常见大麻素类化合物药理作用及构效关系研究进展

doi:10.19803/j.1672-8629.20210549

摘要/Abstract

摘要： 近年大麻类化合物受到广泛关注,本文从国内外的研究现状出发,总结并归纳几种常见大麻素类化合物的药理作用及目前存在的问题。大麻二酚、四氢大麻酚和大麻萜酚等具有抗肿瘤、抗炎、免疫调节、抗菌、精神调节、神经保护等多种药理作用,具有潜在的临床应用价值。大麻素类化合物需重点监测和管理,防止滥用情况的发生,因此在研究其多种药理作用的同时,阐明其构效关系,将有助于减少其精神依赖性,拓展其临床应用范围。

关键词: 大麻, 大麻二酚, 四氢大麻酚, 大麻萜酚, 精神作用, 抗菌, 药理作用, 构效关系

Abstract: Cannabis compounds have attracted extensive attention in recent years. Based on the current research globally, this review summarizes the pharmacological effects and the existing problems with several common cannabinoid compounds. Cannabinol, tetrahydrocannabinol and cannabinoid phenol have diverse pharmacological effects, such as anti-tumor, anti-inflammatory, antibacterial properties, immune regulation, mental regulation as well as neuroprotection. Cannabinoid compounds need to be monitored to prevent abuse. Therefore, the relationship between the chemical structure and the pharmacological activity should be clarified to reduce mental dependence and broaden clinical applications.

Key words: Cannabis sativa L., cannabidiol, tetrahidrocannabinol, canabigerol, mental effect, antibacterial, pharmacological effect, structure-activity relationship

中图分类号:

R994.11

王椿清, 张圆圆, 李倩, 杜丽娜, 金义光. 常见大麻素类化合物药理作用及构效关系研究进展[J]. 中国药物警戒, 2022, 19(12): 1388-1392.

WANG Chunqing, ZHANG Yuanyuan, LI Qian, DU Lina, JIN Yiguang. Research progress on pharmacological effect and structure-activity relationship of common cannabinoid compounds[J]. Chinese Journal of Pharmacovigilance, 2022, 19(12): 1388-1392.

