Eight weeks of therapy with Δ9-tetrahydrocannabinol (THC)-rich cannabis reduced symptoms in patients with active Crohn’s disease, according to a controlled trial published in the October issue of Clinical Gastroenterology and Hepatology. However, these effects were only temporary.
The marijuana plant Cannabis sativa has been used for centuries to treat a variety of ailments. Cannabis contains more than 60 different compounds, collectively referred to as cannabinoids. Although Δ9-tetrahydrocannabinol (THC) and cannabidiol seem to be most active, other unknown ingredients could have beneficial effects.
Cannabis has been used to treat a number of GI disorders, including diarrhea and diabetic gastroparesis. Cannabinoids were shown to reduce inflammation in mice with colitis, and the combination of THC and cannabidiol is more effective than either substance alone.
Cannabis has also been reported to have beneficial effects in patients with inﬂammatory bowel diseases, but this has not been proven in controlled trials. Timna Naftali et al. conducted the first double-blind, placebo-controlled study to investigate the effects of cannabis on patients with active Crohn’s disease.
Twenty-one patients with Crohn’s disease activity scores between 200 and 450 points, who had not responded to previous treatments, were randomly assigned to groups given either medical cannabis or placebo, in the form of cigarettes. Each test cigarette contained 0.5 g of dried cannabis flowers (flowers have a higher THC content than leaves), corresponding to 115 mg THC. Placebo cigarettes were made of cannabis flowers from which THC had been extracted.
After 8 weeks, the mean reductions in Crohn’s disease activity scores were 177 ± 80 among patients who smoked the THC-rich cannabis and 66 ± 98 in the placebo group.
A clinical response (decrease in disease activity score of >100) was observed in 90% of subjects in the THC group (3 were able to stop steroid therapy) and only 40% of the placebo group.
Considering that the participants had longstanding Crohn’s disease, with 80% nonresponsive or intolerant to anti-tumor necrosis therapy, this result is impressive. However, the observed improvements were only symptomatic—there was no evidence for reduced intestinal inflammation. In addition, patients relapsed 2 weeks after cannabis treatment was stopped.
The THC did not appear to cause any signiﬁcant side effects. The subjects did not report signiﬁcant differences in concentration, memory, or confusion. None of them had difficulty stopping THC therapy after 8 weeks or withdrawal symptoms.
How might THC reduce the symptoms of inflammatory bowel diseases?
Cannabinoids have strong anti-inflammatory effects. Naftali et al. explain that they shift the balance of inflammatory cytokines and anti-inflammatory cytokines toward a T-helper cell type 2 profile and suppress cell-mediated immunity. They also antagonize release of prostaglandins, histamine, and the matrix-active proteases from mast cells.
However, studies with plant products are a challenge because it is difficult to determine the exact contribution of each constituent.
The authors dealt with this problem by using cannabis made from genetically identical plants. The equal content of active ingredients was verified in cannabis ﬂowers, and the machine-made cigarettes contained equal weights of material.
Naftali et al. chose to administer cannabis via smoking to induce a rapid increase in blood cannabinoid levels. During smoking, the acids are decarboxylated to the active free cannabinoids, which could explain why ingesting cannabis orally is less effective than smoking it.
Because of the harmful effects of smoking on the lungs, further studies are needed to determine the safety of this approach. Naftali et al. say that until further data are available, long-term medical cannabis cannot be recommended. They propose that cannabis be reserved for compassionate use, in only patients who have exhausted all other medical and surgical options.