Preliminary data on the potential for unintentional antidoping rule violations by permitted cannabidiol (CBD) use,Drug Testing and Analysis

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Preliminary data on the potential for unintentional antidoping rule violations by permitted cannabidiol (CBD) use
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2020-10-30 , DOI: 10.1002/dta.2959
Ute Mareck ₁ , Gregor Fusshöller ₁ , Hans Geyer ₁ , Marilyn A Huestis ₂ , Anja B Scheiff ₃ , Mario Thevis ₁

Affiliation

According to the World Anti‐Doping Agency (WADA) regulations, cannabinoids use is prohibited in competition except for cannabidiol (CBD) use. For an adverse analytical finding (AAF) in doping control, cannabinoid misuse is based on identification of the pharmacologically inactive metabolite 11‐nor‐delta‐9‐carboxy‐tetrahydrocannabinol‐9‐carboxylic acid (carboxy‐THC) in urine at a concentration greater than 180 ng/ml. All other (minor) cannabinoids are reported as AAF when identified, except for CBD that has been explicitly excluded from the class of cannabinoids on WADA's Prohibited List since 2018. However, due to the fact that CBD isolated from cannabis plants may contain additional minor cannabinoids, the permissible use of CBD can lead to unintentional violations of antidoping regulations. An assay for the detection of 16 cannabinoids in human urine was established. The sample preparation consisted of enzymatic hydrolysis of glucuronide conjugates, liquid–liquid extraction, trimethylsilylation, and analysis by gas chromatography/tandem mass spectrometry (GC–MS/MS). Spot urine samples from CBD users, as well as specimens obtained from CBD administration studies conducted with 15 commercially available CBD products, were analyzed, and assay characteristics such as selectivity, reproducibility of detection at the minimum required performance level, limit of detection, and limit of identification were determined. An ethical committee approved controlled single dose commercially available CBD products administration study was conducted to identify 16 cannabinoids in urine samples collected after ingestion or application of the CBD products as well as their presence in spot urine samples of habitual CBD users. Variable patterns of cannabinoids or their metabolites were observed in the urine samples, especially when full spectrum CBD products were consumed. The presence of minor cannabinoids or their metabolites in an athlete's in‐competition urine sample represents a substantial risk of an antidoping rule violation.

中文翻译：

关于允许使用大麻二酚 (CBD) 无意违反反兴奋剂规则的可能性的初步数据

根据世界反兴奋剂机构 (WADA) 的规定，除使用大麻二酚 (CBD) 外，比赛中禁止使用大麻素。对于兴奋剂控制中的不利分析发现 (AAF)，大麻素滥用是基于鉴定尿液中的药理学上无活性代谢物 11-nor-delta-9-carboxy-tetrahydrocannabinol-9-carboxy (carboxy-THC)，浓度更高超过 180 纳克/毫升。所有其他（次要）大麻素在识别时均报告为 AAF，但自 2018 年以来已被明确排除在 WADA 禁用清单上的大麻素类别之外的 CBD 除外。然而，由于从大麻植物中分离出的 CBD 可能含有额外的次要大麻素，允许使用 CBD 可能导致无意违反反兴奋剂规定。建立了检测人尿中 16 种大麻素的检测方法。样品制备包括葡萄糖醛酸结合物的酶水解、液-液萃取、三甲基硅烷化和气相色谱/串联质谱 (GC-MS/MS) 分析。对来自 CBD 用户的现场尿液样本以及从 15 种商用 CBD 产品进行的 CBD 管理研究中获得的样本进行了分析，并分析了检测特性，例如选择性、最低要求性能水平下的检测重现性、检测限和限制鉴定的确定。进行了一项伦理委员会批准的受控单剂量市售 CBD 产品管理研究，以确定摄入或应用 CBD 产品后收集的尿液样本中的 16 种大麻素，以及它们在习惯性 CBD 用户的现场尿液样本中的存在。在尿液样本中观察到大麻素或其代谢物的不同模式，尤其是在食用全谱 CBD 产品时。运动员赛中尿液样本中含有少量大麻素或其代谢物，这代表了违反反兴奋剂规则的重大风险。

更新日期：2020-10-30

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