The Effect of CanChew® Cannabidiol (CBD) Containing Chewing Gum on Irritable Bowel Syndrome

Rationale: IBS is the most common functional gastrointestinal disorder with a prevalence worldwide ranging from 9-23%. Complaints include abdominal discomfort or pain and altered bowel habits. Although the condition is not life-threatening, it strongly impairs quality of life and up to now there is no cure for IBS. It is assumed that IBS symptoms are related to a combination of altered gut motility and secretion, and visceral hypersensitivity. However, its primary cause still remains largely unknown. The endocannabinoid system, together with some functionally related receptors is among the biological targets considered promising for treatment. Modulation of the CB1 , CB2 and related receptors or enzymes of the endocannabinoid system in a broader sense by (endo) cannabinoids or (and) structurally related lipid mediators can influence motility, secretions and decrease hypersensitivity in the gut. Among the plant-derived cannabinoids or so called 'phytocannabinoids', cannabidiol (CBD) is of special interest as it has shown therapeutic potential in preclinical studies and a growing number of case-reports. CBD is a non-specific phytocannabinoid displaying a broad but weak receptor interaction profile. In contrast to the well-known THC from Cannabis sativa, CBD is not psychoactive and often also present in those Cannabis varieties that are not used for their psychoactive properties but for industrial (fibre) or food properties (oil, flour and seeds) instead. Based on preclinical studies and in vitro data we hypothesize that CBD might be able to relieve symptoms of IBS, including pain in patients with IBS. The chewing gum is to be taken 'on demand' and may have some additional perceived positive effects.

Objective: To investigate whether the use of a CBD-containing preparation in the form of CanChew® chewing gum can contribute to a reduction of IBS symptoms and an improvement of perceived wellbeing in patients with IBS.

Study design: A randomized, double-blind, cross-over trial of 8 weeks in total.

Study population: Adults, aged 18-65, diagnosed according to the ROME III criteria with Irritable Bowel Syndrome.

Intervention (if applicable): Patients will, in this cross-over study, receive a maximum 6 chewing gums per day, either containing 50 mg of cannabidiol per chewing gum in case of the CanChew chewing gum, or a placebo chewing gum. This first intervention period will last 3 weeks. Next, participants will undergo a one week wash-out and then switch intervention to either placebo or the CanChew chewing gum for another 3 weeks.

Main study parameters/endpoints: The main study parameter is a change in pain reduction perception experienced and measured by the patient using VAS-scales before and after taking the chewing gum, to be recorded in a diary. Next to this a patient is asked to provide one VAS score for each completed week. Furthermore, the adequate relief will be measured every day. At the end of each week patients will also be asked (from their diary) whether they noticed a change in stool frequency or (and) experienced any side-effects. For the disease-related quality of life the IBS-QOL will be used. This questionnaire will be filled out in week 1, 4, 5, and 8.