory Thresholds / Q000187:drug effects
D063386:Cannabinoid Receptor Agonists; D013759:Dronabinol