The past decade has seen a constant rise in publications dealing with the anti-inflammatory effects of cannabinoids and the potential underlying mechanisms. Preclinical data on the ameliorating effect of synthetic and natural cannabinoids in animal models mimicking features of IBD have been rapidly evolving. The reasonable idea that cannabinoids would also be beneficial in IBD patients was mainly based on results from experiments in cannabinoid receptor knock-out mice and on data using cannabinoid receptor agonists and antagonists.
In 2011, a retrospective, observational study examining disease activity, use of medication, need for surgery and hospitalisation before and after cannabis use in 30 patients (26 males) with Crohn’s Disease and a questionnaire performed by a different group of patients with Ulcerative Colitis (100) and Crohn’s Disease (191), both revealed symptom relief and improvement after use of cannabis. 21 out of 30 of the study individuals reported significant improvement, with patients requiring steroid treatment reduced from 26 to 4.
A prospective trial in Israel showed complete remission in five of eleven patients suffering Crohn’s Disease who were given cannabis twice daily. Authors of the study said it had been reported for years that cannabis lessened the painful symptoms of the inflammatory bowel disease, but the findings had not been proven in a controlled trial. The study, published in Clinical Gastroenterology and Hepatology in 2013, compared 21 patients who did not respond to conventional treatment. Half were given cannabis cigarettes and the other half were given a placebo; cannabis cigarettes with the tetrahydrocannabinol (THC) removed. The results showed improvement in the group treated with the THC-intact cannabis. Those subjects also reported improved sleep and appetite.
The 8-week treatment with THC-rich cannabis caused a decrease in the Crohn’s Disease activity index in 90% of patients without producing significant side effects. The mechanisms involved most likely include peripheral actions on cannabinoid receptors 1 and 2 (CB1 and CB2) and may also include central actions. The authors rightfully concluded that a larger patient group is warranted for future studies.
The discovery of cannabinoid receptors and endogenous molecules activating these receptors led to the description of a coordinated network that is inherent to the mammalian organism, the Endocannabinoid System (ECS). This system consists of the canonical cannabinoid receptors (CB1, CB2), their endogenous ligands, anandamide and 2-arachidonoyl glycerol (2-AG), also called endocannabinoids and their synthesising and degrading enzymes. What capsaicin, the pungent ingredient of chilli, is for vanilloid receptors and morphine for opioid receptors, THC is for cannabinoid receptors; the predominant herbal ligand. Thus, THC mimics the actions of anandamide and 2-AG.
The wall of the gastrointestinal tract houses all components of the ECS. Data from 2011 showed that these components are differentially expressed in human IBD indicating a regulatory role in the disease progression. While anandamide and its synthesising enzyme display lower levels in Ulcerative Colitis, expression of CB2 receptors and enzymes responsible for synthesis and degradation of 2-AG were increased (from data in 2009). The findings indicate that the CB2 receptor plays a key role in the ameliorating effect of cannabinoids in IBD. The precise mechanism as to how cannabinoids contribute to the improvement of IBD, however, is not clear but by use of experimental models of intestinal inflammation we are able to define a picture on how and at which targets cannabinoids cause improvement of inflammation.
The primary mechanisms through which cannabis exhibits healing properties in Crohn’s Disease are its immuno-modulatory and anti-inflammatory properties: