Modulatory Effects of Active Drugs on the Endocannabinoid System on Spontaneous and Induced Contractility of the Colon

The present research is aimed at defining the roles of the different components of the endocannabinoid system in the regulation of the basal contractile activity and of the excitatory motor responses induced by neuronal activation in the human colon.

Therefore, the motor effects of drugs acting on the various components of this system will be evaluated, ie receptors, biosynthetic and catabolic enzymes and membrane transporters, in colonic preparations, in conditions of basal muscle tone and on muscle contractions induced by neuronal activation.

If the modulation of one or more components of the endocannabinoid system proves to be important in the regulation of colonic contractility and probably useful for therapeutic purposes, drugs active on them could represent new treatments for constipation, diarrhea or some forms of irritable bowel syndrome, very common in the gastrointestinal tract.

Particular interest will be focused on the effects of allosteric modulators of CB1 receptors, inhibitors of biosynthetic and catabolic enzymes of endocannabinoids and inhibitors of membrane transporters of endocannabinoids.

This is an exploratory study, in which pre-specified hypotheses on pre-specified sample sizes will not be tested. Therefore, the data will be subjected only to descriptive statistics, without conducting any tests of statistical significance on them. Consequently, no primary or secondary endpoints are foreseen.

Inclusion criteria

• patients with colorectal cancer at any stage of the disease, undergoing upfront surgery or neo-adjuvant therapy for more than 6 weeks, to undergo surgery with resective intent at the UOC of General Surgery 1 of the Fondazione Policlinico Universitario A. Gemelli of Rome in the two years following the approval of the study by the Ethics Committee;

Exclusion criteria

• patients with diverticular stenosis, patients with stenosing colorectal cancer (defined as a tumor that cannot be passed through endoscopically, resulting in clinical and/or radiological symptoms of intestinal obstruction), urgent/emergency procedures, patients treated with corticosteroid therapy for immuno-rheumatic diseases, patients treated with radio-chemotherapy and undergone surgery for less than 6 weeks, surgically resected patients who present macroscopic lesions near the resection margin when opening the surgical piece, refusal of informed consent.