From animal studies it was rightfully concluded that cannabinoid agonists could improve visceral pain thresholds in humans. In a previous study performed in healthy volunteers to investigate the effect of dronabinol (Δ9-THC) on colonic motility and sensation, 7.5 mg dronabinol induced relaxation of colon motility and tone postprandially (72). The effect of dronabinol on visceral perception to rectal distension was then tested in IBS patients (positively diagnosed by Rome II criteria) and healthy subjects in a small trial, but no differences in sensory thresholds and discomfort were observed between the cohorts (73). A different study revealed inhibitory effects of dronabinol on fasting colonic motility and an increase in colonic compliance, particularly in patients with diarrhea predominant forms of IBS, but failed to demonstrate effects on sensation and tone (74). The report also suggested that FAAH and CNR1 variants could have had an impact on the effects of dronabinol (74). In a subsequent trial performed in IBS-D patients, no significant effect of dronabinol on colonic transit was observed; however, in a subset of patients with the CNR1 polymorphism rs806378, dronabinol moderately delayed colonic motility (75).
Thus, it seems that CB receptor activation in IBS has potential therapeutic value, but probably only in IBS-D patients with genetic variations of ECS components.