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Study of the Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor and Sensory Functions in Patients With Irritable Bowel Syndrome

Phase 2
18 Years
75 Years
Not Enrolling
Irritable Bowel Syndrome

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Trial Information

Study of the Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor and Sensory Functions in Patients With Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. Despite increasing
understanding of the pathophysiology of IBS, there are unmet clinical needs and 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 type 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. The aims of
the study are to compare the effects of two doses of the cannabinoid agonist, dronabinol (5
and 10 mg/day) and placebo on gastrointestinal and colonic motor and sensory functions in
IBS. Also, to determine whether variations in the fatty acid amide hydrolase (FAAH) gene and
the monoacylglycerol lipase (MGLL) gene (for the rate limiting enzyme, monoacylglycerol
lipase, for another endocannabinoid, 2-arachidonyl glycerol) influence the pharmacological
effect of cannabinoid modulation on gastrointestinal motor and sensory functions.

All participants underwent the following procedures:

1. Documentation of eligibility, screening questionnaires, and physical examination within
the month prior to the study. The physical exam included standard rectal and pelvic
floor examinations to exclude rectal evacuation disorder. This was necessary to ensure
the diarrhea ws not secondary to "retention of stool with overflow."

2. Baseline colonic transit measurement (Geometric Center 24-h and 48-h), off treatment.

3. Treatment days corresponded to the scintigraphic transit testing days (days 1 and 2)
with participants receiving the medication to which they were randomized.
Scintigraphic measurements of gastric, small bowel, and colonic transit were conducted,
using a previously validated method on days 1 and 2, and were completed with a fasting
48-h scan on day 3 when no medication was administered.

On days 1 and 2, the morning dose of medication was ingested in the research
laboratory, with the participant fasting. On day 1, the morning dose of medication was
administered together with the delayed release capsule containing an isotope labeled
activated charcoal used to measure colonic transit. On day 2, the morning dose of
medication was given after the 24-h scan. The evening doses on days 1 and 2 were
ingested by participants at bed time in their homes.

4. With appropriate consent, a venous blood sample was to be obtained from all
participants for DNA extraction and pharmacogenomic studies.

Inclusion Criteria:

- Age 18-75 years

- Positive for IBS symptoms by Rome III criteria

- No prior abdominal surgery (except appendectomy or cholecystectomy)

- Baseline Geometric Center at 24 hours is greater/equal to 2.0

- Baseline Geometric Center at 48 hours is greater/equal to 3.9

Exclusion Criteria:

- Patients with significant depression (score of greater than 10 on Hospital and
Anxiety Inventory)

- Patients with anxiety (score of greater than 10 on Hospital and Anxiety Inventory)
will not be allowed to participate. However, patients on stable doses of selective
serotonin re-uptake inhibitors (SSRIs) or low dose of tricyclic antidepressants will
be eligible.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Outcome Measure:

Colonic Transit Geometric Center at 24 Hours

Outcome Description:

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

Outcome Time Frame:

24 hours

Safety Issue:


Principal Investigator

Michael Camilleri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Institutional Review Board

Study ID:

08-008314 Part A



Start Date:

September 2009

Completion Date:

December 2011

Related Keywords:

  • Irritable Bowel Syndrome
  • anandamide
  • cannabinoid
  • fatty acid amide hydrolase
  • gastric
  • motility
  • small bowel
  • Irritable Bowel Syndrome



Mayo Clinic Rochester, Minnesota  55905