Effect of a Cannabinoid Agonist on Colonic Sensory Functions in Patients With Irritable Bowel Syndrome
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. There are still no
      effective and safe medications approved for the treatment of abdominal pain associated with
      bowel symptoms in IBS. This study will investigate the effects of an approved medication,
      Dronabinol, on the movement of food through the stomach and colon in subjects with a history
      of diarrhea-predominant Irritable Bowel Syndrome (D-IBS).
    

Detailed description: 
      Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. Despite increasing
      understanding of the pathophysiology of IBS, there is no effective medication approved for
      the treatment of abdominal pain associated with IBS. Cannabinoid receptors (CBR) are on
      cholinergic neurons in the brain stem, stomach and colon. A cannabinoid receptor 1 (CB1)
      antagonist, rimonabant, is effective in induction of weight loss; however, the mechanism of
      this benefit is unclear. Human studies from this lab show that a CBR agonist, dronabinol,
      inhibits gastric and colonic motility, which may alter appetite or satiation in obesity, and
      may have potential in the treatment of IBS. The overall focus of the study is on the
      mechanisms involved in the modulation of gastric and colonic motor and sensory functions by
      cannabinoid receptors (CBR) in health and in IBS. CB1 receptors are also involved in
      nociception and in mediating inflammation which are increasingly recognized as being
      potential pathophysiological mechanisms in IBS.

      All participants underwent the following procedures:

        1. Documentation of eligibility, screening questionnaires and physical examination,
           including exclusion of rectal evacuation disorder by standard clinical evaluation within
           the past 12 months; this was important to ensure the diarrhea was not secondary to
           "retention with overflow".

        2. Bowel preparation with PEG and electrolyte-containing oral colonic lavage solution,
           followed by a 12 hour fast.

        3. Colonic testing of compliance, tone, motility and sensation measurement. Colonic
           compliance, fasting tone, sensory thresholds and sensory ratings in response to
           random-order phasic distensions were performed before treatment was administered. Then
           medication was ingested, and after 60 minutes, the same studies were performed that is
           compliance, fasting tone, sensory thresholds and sensory ratings in response to
           random-order phasic distensions. Participants also filled in responses to questionnaires
           (using 100 mm VAS scales) to describe their sense of tiredness, peace, worry and
           activity at the time of the measurements of sensation. Finally, participants ingested a
           standard chocolate 1000 kcal milkshake meal, and postprandial colonic tone and motility
           were measured for one hour.

        4. With appropriate consent, a venous blood sample was obtained from each participant for
           DNA extraction; this will be used in ongoing pharmacogenomics studies.

      Note: This study is related to NCT01253408, part A of the same protocol. Part A explored the
      effect of dronabinol on gastric and colonic motor functions.
    

Intervention name(s): Dronabinol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Dronabinol is a synthetic delta-9-tetrahydrocannabinol, a nonselective cannabinoid agonist. Subjects received one dose of either 2.5 mg or 5 mg orally with water.; Placebo will match study drug; taken as one dose orally with water.
Other intervention name(s): Marimol
Intervention MeSH terms: Dronabinol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Keywords: anandamide; cannabinoid; fatty acid amide hydrolase; gastric; motility; small bowel; sensory; motor