Critical Review Report: 5F-MDMB-PICA.
Critical Review Report: 5F-MDMB-PICA.
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批判性审查报告：5F-MDMB-PICA。
DOI：
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
S. Brandt
中科院分区：
文献类型：
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作者：
S. Brandt
物质鉴定：2016 年首次描述了 5F-MDMB-PICA (5F-MDMB-2201)（IUPAC 名称：甲基 (2S)-2-{[1-(5-氟戊基)-1H-吲哚-3-羰基]氨基}-3,3-二甲基丁酸酯）的鉴定。从缉获和收集中获得的信息表明，它以粉末形式存在，并作为草本植物中的合成成分最常用于吸烟和/或电子烟目的的混合物。它是 5F-ADB (5F-MDMB-PINACA) 的吲哚类似物，被列入 1971 年《精神药物公约》附表 II。 WHO 审查历史：5F-MDMB-PICA 之前尚未经过预审查或严格审查。化学：没有关于在毒品市场上流通的查获的 5FMDMB-PICA 产品所采用的合成路线的具体信息，但存在直接的制备方法，无需获取国际管制的前体。不对称碳原子的存在产生 (R)- 和 (S)- 对映体，并且 5F-MDMB-PICA 似乎最常作为 (S)- 对映体使用。易于转化为受控物质：没有可用的具体信息，但 5F-MDMB-PICA 似乎不太可能转化为任何国际药物公约中目前列出的物质。与已知物质的相似性/对中枢神经系统的影响：目前可获得的信息表明 5F-MDMB-PICA 具有合成大麻素受体激动剂 (SCRA) 的功能。目前尚无有关体内诱导效应的信息，但现有数据表明 5F-MDMB-PICA 可能会表现出与国际控制的其他 SCRA（大麻素受体的有效完全激动剂）（例如 5F-ADB）相同的特征。一般药理学：5F-MDMB-PICA 以其纯品形式存在，但主要作为添加到植物基质中的合成成分，主要用于吸食（或吸食），但无法获得有关剂量的可靠数据。目前有少量体外研究，数据表明 5F-MDMB-PICA 在低纳摩尔浓度下结合并激活人类 CB1 和 CB2 受体。 5F-MDMB-PICA 作为两种受体亚型的完全激动剂，其效力显着高于 Δ9-THC，这一点在 1971 年《精神药物公约》中列出的其他 SCRA 中也观察到。从体外代谢研究和生物样本检测中收集的数据表明，观察到的生物转化包括单羟基化、氧化脱氟、脱氢、酰胺和酯水解及其组合。还检测到葡萄糖醛酸化产物。毒理学：无法识别信息。人类不良反应：尚无与服用 5F-MDMBPICA 相关的临床特征的详细信息。然而，康涅狄格州（美利坚合众国）描述了与检测到 5F-MDMB-PICA 和其他 SCRA 和芬太尼有关的“大规模用药过量”病例。报告的临床特征包括精神状态下降、烦躁性谵妄和癫痫发作。在 2018 年 9 月的 6 天内，美国华盛顿特区发现了 244 起用药过量病例（详细信息未报告），其中还检测到了 5F-ADB 和其他 SCRA。从其他 SCRA 中毒病例中收集的数据表明，临床特征可能包括对胃肠道、神经系统和心血管系统的一系列不良影响。潜在依赖性：没有在人类或动物身上进行的研究可以确定。滥用可能性：无法确定与 5F-MDMB-PICA 特别相关的研究。治疗应用/用途： 5F-MDMB-PICA 尚不清楚有任何治疗用途。列入世界卫生组织基本药物标准清单：5F-MDMB-PICA 未列入。营销授权：据了解 5F-MDMB-PICA 没有任何营销授权。工业用途：5F-MDMB-PICA 尚无任何农业、工业或化妆品用途。非医疗用途：使用方式可能涉及（有意或无意）其他药物的组合使用，并且使用者可能不知道摄入的确切剂量或化合物（通过任何途径）。无法确定专门调查 5F-MDMBPICA 患病率的家庭或亚人群调查。使用 SCRA 的人一般包括娱乐使用者、高风险物质使用者，但也包括接受药物测试的人，例如接受戒毒治疗的人、囚犯、戒毒控制计划人员和司机。公共卫生问题的性质和严重程度：以草药吸烟混合物形式出售的产品的药物成分和数量经常发生变化，而且产品标签上往往没有说明，这导致将公共健康危害与特定药物（如 5F-MDMB-PICA）明确关联起来面临挑战。使用这些药物的人很可能不知道其成分和数量。这些产品的消费可能对各种使用者都有吸引力，例如大麻的经常使用者和那些相信 SCRA 的使用可能有助于避免药物测试程序中出现阳性结果的人。有迹象表明，社会弱势群体和受到污名化的物质使用者（例如无家可归者和监狱人口）越来越多地与 SCRA 产品的问题使用联系在一起。大量使用 SCRA 与有问题的戒断症状有关，需要进一步研究来评估潜在机制。合法生产、消费和国际贸易：5F-MDMB-PICA 可作为标准参考材料，由许多商业供应商生产用于科学研究。无法确定其他用途。非法制造和流通：5F-MDMB-PICA 于 2016 年底开始在欧洲和美国出现。一般来说，SCRA 通常以纯品形式进口，并在国内转化为草药形式。近年来，有报道称 SCRA 以浸渍纸（例如信件）和纺织品的形式走私到监狱，这也延伸到了 5F-MDMBPICA 的检测。目前的国际管制及其影响：5F-MDMB-PICA 不受 1961 年、1971 年或 1988 年联合国公约的管制。当前和过去的国家管制：5F-MDMB-PICA 在一些联合国成员国受到管制。
Substance identification: The identification of 5F-MDMB-PICA (5F-MDMB-2201) (IUPAC name: methyl (2S)-2-{[1-(5-fluoropentyl)-1H-indole-3-carbonyl]amino}-3,3-dimethylbutanoate) has been described first in 2016. Information obtained from seizures and collections suggests that it has been encountered in powdered form and as a synthetic constituent in herbal plant mixtures most commonly distributed for the purpose of smoking and/or vaping. It is the indole analogue of 5F-ADB (5F-MDMB-PINACA) that is listed in Schedule II of the Convention on Psychotropic Substances of 1971. WHO Review History: 5F-MDMB-PICA has not been previously pre-reviewed or critically reviewed. Chemistry: There is no specific information available about the routes of synthesis employed for seized 5FMDMB-PICA products circulating on the drug market but straightforward methods for its preparation exist without requiring access to precursors that are controlled internationally. The presence of an asymmetric carbon atom gives rise to the (R)- and (S)-enantiomer and it seems likely for 5F-MDMB-PICA to be most commonly available as the (S)-enantiomer. Ease of convertibility into controlled substances: There is no specific information available but it appears unlikely that 5F-MDMB-PICA is converted into a substance currently listed in any of the international drug conventions. Similarity to known substances / Effects on the central nervous system: The information currently available suggests that 5F-MDMB-PICA functions as a synthetic cannabinoid receptor agonist (SCRA). Information about effects induced in vivo is currently not available but the existing data suggest that 5F-MDMB-PICA will likely exhibit a profile shared by other SCRAs controlled internationally (potent full agonists at cannabinoid receptors) such as 5F-ADB. General pharmacology: 5F-MDMB-PICA, in its pure form but mostly as a synthetic constituent added to a plant matrix, is primarily smoked (or vaped) although reliable data about dosage are unavailable. A small number of in vitro studies are currently available and the data indicate that 5F-MDMB-PICA binds to and activates human CB1 and CB2 receptors at low nanomolar concentrations. 