Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study

Abstract

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.

CB1Receptors Mediate the Analgesic Effects of Cannabinoids on Colorectal Distension-Induced Visceral Pain in Rodents

“…Nevertheless, there is not a clear correlation between compliance and pain perception (Käll et al, 2007;Lindström et al, 2008;Ravnefjord et al, 2008). Experimental data in humans showed that the nonselective cannabinoid dronabinol reduced colonic tone and increased compliance while increasing sensation ratings to distension, probably through the central modulation of perception (Esfandyari et al, 2007). In the present experiments, WIN55,212-2, at analgesic doses, did not modify the pressure-volume relationship during distension indicating a lack of effect modulating colonic compliance.…”

“…Recent studies in several species, including humans, support a role for endocannabinoids modulating visceral pain (Jaggar et al, 1998;Farquhar-Smith et al, 2002;Sanson et al, 2006;Esfandyari et (2006) implicated CB 1/2 Rs in the modulation of basal viscerosensitivity in rats. However, according to the present results, CB 1 Rs account for the full analgesic effects of cannabinoids on basal CRD-associated pain responses.…”

“…According to these studies, both CB 1 Rs and CB 2 Rs elicited analgesic responses under basal conditions (Sanson et al, 2006) and during states of inflammation-induced hyperalgesia (Sanson et al, 2006;Kikuchi et al, 2008). Interestingly, the only data available in humans showed that the CB 1 /CB 2 nonselective agonist, dronabinol, relaxed the colon but increased sensation ratings to distension in healthy volunteers (Esfandyari et al, 2007). This was interpreted as an interaction between the colonic motor effects and the central action of cannabinoids modulating perception (increasing awareness).…”

Endogenous Cannabinoid System and Its Role in Gastrointestinal Tract: Review

“…45,46 VİSERAL DUYARLILIK CB'lerin viseral ağrı üzerine etkili olduğu birçok hayvan çalışmasında gösterilmiştir. CB1 ve CB2 reseptör agonistlerinin hem kolorektal distansiyon ile oluştu-rulmuş ağrı modelinde hem de inflamatuar uyaran ile oluşturulmuş viseral ağrı modelinde etkili olduğu gös-terilmiştir.…”

“…46 Ancak bu hasta grubunda uyuşukluk, baş dönmesi ve sersemlik gibi yan etkilerin olması nedeni ile daha düşük dozlarda (2,5 ve 5 mg) ilacın kullanıl-dığı bir çalışmada, hastalarda tedavide fayda göz-lenmemiştir. 55 CB'lerin güçlü antiinflamatuar ve immünmo-dülator etkileri olması nedeni ile inflamatuar ve ağrı ile seyreden inflamatuar barsak hastalıkları (İBH)'nda etkin olabileceği düşünülmüştür.…”