Application Prospect of Mannabidiol in Medicine
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摘要: 大麻中具有药用价值的主要成分是Δ9-四氢大麻酚(Δ9-THC)和大麻二酚(CBD),其中CBD因不能直接激活大麻素1型受体(CB1R)和大麻素2型受体(CB2R)而不具有精神活性和药物依赖性,安全性相对高。CBD作为主要的大麻素提取物,证实具有镇痛、镇静、抗炎、抗惊厥、改善睡眠、抗焦虑、抗精神病、抗风湿、保护皮肤屏障、抗细胞凋亡和神经保护等作用。本综述旨在总结CBD在临床疾病治疗中的应用现状,为今后CBD相关药物在治疗癫痫、神经病理性疼痛、焦虑症和抑郁症、肿瘤、皮肤、代谢相关疾病的应用提供新思路。Abstract: The main components of cannabis with medicinal value are Δ9-tetrahydrocannabinol(Δ9-THC)and cannabidiol(CBD), of which CBD cannot directly activate cannabinoid type 1 receptor(CB1R)and cannabinoid type 2 receptors. Body(CB2R)does not have psychoactive and drug dependence, and its safety is relatively high. CBD, as the main cannabinoid extract, has proven to have analgesic, sedative, anti-inflammatory, anti-convulsant, sleep-improving, anti-anxiety, anti-psychotic, anti-rheumatic, skin barrier, anti-apoptotic and neuroprotective effects. This review aims to summarize the application status of CBD in the treatment of clinical diseases, and provide new ideas for the future application of CBD-related drugs in the treatment of epilepsy, neuropathic pain, anxiety and depression, tumors, skin, and metabolism-related diseases.
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Key words:
- Cannabidiol /
- Clinical application /
- Neuroprotection
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[1] Devinsky O,Marsh E,Friedman D,et al. Cannabidiol in patients with treatment-resistant epilepsy:an open-label interventional trial[J]. The Lancet Neurology,2016,15(3):270-278. doi: 10.1016/S1474-4422(15)00379-8 [2] Stockings E,Zagic D,Campbell G,et al. Evidence for cannabis and cannabinoids for epilepsy:a systematic review of controlled and observational evidence[J]. Journal of Neurology,Neurosurgery,and Psychiatry,2018,89(7):741-753. doi: 10.1136/jnnp-2017-317168 [3] Rosenberg E C,Louik J,Conway E,et al. Quality of life in childhood epilepsy in pediatric patients enrolled in a prospective,open-label clinical study with cannabidiol[J]. Epilepsia,2017,58(8):e96-e100. doi: 10.1111/epi.13815 [4] Ferreira-junior N C,Campos A C,Guimarães F S,et al. Biological bases for a possible effect of cannabidiol in Parkinson's disease[J]. Revista Brasileira de Psiquiatria (Sao Paulo,Brazil :1999),2020,42(2):218-224. doi: 10.1590/1516-4446-2019-0460 [5] Junior N C F,Dos-santos-pereira M,Guimarães F S,et al. Cannabidiol and cannabinoid compounds as potential strategies for treating parkinson's disease and L-DOPA-Induced dyskinesia[J]. Neurotoxicity Research,2020,37(1):12-29. doi: 10.1007/s12640-019-00109-8 [6] Balash Y,Bar-lev schleider L,Korczyn A D,et al. Medical cannabis in parkinson disease:Real-Life patients' experience[J]. Clinical Neuropharmacology,2017,40(6):268-272. doi: 10.1097/WNF.0000000000000246 [7] Khan F,Amatya B. Rehabilitation in multiple sclerosis:A systematic review of systematic reviews[J]. Archives of Physical Medicine and Rehabilitation,2017,98(2):353-367. doi: 10.1016/j.apmr.2016.04.016 [8] López-sendón moreno J L,García caldentey J,Trigo cubillo P,et al. A double-blind,randomized,cross-over,placebo-controlled,pilot trial with Sativex in Huntington's disease[J]. Journal of Neurology,2016,263(7):1390-1400. doi: 10.1007/s00415-016-8145-9 [9] Clément T,Rodriguez-grande B,Badaut J. Aquaporins in brain edema[J]. Journal of Neuroscience Research,2020,98(1):9-18. doi: 10.1002/jnr.24354 [10] Hayakawa K,Irie K,Sano K,et al. Therapeutic time window of cannabidiol treatment on delayed ischemic damage via high-mobility group box1-inhibiting mechanism[J]. Biological & Pharmaceutical Bulletin,2009,32(9):1538-1544. [11] 高兵兵,吴月奎,马建华,等. 大麻二酚对急性脑出血小鼠的神经保护作用及其机制[J]. 