Department of Pathology, Microbiology and Immunology, University of South Carolina, Columbia, 29209, USA.
Trends Pharmacol Sci. 2010 Aug;31(8):345-50. doi: 10.1016/j.tips.2010.05.006. Epub 2010 Jun 28.
Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties. Significant clinical and experimental data on the use of cannabinoids as anti-inflammatory agents exist in many autoimmune disease settings, but virtually no studies have been undertaken on their potential role in transplant rejection. Here we suggest a theoretical role for the use of cannabinoids in preventing allograft rejection. The psychotropic properties of CB1 agonists limit their clinical use, but CB2 agonists may offer a new avenue to selectively target immune cells involved in allograft rejection. Moreover, development of mixed CB1/CB2 agonists that cannot cross the blood-brain barrier may help prevent their undesired psychotropic properties. In addition, manipulation of endocannabinoids in vivo by activating their biosynthesis and inhibiting cellular uptake and metabolism may offer another pathway to regulate immune response during allograft rejection.
大麻素因其免疫抑制特性而成为治疗炎症和自身免疫性疾病的有力药物候选物。在许多自身免疫性疾病情况下,都有大量关于大麻素作为抗炎药物使用的临床和实验数据,但实际上,关于它们在移植排斥反应中的潜在作用的研究几乎没有。在这里,我们提出了大麻素在预防同种异体排斥反应中的理论作用。CB1 激动剂的精神活性限制了它们的临床应用,但 CB2 激动剂可能为选择性靶向参与同种异体排斥反应的免疫细胞提供了新途径。此外,开发不能穿过血脑屏障的混合 CB1/CB2 激动剂可能有助于防止其不良的精神活性。此外,通过激活其生物合成以及抑制细胞摄取和代谢来在体内操纵内源性大麻素可能提供另一种途径来调节同种异体移植排斥反应期间的免疫反应。