Cannabis, Cannabinoids, and the Endocannabinoid System-Is there Therapeutic Potential for Inflammatory Bowel Disease?

Abstract

Cannabis sativa and its extracts have been used for centuries, both medicinally and recreationally. There is accumulating evidence that exogenous cannabis and related cannabinoids improve symptoms associated with inflammatory bowel disease [IBD], such as pain, loss of appetite, and diarrhoea. In vivo, exocannabinoids have been demonstrated to improve colitis, mainly in chemical models. Exocannabinoids signal through the endocannabinoid system, an increasingly understood network of endogenous lipid ligands and their receptors, together with a number of synthetic and degradative enzymes and the resulting products. Modulating the endocannabinoid system using pharmacological receptor agonists, genetic knockout models, or inhibition of degradative enzymes have largely shown improvements in colitis in vivo. Despite these promising experimental results, this has not translated into meaningful benefits for human IBD in the few clinical trials which have been conducted to date, the largest study being limited by poor medication tolerance due to the Δ9-tetrahydrocannabinol component. This review article synthesises the current literature surrounding the modulation of the endocannabinoid system and administration of exocannabinoids in experimental and human IBD. Findings of clinical surveys and studies of cannabis use in IBD are summarised. Discrepancies in the literature are highlighted together with identifying novel areas of interest.

Keywords: Inflammatory bowel disease; cannabinoids; cannabis.

Figure 1.

A summary of existing studies of the endocannabinoid tone in human ileum and colon in health and IBD. Studies of the ECS in human IBD have yielded conflicting results dependent on the technique used, the site of sampling [ileum vs colon], and the comparison used [inflamed vs non-inflamed vs healthy]. Only one study has assessed the synthetic [DAGL] and key hydrolytic [MGLL] enzyme involved in 2AG metabolism. No studies have examined the presence of ABHD6 or 12. Data extracted from references 48, 51–59. IBD, inflammatory bowel disease; ECS, endocannabinoid system.

Figure 2.

A summary of clinical studies and trials of cannabis and cannabinoids in human IBD. Studies consistently demonstrate use of cannabis in patients with IBD, frequently for symptom relief. As yet, no clinical trials of cannabinoids in IBD have met their primary endpoints but demonstrate improvements in symptoms, quality of life, and clinical severity scores. Data extracted from references 60, 116–124, 126, 128. IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis; OR, odds ratio; HBI, Harvey-Bradshaw Index; CDAI, Crohn’s Disease Activity Index; QoL, quality of life; CBD, cannabidiol; CBD BDS, cannabidiol botanical drug substance; THC, tetrahydrocannabinol; PP, per protocol; RCT, randomised-controlled trial; ns, not significant.