山东医药,2017,57(4):34-36. doi: 10.3969/j.issn.1002-266X.2017.04.010 [12] Mandolini G M,Lazzaretti M,Pigoni A,et al. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders:a critical overview[J]. Epidemiology and Psychiatric Sciences,2018,27(4):327-335. doi: 10.1017/S2045796018000239 [13] Zanelati T V,Biojone C,Moreira F A,et al. Antidepressant-like effects of cannabidiol in mice:possible involvement of 5-HT1A receptors[J]. British Journal of Pharmacology,2010,159(1):122-128. doi: 10.1111/j.1476-5381.2009.00521.x [14] Ceskova E,Silhan P. Novel treatment options in depression and psychosis[J]. Neuropsychiatric Disease and Treatment,2018,14(1):741-747. [15] Silote G P,Sartim A,Sales A,et al. Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms[J]. Journal of Chemical Neuroanatomy,2019,98(4):104-116. [16] Statter M B,Hirschl R B,Coran A C. Inflammatory bowel disease[J]. Pediatric Clinics of North America,1993,40:1213-1231. [17] De filippis D,Iuvone T,D'amico A,et al. Effect of cannabidiol on sepsis-induced motility disturbances in mice:involvement of CB receptors and fatty acid amide hydrolase[J]. Neurogastroenterology and Motility :The official Journal of the European Gastrointestinal Motility Society,2008,20(8):919-927. doi: 10.1111/j.1365-2982.2008.01114.x [18] Chen G Y,Cao H X,Li F,et al. New risk-scoring system including non-alcoholic fatty liver disease for predicting incident type 2 diabetes in east China:Shanghai baosteel cohort[J]. Journal of diabetes investigation,2016,7(2):206-211. doi: 10.1111/jdi.12395 [19] Wang Y,Mukhopadhyay P,Cao Z,et al. Cannabidiol attenuates alcohol-induced liver steatosis,metabolic dysregulation,inflammation and neutrophil-mediated injury[J]. Scientific Reports,2017,7(1):12064. doi: 10.1038/s41598-017-10924-8 [20] 郭蓉,陈璇,郭鸿彦. 四氢大麻酚和大麻二酚的药理研究进展[J]. 天然产物研究与开发,2017,29(8):1449-1453. [21] Wang Y,Mukhopadhyay P,CAO Z,et al. Cannabidiol protects against chronic plus binge alcohol induced liver injury by modulating neutrophil infiltration,E selectin,inflammation and oxidative/nitrative stress[J]. Free Radical Biology & Medicine,2014,76(12):S88. [22] Ignatowska-jankowska B,Jankowski M M,Swiergiel A H. Cannabidiol decreases body weight gain in rats:involvement of CB2 receptors[J]. Neuroscience Letters,2011,490(1):82-84. doi: 10.1016/j.neulet.2010.12.031 [23] Yang L,Rozenfeld R,Wu D,et al. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy[J]. Free Radic Biol Med,2014,68(3):260-267. [24] Silvestri C,Paris D,Martella A,et al. Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis[J]. Journal of Hepatology,2015,62(6):1382-1390. doi: 10.1016/j.jhep.2015.01.001 [25] 陈瑞,高晓刚,张雷,等. 大麻二酚对大鼠非酒精性脂肪肝的治疗作用及机制[J]. 解放军医学杂志,2017,42(6):515-519. doi: 10.11855/j.issn.0577-7402.2017.06.07 [26] 常丽,李建军,黄思齐,等. 植物大麻活性成分及其药用研究概况[J]. 生命的化学,2018,38(2):273-280. [27] 韦凤,涂冬萍,王柳萍. 火麻仁食用开发和药理作用研究进展[J]. 中国老年学,2015,35(12):3486-3488. [28] Oláh A,Tóth B I,Borbíró I,et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes[J]. The Journal of Clinical Investigation,2014,124(9):3713-3724. doi: 10.1172/JCI64628 [29] Petrosino S,Verde R,Vaia M,et al. Anti-inflammatory properties of cannabidiol,a nonpsychotropic cannabinoid,in experimental allergic contact dermatitis[J]. The Journal of Pharmacology and Experimental Therapeutics,2018,365(3):652-663. doi: 10.1124/jpet.117.244368 [30] Wilkinson J D,Williamson E M. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis[J]. Journal of Dermatological Science,2007,45(2):87-92. doi: 10.1016/j.jdermsci.2006.10.009 [31] Walsh S K,Hepburn C Y,Kane K A,et al. Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion[J]. British Journal of Pharmacology,2010,160(5):1234-1242. doi: 10.1111/j.1476-5381.2010.00755.x [32] Durst R,Danenberg H,Gallily R,et al. Cannabidiol,a nonpsychoactive cannabis constituent,protects against myocardial ischemic reperfusion injury[J]. American Journal of Physiology Heart and Circulatory Physiology,2007,293(6):H3602-3607. doi: 10.1152/ajpheart.00098.2007 [33] Feng Y,Chen F,Yin T,et al. Pharmacologic effects of cannabidiol on acute reperfused myocardial infarction in rabbits:Evaluated with 3.0T cardiac magnetic resonance imaging and histopathology[J]. Journal of Cardiovascular Pharmacology,2015,66(4):354-363. doi: 10.1097/FJC.0000000000000287 [34] Stanley C P,Hind W H,O'sullivan S E. Is the cardiovascular system a therapeutic target for cannabidiol[J]. British Journal of Clinical Pharmacology,2013,75(2):313-322. doi: 10.1111/j.1365-2125.2012.04351.x [35] 孙姣卓,王雄,张萍. 大麻二酚对大鼠心肌缺血/再灌注损伤的保护作用和机制[J]. 中西医结合心脑血管病杂志,2016,14(2):133-137. doi: 10.3969/j.issn.1672-1349.2016.02.008 [36] Blair R E,Deshpande L S,Delorenzo R J. Cannabinoids:is there a potential treatment role in epilepsy[J]. Expert Opinion on Pharmacotherapy,2015,16(13):1911-1914. doi: 10.1517/14656566.2015.1074181 [37] Ribeiro A,Ferraz-de-paula V,Pinheiro M L,et al. Cannabidiol,a non-psychotropic plant-derived cannabinoid,decreases inflammation in a murine model of acute lung injury:role for the adenosine A(2A) receptor[J]. European Journal of Pharmacology,2012,678(1-3):78-85. doi: 10.1016/j.ejphar.2011.12.043 [38] 叶程龙余,莫斯喻,等. 大麻二酚对应激大鼠肺部损伤的预防保护作用[J]. 广东药学院学报,2019,35(2):234-237. [39] JAcobsson S O,Rongård E,Stridh M,et al. Serum-dependent effects of tamoxifen and cannabinoids upon C6 glioma cell viability[J]. Biochemical Pharmacology,2000,60(12):1807-1813. doi: 10.1016/S0006-2952(00)00492-5 [40] Massi P,Vaccani A,Bianchessi S,et al. The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells[J]. Cellular and Molecular Life Sciences :CMLS,2006,63(17):2057-2066. doi: 10.1007/s00018-006-6156-x [41] Shrivastava A,Kuzontkoski P M,Groopman J E,et al. Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy[J]. Molecular Cancer Therapeutics,2011,10(7):1161-1172. doi: 10.1158/1535-7163.MCT-10-1100 [42] Elbaz M,Nasser M W,Ravi J,et al. Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway:novel anti-tumor mechanisms of cannabidiol in breast cancer[J]. Molecular Oncology,2015,9(4):906-919. doi: 10.1016/j.molonc.2014.12.010 [43] Haustein M,Ramer R,Linnebacher M,et al. Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1[J]. Biochemical pharmacology,2014,92(2):312-325. doi: 10.1016/j.bcp.2014.07.014 [44] Solinas M,Massi P,Cantelmo A R,et al. Cannabidiol inhibits angiogenesis by multiple mechanisms[J]. British Journal of Pharmacology,2012,167(6):1218-1231. doi: 10.1111/j.1476-5381.2012.02050.x [45] Simmerman E,Qin X,Yu J C,et al. Cannabinoids as a potential new and novel treatment for melanoma:A pilot study in a murine model[J]. The Journal of Surgical Research,2019,235(3):210-215. [46] Chelliah M P,Zinn Z,Khuu P,et al. Self-initiated use of topical cannabidiol oil for epidermolysis bullosa[J]. Pediatric Dermatology,2018,35(4):e224-e227. doi: 10.1111/pde.13545 [47] Weiss L,Zeira M,Reich S,et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice[J]. Autoimmunity,2006,39(2):143-151. doi: 10.1080/08916930500356674 [48] Weiss L,Zeira M,Reich S,et al. Cannabidiol arrests onset of autoimmune diabetes in NOD mice[J]. Neuropharmacology,2008,54(1):244-249. doi: 10.1016/j.neuropharm.2007.06.029 [49] Huestis M A,Solimini R,Pichini S,et al. Cannabidiol adverse effects and toxicity[J]. Current Neuropharmacology,2019,17(10):974-989. doi: 10.2174/1570159X17666190603171901
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