关键词： 2-AG, 2-arachidonoylglycerol ABHD12, α-β-hydrolase domain-containing 12 ABHD6, α-β-hydrolase domain-containing 6 AEA, N-arachidonoylethanolamine AEs, adverse effects Antiretroviral BCP, β-caryophyllene CB1R, cannabinoid type 1 receptor CB2R, cannabinoid type 2 receptor CBD, cannabidiol CBDV, cannabidivarin CBRs, cannabinoid receptors CINP, chemotherapy-induced neuropathic pain CNS, central nervous system COX, cyclooxygenase Cannabinoid Cannabis DAG, diacylglycerol DAGL, DAG lipase DDS, descriptor differential scale DSP, distal symmetric polyneuropathy ECS, endocannabinoid system Endocannabinoid FAAH, fatty acid amide hydrolase FDA, Food and Drug Administration GPCRs, G protein-coupled receptors HIV, human immunodeficiency virus HIV-DSP, HIV-distal symmetric polyneuropathy HIV-NP, HIV-associated neuropathic pain Human immunodeficiency virus IPM, indomethacin plus minocycline L-29, palmitoylallylamide MAGL, monoacylglycerol lipase MAIDS, murine acquired immunodeficiency syndrome NAPE, N-acyl-phosphatidylethanolamine NAPE-PLD, NAPE-specific phospholipase D NP, neuropathic pain NSAIDs, non-steroidal anti-inflammatory drugs Neuropathic pain OTC, over the counter PLWH, people living with HIV PNP, peripheral neuropathic pain RCTs, randomised clinical trials SAMRC, South African Medical Research Council TRPA, transient receptor potential ankyrin TRPV, transient receptor potential vanilloid WHO, World Health Organization ddC, 2′-3′-dideoxycytidine delta-9-THC, delta-9-tetrahydrocannabinol gp, glycoprotein

来  源：   DOI：10.1016/j.ibneur.2021.01.004   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
Human immunodeficiency virus (HIV) infection and antiretroviral therapy can independently induce HIV-associated neuropathic pain (HIV-NP). There is a dearth of drugs or therapeutic modalities that can alleviate HIV-NP. Smoked cannabis has been reported to improve pain measures in patients with neuropathic pain. Cannabis, phytocannabinoids, and the endocannabinoids such N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), produce some of their effects via cannabinoid receptors (CBRs). Endocannabinoids are degraded by various enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase. We searched PubMed, Google Scholar, clinicaltrials.gov and clinicaltrialsregister.eu using various key words and their combinations for published papers that studied HIV-NP and cannabis, cannabinoids, or endocannabinoids up to 27th December 2020. All original research articles that evaluated the efficacy of molecules that modulate the endocannabinoid system (ECS) for the prevention and/or treatment of pain in HIV-NP animal models and patients with HIV-NP were included. The PubMed search produced a total of 117 articles, whereas the Google Scholar search produced a total of 9467 articles. Amongst the 13 articles that fulfilled the inclusion criteria 11 articles were found in both searches whereas 2 articles were found in Google Scholar only. The clinicaltrials.gov and clinicaltrialsregister.eu searches produced five registered trials of which three were completed and with results. Ten preclinical studies found that the endocannabinoids (2-AG and AEA), synthetic mixed CB1R/CB2R agonist WIN 55,212-2, a CB2R-selective phytocannabinoid β-caryophyllene, synthetic CB2R-selective agonists (AM1710, JWH015, JWH133 and Gp1a, but not HU308); FAAH inhibitors (palmitoylallylamide, URB597 and PF-3845) and a drug combination of indomethacin plus minocycline, which produces its effects in a CBR-dependent manner, either prevented the development of and/or attenuated established HIV-NP. Two clinical trials demonstrated greater efficacy of smoked cannabis over placebo in alleviating HIV-NP, whereas another clinical trial demonstrated that cannabidivarin, a cannabinoid that does not activate CBRs, did not reduce HIV-NP. The available preclinical results suggest that targeting the ECS for prevention and treatment of HIV-NP is a plausible therapeutic option. Clinical evidence shows that smoked cannabis alleviates HIV-NP. Further research is needed to find out if non-psychoactive drugs that target the ECS and are delivered by other routes than smoking could be useful as treatment options for HIV-NP.
摘要：
人类免疫缺陷病毒（HIV）感染和抗逆转录病毒治疗可以独立诱导HIV相关的神经性疼痛（HIV-NP）。缺乏可以缓解HIV-NP的药物或治疗方式。据报道，烟熏大麻可改善神经性疼痛患者的疼痛措施。大麻,植物大麻素，和内源性大麻素，例如N-花生四酰基乙醇胺（anandamide;AEA）和2-花生四酰基甘油（2-AG），通过大麻素受体（CBRs）产生一些作用。内源性大麻素被各种酶如脂肪酸酰胺水解酶(FAAH)和单酰基甘油脂肪酶降解。我们搜索了PubMed,谷歌学者，临床试验。gov和临床试验注册。欧盟在研究HIV-NP和大麻的已发表论文中使用各种关键词及其组合，大麻素,或内源性大麻素，截至2020年12月27日。包括评估调节内源性大麻素系统（ECS）的分子在HIV-NP动物模型和HIV-NP患者中预防和/或治疗疼痛的功效的所有原始研究文章。PubMed搜索共产生117篇文章，而谷歌学者搜索总共产生了9467篇文章。在满足纳入标准的13篇文章中，有11篇文章在两次搜索中都找到，而2篇文章仅在GoogleScholar中找到。临床试验和临床试验注册。欧盟搜索产生了五项注册试验，其中三项已完成并有结果。十项临床前研究发现，内源性大麻素（2-AG和AEA），合成混合CB1R/CB2R激动剂WIN55,212-2，一种CB2R选择性植物大麻素β-石竹烯，合成的CB2R选择性激动剂（AM1710，JWH015，JWH133和Gp1a，但不是HU308)；FAAH抑制剂(棕榈酰烯丙基酰胺，URB597和PF-3845）和吲哚美辛加米诺环素的药物组合，以依赖CBR的方式产生其效果，预防和/或减毒已建立的HIV-NP的发展。两项临床试验表明，与安慰剂相比，烟熏大麻在缓解HIV-NP方面的功效更高，而另一项临床试验表明大麻素，一种不激活CBR的大麻素，没有减少HIV-NP。现有的临床前结果表明，针对ECS预防和治疗HIV-NP是一种合理的治疗选择。临床证据表明，吸食大麻可缓解HIV-NP。需要进一步的研究来确定针对ECS并通过吸烟以外的其他途径提供的非精神活性药物是否可以用作HIV-NP的治疗选择。
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