McCarberg Bill H, Barkin Robert L
Family Medicine Kaiser Permanente, Escondido, California, USA.
Am J Ther. 2007 Sep-Oct;14(5):475-83. doi: 10.1097/MJT.0b013e3180a5e581.
For thousands of years, physicians and their patients employed cannabis as a therapeutic agent. Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed. However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored. Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies. Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions. Nevertheless, despite promising preclinical and early clinical data, particularly in the areas of inflammation and nociception, development challenges abound. Tetrahydrocannabinol (THC) and other CB1 receptor agonists can have an undesirable CNS impact, and, in many cases, dose optimization may not be realizable before onset of excessive side effects. In addition, complex botanically derived cannabinoid products must satisfy the demanding criteria of the U.S. Food and Drug Association's approval process. Recent agency guidance suggests that these obstacles are not insurmountable, although cannabis herbal material ("medical marijuana") may present fatal uncertainties of quality control and dosage standardization. Therefore, formulation, composition, and delivery system issues will affect the extent to which a particular cannabinoid product may have a desirable risk-benefit profile and acceptable abuse liability potential. Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders. Further research is warranted to explore the therapeutic potential of this area.
数千年来，医生及其患者一直将大麻用作治疗药物。尽管有如此广泛的历史使用情况，但在西方世界，大麻在医学专业人员中失宠，因为19世纪和20世纪初可用的技术无法开发出可靠、标准化的制剂。然而，自20世纪90年代发现并克隆大麻素受体（CB1和CB2）以来，该领域的科学兴趣迅速增长，人们积极探索这个迷人的受体系统及其内源性配体的复杂性。最近的研究表明，大麻素具有丰富的药理学特性，可能与许多其他受体系统以及其他大麻素相互作用，从而产生潜在的协同作用。大麻素——内源性大麻素、植物大麻素和合成大麻素——影响众多身体功能，并在一些严重疾病中显示出不同程度的疗效。然而，尽管临床前和早期临床数据很有前景，特别是在炎症和疼痛领域，但开发挑战依然众多。四氢大麻酚（THC）和其他CB1受体激动剂可能会对中枢神经系统产生不良影响，而且在许多情况下，在出现过多副作用之前可能无法实现剂量优化。此外，复杂的植物源性大麻素产品必须满足美国食品药品监督管理局审批程序的严格标准。该机构最近的指导意见表明，这些障碍并非无法克服，尽管大麻草药材料（“医用大麻”）可能存在质量控制和剂量标准化方面的致命不确定性。因此，制剂、成分和给药系统问题将影响特定大麻素产品具有理想的风险效益比和可接受的滥用可能性的程度。大麻素受体激动剂和/或影响内源性大麻素合成、代谢和转运调节的分子，未来可能为治疗许多目前难以治疗的疾病提供极其有价值的工具。有必要进行进一步研究以探索该领域的治疗潜力。