5F-MDMB-PICA acted as a full agonist at both receptor subtypes with significantly higher potency than Δ9-THC which has also been observed with other SCRAs that are listed in the Convention on Psychotropic Substances of 1971. Data collected from in vitro metabolism studies and detections in biological specimens revealed that the biotransformation observed included mono-hydroxylation, oxidative defluorination, dehydrogenation, amide, and ester hydrolysis, as well as combinations thereof. Glucuronidation products have also been detected. Toxicology: Information could not be identified. Adverse reactions in humans: Detailed information about the clinical features associated with the consumption of 5F-MDMBPICA specifically is not available. However, “mass-overdose” cases were described in Connecticut (United States of America (USA)) that have been associated with the detection of 5F-MDMB-PICA and other SCRAs and fentanyl. Clinical features reported included decreased mental status, agitated delirium, and seizures. Within a 6-day period in September 2018, 244 overdose cases (details not reported) have been identified in Washington, DC, (USA) that also included the detection of 5F-ADB and other SCRAs. Data collected from intoxication cases with other SCRAs suggest that clinical features might include a range of adverse effects on gastrointestinal, neurological, and cardiovascular systems. Dependence potential: No studies carried out in humans or animals could be identified. Abuse potential: Studies specifically linked to 5F-MDMB-PICA could not be identified. Therapeutic applications / usefulness: 5F-MDMB-PICA is not known to have any therapeutic uses. Listing on WHO Model List of Essential Medicines: 5F-MDMB-PICA is not listed. Marketing authorizations: 5F-MDMB-PICA is not known to have any marketing authorisations. Industrial use: 5F-MDMB-PICA is not known to have any agricultural, industrial or cosmetic uses. Non-medical use: The mode of use may involve the combinational use (intentionally or unintentionally) of other drugs and users may be unaware of the exact dose or compound being ingested (by whatever route). Household or subpopulation surveys that specifically probe for prevalence of 5F-MDMBPICA could not be identified. People who use SCRAs in general include recreational users, high-risk substance users but also individuals who are subject to drug testing such as people in drug treatment, prisoners, abstinence control programs and drivers. Nature and magnitude of public health problems: Products sold as herbal smoking mixtures frequently change in drug composition and quantity, often without indications on product labels, which results in challenges to unambiguously correlate harms to public health with a specific drug such as 5F-MDMB-PICA. People who use these drugs are most likely not aware of the identity of the constituent and the quantity. The consumption of these products might be attractive to a variety of users, such as regular users of cannabis and those who believe that SCRA use might help with avoiding a positive finding in drug testing procedures. There are indications that socially vulnerable and stigmatised substance users, for example found in homeless and prison populations, are increasingly associated with problematic use of SCRA products. Heavy use of SCRAs has been associated with problematic withdrawal symptoms and further research is needed to evaluate the underlying mechanisms. Licit production, consumption, and international trade: 5F-MDMB-PICA is available as standard reference material and produced for scientific research by a number of commercial suppliers. Other uses could not be identified. Illicit manufacture and traffic: 5F-MDMB-PICA began to emerge at the end 2016 both in Europe and the USA. In general, SCRAs are often imported in their pure form and converted into herbal forms on the domestic level. In recent years it has emerged that SCRAs have been smuggled into prisons in the form of impregnated papers (e.g. letters) and textiles and this extended to the detection of 5F-MDMBPICA. Current international controls and their impact: 5F-MDMB-PICA is not controlled under the 1961, 1971 or 1988 United Nations Conventions. Current and past national controls: 5F-MDMB-PICA is controlled in some UN Member States.
影响因子：
2.9
作者：
Mogler, Lukas;Franz, Florian;Auwaerter, Volker
通讯作者：
Auwaerter, Volker