The clinical manifestations may be quite variable, but both disorders run a chronic course of alternating exacerbations and remissions. Symptoms include abdominal pain and diarrhea, often with blood, especially when the colon is involved. Importantly, there is an increased risk of cancer of the involved organs. Both disorders may also involve extraintestinal organs, such as the skin, joints and eyes, as well as the skeletal or hepatobiliary systems .
Despite the relatively wide spectrum of therapeutic agents, the medical response remains incomplete. Corticosteroids, the most potent agents, achieve a remission rate of up to 80%, but due to significant side effects cannot be used for long-term maintenance . Most other immunomodulators as well as biological therapies provide a remission rate of 50–60% only, and there is no curative medical treatment. Furthermore, over 30% of patients, and over 70% with Crohn’s disease, will need surgical intervention for their disease .
These results prompted us to conduct the first randomized placebo-controlled trial of cannabis in Crohn’s disease . The study included 21 active Crohn’s disease patients who received cannabis cigarettes containing 23% of THC or placebo for 8 weeks. Complete remission (Crohn’s Disease Activity Index, CDAI, score < 150) was achieved by 5/11 subjects in the cannabis group (45%) and 1/10 in the placebo group (10%, P = 0.43). A clinical response (decrease in CDAI score > 100) was observed in 10/11 subjects in the cannabis group (90%, from 330 ± 105 to 152 ± 109) and 4/10 in the placebo group (40%, from 373 ± 94 to 306±143,P=0.028). However,in another randomized placebo controlled study, low dose cannabidiol alone given to 19 Crohn’s disease patients did not show a beneficial effect . The average CDAI before CBD consumption was 337 ± 108 and 308 ± 96 (P = NS) in the CBD and placebo groups, respectively. After 8 weeks of treatment the index decreased to 220 ± 122 in the CBD group and 216 ± 121 in the placebo group (P = NS). No side effects were observed . It should be noted that this study used a very small dose of 10 mg/day, whereas several studies of cannabidiol in a variety of human diseases used a dose range of 200–800 mg/day.
These human studies are, however, limited by both the small number of patients and the fact that inflammatory activity was not measured before and after cannabis. We therefore initiated two additional randomized placebo-controlled studies. The first looks into the use of cannabis oil, rich in CBD, in Crohn’s disease. Outcome measures include inflammatory markers, such as calprotectine and CRP, as well as endoscopic evaluation before and after treatment. The second study assesses the effect of cannabis smoking on ulcerative colitis, measuring inflammatory markers and endoscopic scoring, as well as clinical indices. We hope that these studies will enable us to better define the role, if any, of cannabis in the treatment of IBD.
Use of cannabis by patients naturally raises a host of safety concerns. Information about patterns of use, dosage, side effects and effects on patients’ function is limited. We therefore conducted a survey of 127 IBD patients who use cannabis regularly. Patients were asked to fill out questionnaires on their patterns of use, the dose, the effect on well-being, disease activity and side effects. We also looked at the employment status of patients before and after cannabis use. Addiction trait was assessed by the criteria defined in DSM-IV. The average age of the patients was 39.6 years, 86 were males, and 107 had Crohn’s disease with an average duration of disease of 14 years. The mean duration of cannabis use was 38 months (range 2–126 months). Most patients maintained a stable dose of cannabis throughout that period with an initial dose of 28 ± 16 g/month and a final dose of 31 ± 15 g/month. The mode of use was smoking in 72%. Half the patients (51%) were fully employed before starting cannabis and their employment status was increased to 64% while using cannabis. Side effects were minor, and included dry mouth in 62 patients (48%) and eye irritation in 13 (10%). Memory impairment was mentioned by 33 patients (25%), but it did not seem to compromise any activity .
In conclusion, use of cannabis is common in IBD, and it seems to be mostly safe. Accumulating preliminary data from human studies support a beneficial role of cannabinoids in IBD. Whether the effect is anti-inflammatory, central or other remains speculative at this stage. Despite active interest within the gastroenterology community following our initial randomized controlled trial (RCT) of cannabis in CD, it still remains the sole RCT published. Thus, additional controlled trials in larger patient populations are clearly needed. These should focus on optimizing delivery mode and dosage, as well as evaluating clinical efficacy. Data should be correlated with experimental laboratory data. Hopefully, these will lead to the identification of the effective cannabinoid(s) for clinical use. Last, but not least, careful monitoring of the effects and side effects in patients within studies as well as out of studies remains crucial.
F.K. was supported in part by the Josefina Maus and Gabriela Cesarman Chair for Research in Liver Diseases, Sackler Faculty of Medicine, Tel Aviv University
dr. t. naftali
Institute of Gastroenterology and Hepatology, Meir Hospital, Kfar Saba 44281, Israel
Phone: (972-9) 747-2473
Fax: (972-9) 747-2725
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