Aviello G, Romano B, Izzo A A
Department of Experimental Pharmacology and Endocannabinoid Research Group, University of Naples Federico II, Naples, Italy.
Eur Rev Med Pharmacol Sci. 2008 Aug;12 Suppl 1:81-93.
The plant Cannabis has been known for centuries to be beneficial in a variety of gastrointestinal diseases, including emesis, diarrhea, inflammatory bowel disease and intestinal pain. delta9-tetrahydrocannabinol, the main psychotropic component of Cannabis, acts via at least two types of cannabinoid receptors, named CB1 and CB2 receptors. CB1 receptors are located primarily on central and peripheral neurons (including the enteric nervous system) where they modulate neurotransmitter release, whereas CB2 receptors are concerned with immune function, inflammation and pain. The discovery of endogenous ligands [i.e. anandamide and 2-arachidonoyl glycerol (2-AG)] for these receptors indicates the presence of a functional endogenous cannabinoid system in the gastrointestinal tract. Anatomical and functional evidence suggests the presence of CB1 receptors in the myenteric plexus, which are associated with cholinergic neurons in a variety of species, including in humans. Activation of prejunctional CB1 receptors reduces excitatory enteric transmission (mainly cholinergic transmission) in different regions of the gastrointestinal tract. Consistently, in vivo studies have shown that cannabinoids reduce gastrointestinal transit in rodents through activation of CB1, but not CB2, receptors. However, in pathophysiological states, both CB1 and CB2 receptors could reduce the increase of intestinal motility induced by inflammatory stimuli. Cannabinoids also reduce gastrointestinal motility in randomized clinical trials. Overall, modulation of the gut endogenous cannabinoid system may provide a useful therapeutic target for disorders of gastrointestinal motility.
几个世纪以来，人们都知道植物大麻对多种胃肠道疾病有益，包括呕吐、腹泻、炎症性肠病和肠道疼痛。大麻的主要精神活性成分Δ9-四氢大麻酚通过至少两种类型的大麻素受体发挥作用，即CB1和CB2受体。CB1受体主要位于中枢和外周神经元（包括肠神经系统）上，在这些部位它们调节神经递质的释放，而CB2受体则与免疫功能、炎症和疼痛有关。这些受体的内源性配体（即花生四烯乙醇胺和2-花生四烯酸甘油酯（2-AG））的发现表明胃肠道中存在功能性内源性大麻素系统。解剖学和功能学证据表明，肌间神经丛中存在CB1受体，在包括人类在内的多种物种中，这些受体与胆碱能神经元相关。突触前CB1受体的激活会减少胃肠道不同区域的兴奋性肠内传递（主要是胆碱能传递）。同样，体内研究表明，大麻素通过激活CB1而非CB2受体来减少啮齿动物的胃肠蠕动。然而，在病理生理状态下，CB1和CB2受体都可以减少炎症刺激引起的肠道蠕动增加。在随机临床试验中，大麻素也会降低胃肠蠕动。总体而言，调节肠道内源性大麻素系统可能为胃肠动力障碍提供一个有用的治疗靶点。