参考文献

[1] Chinese Pharmacopoeia Commission.Pharmacopoeia of the People’s Republic of China(中华人民共和国药典一部,2020年版)[M]. Beijing: China Medical Science Press,2020.
[2] GONG PH, YANG Y, LIU YT, et al.Research progress on chemical components of Cannabis Sativa and their pharmacological effects[J]. Chin J Experim Trad Med Formul(中国实验方剂学杂志), 2017, 23(13): 212-219.
[3] HILL A, WILLIAMS C, WHALLEY B, et al.Phytocannabinoids as novel therapeutic agents in CNS disorders[J]. Pharmacol & Therap, 2012, 133(1): 79-97.
[4] LI J, ZHU X, WAN H, et al.Progress on chemical constituents and analytical methods of cannabinoids in Cannabis sativa[J]. Chin Trad HerbDrugs(中草药), 2020, 51(24): 6414-6425.
[5] KAPLAN J, STELLA N, CATTERALL W, et al.Cannabidiol attenuates seizures and social deficits in a mouse model of dravet syndrome[J]. Proc National Acad Sci USA, 2017, 114(42): 11229-11234.
[6] GUGLIANDOLO A, SILVESTRO S, CHIRICOSTA L, et al.The transcriptomic analysis of NSC-34 motor neuron-like cells reveals that cannabigerol influences synaptic pathways: a comparative study with cannabidiol[J]. Life-Basel, 2020, 10(10): 227.
[7] LAPRAIRIE R, BAGHER A, KELLY M, et al.Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor[J]. Brit J Pharm, 2015, 172(20): 4790-4805.
[8] SUN YS.An overview of new drugs approved in the US and EU in June 2018[J]. Prog Pharm Sci(药学进展), 2018, 42(7): 551-553.
[9] WANG X, YU J.Antitumor effects of cannabidiol and its molecular mechanism:research advances[J]. J Int Pharm Res(国际药学研究杂志), 2020, 47(12): 1057-1061,1077.
[10] MASSI P, VACCANI A, BIANCHESSI S, et al.The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells[J]. Cell Mol Life Sci, 2006, 63(17): 2057-2066.
[11] KOZELA E, KRAWCZYK M, KOS T, et al.Cannabidiol improves cognitive impairment and reverses cortical transcriptional changes induced by ketamine in schizophrenia-like model in rats[J]. Mol Neurobiol, 2020, 57(3): 1733-1747.
[12] MAJOR-MONFRIED H, RENTERIA A, PAWARODE A, et al.MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD[J]. Blood, 2018, 131(25): 2846-2855.
[13] BETONICO BB, SOARES J, PAIVA I, et al.Cannabidiol enhances intestinal Cb2 receptor expression and activation increasing regulatory T cells and reduces murine acute graft-versus-host disease without interfering with the graft-versus-leukemia response[J]. J Pharmacol Exp Ther, 2021, 377(2): 273-283.
[14] YIN S, TANG SQ, LU Y.Research progress on mechanism of neuroprotective effects of cannabidiol[J]. Chin Trad Herb Drugs(中草药), 2014, 45(3): 432-436.
[15] GAO BB, WU YK, MA JH, et al.Neuroprotective effect of cannabidiol on acute cerebral hemorrhage in mice and its mechanism[J]. Shandong Med J(山东医药), 2017, 57(4): 34-36.
[16] ATALAY S, GEGOTEK A, WRONSKI A, et al.Therapeutic application of cannabidiol on UVA and UVB irradiated rat skin. a proteomic study[J]. J Pharm Biomed Anal, 2021, 192: 113656.
[17] MCCOY K.Interaction between cannabinoid system and Toll-like receptors controls inflammation[J]. Mediat Inflamm, 2016, 2016: 5831315.
[18] MAJDI F, TAHERI F, SALEHI P, et al.Cannabinoids delta(9)-tetrahydrocannabinol and cannabidiol may be effective against methamphetamine induced mitochondrial dysfunction and inflammation by modulation of Toll-like type-4(Toll-like 4) receptors and NF-kappa B signaling[J]. Med Hypoth, 2019, 133: 109371.
[19] MOHANNED A, ALGHETAA H, SULTAN M, et al.Administration of delta(9)-tetrahydrocannabinol (THC) post-staphylococcal enterotoxin B exposure protects mice from acute respiratory distress syndrome and toxicity[J]. Fronti Pharm, 2020, 11: 893.
[20] DI FORTI M, IYEGBE C, SALLIS H, et al.Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users[J]. Biol Psych, 2012, 72(10): 811-816.
[21] ZUARDI A, CRIPPA J, HALLAK J, et al.Cannabidiol, a cannabis sativa constituent, as an antipsychotic drug[J]. Brazil J Med Biol Res, 2006, 39(4): 421-429.
[22] SZKUDLAREK H, RODRIGUEZ-RUIZ M, HUDSON R, et al.THC and CBD produce divergent effects on perception and panic behaviours via distinct cortical molecular pathways[J]. Prog Neuro-Psychopharm & Biol Psych, 2021, 104: 110029.
[23] BHATTACHARYYA S, SAINSBURY T, ALLEN P, et al.Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of delta-9-THC[J]. Psychol Med, 2018, 48(16): 2748-2756.
[24] BEGGIATO S, IERACI A, TOMASINI M, et al.Prenatal THC exposure raises kynurenic acid levels in the prefrontal cortex of adult rats[J]. Prog in Neuro-Psychopharm & Biol Psychiatry, 2020, 100: 109883.
