Archive for the ‘Crohns/IBS’ Category

Cannabis has been used to treat gastrointestinal (GI) conditions that range from enteric infections and inflammatory conditions to disorders of motility, emesis and abdominal pain. The mechanistic basis of these treatments emerged after the discovery of Delta(9)-tetrahydrocannabinol as the major constituent of Cannabis. Further progress was made when the receptors for Delta(9)-tetrahydrocannabinol were identified as part of an endocannabinoid system, that consists of specific cannabinoid receptors, endogenous ligands and their biosynthetic and degradative enzymes. Anatomical, physiological and pharmacological studies have shown that the endocannabinoid system is widely distributed throughout the gut, with regional variation and organ-specific actions. It is involved in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation and cell proliferation in the gut. Cellular targets have been defined that include the enteric nervous system, epithelial and immune cells. Molecular targets of the endocannabinoid system include, in addition to the cannabinoid receptors, transient receptor potential vanilloid 1 receptors, peroxisome proliferator-activated receptor alpha receptors and the orphan G-protein coupled receptors, GPR55 and GPR119. Pharmacological agents that act on these targets have been shown in preclinical models to have therapeutic potential. Here, we discuss cannabinoid receptors and their localization in the gut, the proteins involved in endocannabinoid synthesis and degradation and the presence of endocannabinoids in the gut in health and disease. We focus on the pharmacological actions of cannabinoids in relation to GI disorders, highlighting recent data on genetic mutations in the endocannabinoid system in GI disease. Copyright 2010 Elsevier Inc. All rights reserved.

Excessive inflammatory responses can emerge as a potential danger for organisms’ health. Physiological balance between pro- and anti-inflammatory processes constitutes an important feature of responses against harmful events. Here, we show that cannabinoid receptors type 1 (CB1) mediate intrinsic protective signals that counteract proinflammatory responses. Both intrarectal infusion of 2,4-dinitrobenzene sulfonic acid (DNBS) and oral administration of dextrane sulfate sodium induced stronger inflammation in CB1-deficient mice (CB1^–/–) than in wild-type littermates (CB1^+/+). Treatment of wild-type mice with the specific CB1 antagonist N-(piperidino-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-pyrazole-3-carboxamide (SR141716A) mimicked the phenotype of CB1^–/– mice, showing an acute requirement of CB1 receptors for protection from inflammation. Consistently, treatment with the cannabinoid receptor agonist R(-)-7-hydroxy-Δ⁶-tetra-hydrocannabinol-dimethylheptyl (HU210) or genetic ablation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) resulted in protection against DNBS-induced colitis. Electrophysiological recordings from circular smooth muscle cells, performed 8 hours after DNBS treatment, revealed spontaneous oscillatory action potentials in CB1^–/– but not in CB1^+/+ colons, indicating an early CB1-mediated control of inflammation-induced irritation of smooth muscle cells. DNBS treatment increased the percentage of myenteric neurons expressing CB1 receptors, suggesting an enhancement of cannabinoid signaling during colitis. Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses.

Patients with Crohn’s disease report subjective benefits from cannabis, including pain relief and increased appetite, according to survey data published in the autumn issue of O’Shaughnessy’s: The Journal of Cannabis in Clinical Practice.

Twelve patients were self-selected to participate in the survey, which assessed subjective changes in volunteers’ symptoms after the use of cannabis. “For all signs and symptoms evaluated in the study, the patients described marked improvements with the use of cannabis,” concluded co-author Jeff Hergenrather of the California Society for Cannabis Clinicians. “Beneficial effects were reported for appetite, pain, nausea, vomiting, fatigue, activity, and depression. Patients also reported that cannabis use resulted in weight gain, fewer stools per day and fewer flare-ups of less severity.”

Authors also found that patients’ use of cannabis was associated with a decrease in their use of other pharmaceutical medicines.

The pilot study is the first to examine the therapeutic use of cannabis in patients with Crohn’s disease.

Pre-clinical data published this past summer in the journal Gastroenterology found that cannabinoids may promote healing of the gastrointestinal membrane, and could offer relief to patients suffering from inflammatory disorders such as Crohn’s disease and ulcerative colitis. Previous trials in animals have demonstrated that the activation of cannabinoid receptors in the gastrointestinal tract protects the body from inflammation and modulates gastric secretions and intestinal motility, among other functions.