Cannabis for Inflammatory Bowel Disease

A Double Blind Placebo Controlled Study of Cannabis Smoking in Inflammatory Bowel Disease

Background: The marijuana plant Cannabis has been used for centuries in the medicinal treatment of many disorders and is still the subject of medical research and public debate. Cannabinoids have been purported to alleviate a variety of neurological conditions such as MS-related symptoms including spasticity, pain, tremor and bladder dysfunction. Other neurological conditions like chronic intractable pain, dystonic movement disorders and Tourette's Syndrome were all reported to be alleviated by cannabis use. Cannabis has been used to treat anorexia in AIDS and cancer patients. In gastroenterology cannabis has been used to treat symptoms and diseases including anorexia, emesis, abdominal pain, gastroenteritis, diarrhoea, intestinal inflammation and diabetic gastroparesis.

Cannabinoids have also a profound anti inflammatory effect, mainly through the CB2 receptor. Cell mediated immunity may be impaired in chronic marijuana users. And a potent anti-inflammatory effect of cannabis was observed in rats . Studying the functional roles of the endocannabinoid system in immune modulation reveals that there are no major immune events which do not involve the endocannabinoid system. Cannabinoids shift the balance of pro-inflammatory cytokines and anti-inflammatory cytokines towards the T-helper cell type 2 profiles (Th2 phenotype), and suppress cell-mediated immunity whereas humoral immunity may be enhanced. They are therefore used for various inflammatory conditions including rheumatoid arthritis and asthma. In a mouse model of colitis cannabinoids were found to ameliorate inflammation and there are many anecdotal reports about the effect of cannabis in inflammatory bowel disease. However, there are no methodical reports of the effect of cannabis on inflammatory bowel disease. The aim of the proposed study is to examine in a double blind placebo controlled fashion the effect of smoking cannabis on disease activity in patients with IBD.

Study Overview

• Status: Unknown
• Conditions: Crohn's Disease; Ulcerative Colitis
• Intervention / Treatment: Drug: smoking of cannabis; Drug: smoking cigarettes with placebo

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Kefar Saba, Israel, 44281
    • Recruiting
    • Meir Hospital
    • Contact: Fred Konikoff, professor; Phone Number: 2525 972-9-7472580; Email: fred.konikoff@clalit.org.il
    • Contact: Timna Naftali, MD; Phone Number: 1054 972-9-7472580; Email: timna.naftali@clalit.org.il
  • Kfar Saba, Israel
    • Recruiting
    • Meir Medical Center
    • Contact: Timna Naftali, MD; Phone Number: +97297471054; Email: timna.naftali@clalit.org.il
    • Contact: Orly Mor; Phone Number: +97297471017; Email: orly.mor@clalit.org.il
    • Principal Investigator: Timna Naftali, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with a diagnosis IBD at least 3 months before recruitment will be eligible to the study.
2. Patients with active disease who are resistant to either 5 ASA, steroids or immunomodulators, or who can not receive those drugs due to adverse reactions will be offered the possibility of smoking cannabis at a dose of two cigarettes a day which will contain either regular cannabis or pre treated cannabis as placebo.
3. Disease activity index of either CDAI of more then 200 in Crohn's disease or Mayo score above 3 in UC.
4. Age above 20.

Exclusion Criteria:

1. Patients with a known mental disorder
2. Patients who are deemed to be at a high risk of abuse or addiction to the study drug.
3. Pregnant women
4. Patients who are sensitive to any of the ingredients of the study medication.
5. Patients who are unable to give informed consent.
6. Patients who may need surgery in the near future.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cannabis smoking for IBD; patients with active disease receiving active cannabis for smoking	Drug: smoking of cannabis; smoking of cannabis, 2 cigarettes a day, equivalent to about 50 mg THC
Placebo Comparator: patients smoking non active cannabis; patients with active disease receiving cannabis from which active ingredients have been chemically removed	Drug: smoking cigarettes with placebo; smoking cigarettes with cannabis that was chemically treated so that most active ingredients were removed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
reduction of CDAI by 70 points	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
adverse events due to cannabis smoking	8 weeks
change in quality of life before and at the end of study	8 weeks
change in IL-10. IL-2. TGF beta	week 0 and week 8

Collaborators and Investigators

• Sponsor: Meir Medical Center
• Investigators: Study Chair: Fred Konikoff, professor, Sackler School of Medicine Tel Aviv University; Principal Investigator: Timna Naftali, Meir Medical Center

Publications and helpful links

General Publications

• Naftali T, Bar-Lev Schleider L, Scklerovsky Benjaminov F, Konikoff FM, Matalon ST, Ringel Y. Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial. PLoS One. 2021 Feb 11;16(2):e0246871. doi: 10.1371/journal.pone.0246871. eCollection 2021.
• Naftali T, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM. Cannabis induces a clinical response in patients with Crohn's disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013 Oct;11(10):1276-1280.e1. doi: 10.1016/j.cgh.2013.04.034. Epub 2013 May 4.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): July 1, 2012

Study Registration Dates

• First Submitted: December 29, 2009
• First Submitted That Met QC Criteria: December 29, 2009
• First Posted (Estimate): December 30, 2009

Study Record Updates

• Last Update Posted (Estimate): December 16, 2011
• Last Update Submitted That Met QC Criteria: December 15, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: cannabis; IBD; Crohn's disease; Ulcerative colitis
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Digestive System Diseases; Pathologic Processes; Substance-Related Disorders; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Ulcer; Inflammatory Bowel Diseases; Crohn Disease; Marijuana Abuse; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: cannabis1