[25] GIBULA-TARLOWSKA E, WYDRA K, KOTLINSKA J.Deleterious effects of ethanol, delta(9)-tetrahydrocannabinol (THC), and their combination on the spatial memory and cognitive flexibility in adolescent and adult male rats in the Barnes maze task[J]. Pharmaceutics, 2020, 12(7): 654.
[26] RENARD J, RUSHLOW W, LAVIOLETTE S.Effects of adolescent THC exposure on the prefrontal GABAergic system: implications for schizophrenia-related psychopathology[J]. Front in Psychi, 2018, 9: 281.
[27] AFRIN F, CHI M, EAMENS A, et al.Can Hemp Help? Low-THC cannabis and Non-THC cannabinoids for the treatment of cancer[J]. Cancers, 2020, 12(4): 1033.
[28] LI HY, YANG CP, JIN HT.Research progress of target related toxicity of anti-tumor drugs[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2018, 15(3): 152-157.
[29] ANDREWS P, NAYLOR R, Joss R.Neuropharmacology of emesis and its relevance to anti-emetic therapy. Consensus and controversies[J]. Support Care Cancer, 1998, 6(3): 197-203.
[30] DARMAIN N, WANG Y, ABAD J, et al.Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists[J]. Brain Res, 2008, 1214: 58-72.
[31] DARMAIN N, BELKACEMI L, ZHONG W.Delta(9)-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor[J]. Eur J Pharm, 2019, 865: 172806.
[32] CHAVES C, BITTENCOURT P, PELEGRINI A.Ingestion of a THC-rich cannabis oil in people with fibromyalgia: A randomized, double-blind, placebo-controlled clinical trial[J]. Pain Med, 2020, 21(10): 2212-2218.
[33] LINHER-MELVILLE K, ZHU Y, SIDHU J, et al.Evaluation of the preclinical analgesic efficacy of naturally derived, orally administered oil forms of Delta 9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their 1:1 combination[J]. PLOS One, 2020, 15(6): e0234176.
[34] ATWAL N, CASSEY S, MITCHELL V, et al.THC and gabapentin interactions in a mouse neuropathic pain model[J]. Neuropharm, 2019, 144: 115-121.
[35] GIACOPPO S, BRAMANTI P, MAZZON E.Sativex in the management of multiple sclerosis-related spasticity: an overview of the last decade of clinical evaluation[J]. Multip Scler and Related Disord, 2017, 17: 22-31.
[36] LYU Y, KOPCHO S, MOHAN M, et al.Long-term low-dose delta-9-tetrahydrocannbinol (THC) administration to simian immunodeficiency virus (SIV) infected rhesus macaques stimulates the release of bioactive blood extracellular vesicles (EVs) that induce divergent structural adaptations and signaling cues[J]. Cells, 2020, 9(10): 2243.
[37] NACHNANI R, RAUP-KONSAVAGE W, VRANA K.The pharmacological case for cannabigerol[J]. J Pharm Exper Therap, 2021, 376(2): 204-212.
[38] CASCIO M, GAUSON L, STEVENSON L, et al.Evidence that the plant cannabinoid cannabigerol is a highly potent alpha(2)-adrenoceptor agonist and moderately potent 5HT(1A) receptor antagonist[J]. Brit J Pharm, 2010, 159(1): 129-141.
[39] DI GIACOMO V, CHIAVAROLI A, ORLANDO G, et al.Neuroprotective and neuromodulatory effects induced by cannabidiol and cannabigerol in rat Hypo-E22 cells and isolated hypothalamus[J]. Antioxid, 2020, 9(1): 71.
[40] HUI RS, YANG XQ.Cannabis and fungal infections[J]. Chin J Mycol(中国真菌学杂志), 2009, 4(5): 317-320.
[41] PINZI L, LHERBET C, BALTAS M, et al.In silico repositioning of cannabigerol as a novel inhibitor of the enoyl acyl carrier protein (ACP) reductase (InhA)[J]. Molecules, 2019, 24(14): 2567.
[42] FENG JZ, LIU SH, FENG JF, et al.Research progress on the causes and preventions of metabolic syndrome[J]. J Inner Mongolia Univ Nationalities (Nat Sci)(内蒙古民族大学学报自然科学版), 2020, 35(6): 525-528.
[43] ESPOSITO G, SCUDERI C, VALENZA M, et al.Cannabidiol reduces Ab- induced neuroinflammation and promotes hippocampal neurogenesis through PPAR gamma involvement[J]. PLOS One, 2011, 6(12): e28668.
[44] D’ANIELLO E, FELLOUS T, IANNOTTI F, et al. Identification and characterization of phytocannabinoids as novel dual PPAR alpha/gamma agonists by a computational and in vitro experimental approach[J]. Biochim Et Biophys Acta-General Subj, 2019, 1863(3): 586-597.
[45] BORRELLI F, FASOLINO I, ROMANO B, et al.Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease[J]. Biochem Pharm, 2013, 85(9): 1306-1316.
[46] PAGANO E, IANNOTTI F, PISCITELLI F, et al.Efficacy of combined therapy with fish oil and phytocannabinoids in murine intestinal inflammation[J]. Phytother Res, 2021, 35(1): 517-529.
[47] LAH T, NOVAK M, ALMIDON M, et al.Cannabigerol is a potential therapeutic agent in a novel combined therapy for glioblastoma[J]. Cells, 2021, 10(2): 340.