Cannabinoid Activator Mellows Out Colon


Drugs that activate cannabinoid receptors in the colon might help treat lower GI conditions such as diarrhea or certain types of fecal incontinence, according to a proof-of-concept study presented here.

The study found that Marinol (dronabinol) significantly relaxed the colon in healthy volunteers who had consumed a 1,000-calorie chocolate milkshake, reported Tuba Esfandyari, M.D., of the Mayo Clinic in Rochester, Minn., at the American College of Gastroenterology meeting here.

The study is the first to demonstrate that the drug, a synthetic version of the natural compound delta-9-THC found in the marijuana plant, may also have beneficial effects in the lower colon, said co-author Michael Camilleri, M.D., also of the Mayo Clinic. Marinol is approved to treat nausea, vomiting, and lack of appetite during chemotherapy.

In the double-blind, parallel-group study, 52 volunteers were randomly assigned to a single dose of 7.5 mg of Marinol or placebo. Thirty of the volunteers were women and 22 were men. Their average age was about 35.

Before taking Marinol, baseline measurements of colonic contraction and sensation were taken. These measurements were repeated one hour after taking the medication. Finally, the measurements were taken once again an hour after participants drank the milkshake.

Compared with placebo, the drug was associated with significant inhibition of postprandial colonic contractions (P=0.048) as well as a non-significant effect on fasting colonic contractions (P=0.096), the researchers reported.

The effect on colonic contraction was more pronounced in women than men, the researchers said, although data on the gender difference was not reported.

The drug also had an overall significant relaxing effect on the colon (P=0.045), the study found.

The drug did not appear to have a significant effect on participants’ feelings of abdominal pain or discomfort after ingesting the milkshake, the study authors reported.

Nevertheless, the results suggest that “the potential for cannabinoids to modulate colonic motor function in disease deserves further study,” the investigators concluded.

More specifically, the drug’s ability to inhibit colonic contraction after a meal might help treat certain types of fecal incontinence that are not based on abnormal sphincter function but on unusually strong colonic contractions, Dr. Camilleri said.

The drug, or others like it, might also be useful for treating the diarrhea associated with irritable bowel syndrome, he said.

Marinol is a non-selective cannabinoid activator, but the study suggests selective cannabinoid activators might have the same effects on the colon, Dr. Camilleri said.

Selective cannabinoid activators would likely not have the psychoactive side effects associated with Marinol or other non-selective cannabinoid activators. However, Marinol was the only drug available for study in humans, Dr. Camilleri said.

Marinol is made by Slovay Pharmaceuticals of Marietta, Ga. The company did not fund this study.

Primary source: American College of Gastroenterology
Source reference:
Tuba Esfandyari et al. “A non-selective cannabinoid agonist relaxes the colon and reduces post-prandial colonic contraction in humans.” Abstract number 25. Presented at the American College of Gastroenterology Annual Meeting, Las Vegas, Nevada, October 23-25, 2006.