Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Department of Pharmacy Services, Corewell Health William Beaumont University Hospital, Royal Oak, Michigan, USA.
Pharmacotherapy. 2023 Dec;43(12):1327-1338. doi: 10.1002/phar.2881. Epub 2023 Oct 11.
This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords. The major outcome was hemorrhage or thrombosis and if available the relative change in quantitative intensity of anticoagulation after cannabinoid exposure. The search generated 959 citations. After the removal of 440 duplicates, 519 citations were screened. Overall, with the exception of warfarin, evidence supporting an interaction between cannabinoids and anticoagulants is non-existent. Seven case reports evaluating an interaction with warfarin were reported. Cannabis doses involved were either extremely high (e.g., >260 mg/day of delta-9-tetrahydrocannabidiol [THC] or >600 mg/day of cannabidiol [CBD]) or were not known. Hemorrhage was identified in 14.2% (1/7) of reports and thrombosis in 0%. Quantitative anticoagulation levels were increased in patients on warfarin (elevated International Normalized Ratio [INR]) in six of seven cases. A maximum INR change was available in five of seven reports, ranging from +0.4 to +9.61. One report found no change in INR after 4 days of medical cannabis exposure. Another report outlined two separate episodes of INR elevation associated with bleeding requiring hospitalization and reversal after marijuana smoking. Four cases involved reduction in weekly warfarin dose ranging from 22% to 31%. The Drug Information Probability Score was calculated in six cases, with a score of probable for five cases and possible for one. Very low-quality data support a potential drug-drug interaction with warfarin and both THC and CBD. Clinician recognition of this potential interaction is important. Available evidence supports the need to conduct a drug interaction study between cannabinoids and warfarin to clarify the existence of an interaction.
本系统评价评估了大麻类物质存在时抗凝剂效果可能发生改变的程度。检索了以下数据库：EMBASE、PubMed、Web of Science、Scopus、PscycINFO 和 CINAHL，检索时间从数据库建立至 2023 年 5 月。检索词包括大麻和抗凝剂以及药物相互作用和相关关键词。主要结局是出血或血栓形成，以及在接触大麻素后抗凝强度的定量变化是否可用。搜索生成了 959 条引文。去除 440 条重复引文后，筛选了 519 条引文。总体而言，除华法林外，尚无证据支持大麻类物质与抗凝剂之间存在相互作用。报告了 7 例评估与华法林相互作用的病例报告。涉及的大麻剂量要么极高（例如，每天>260 毫克的 delta-9-四氢大麻酚[THC]或每天>600 毫克的大麻二酚[CBD]），要么未知。在 7 例报告中，有 14.2%（1/7）的报告中出现出血，0%的报告中出现血栓形成。在接受华法林治疗的患者中，有 6 例（7 例中的 6 例）患者的定量抗凝水平升高（国际标准化比值[INR]升高）。在 7 例报告中的 5 例中，可获得最大 INR 变化，范围从+0.4 到+9.61。有 1 例报告在接受医用大麻暴露 4 天后，INR 无变化。另一例报告概述了与吸烟大麻相关的两次 INR 升高的单独发作，需要住院治疗和逆转。有 4 例病例需要减少每周华法林剂量，范围从 22%到 31%。在 6 例病例中计算了药物信息概率评分，其中 5 例为可能，1 例为不太可能。极低质量的数据支持与华法林和 THC 和 CBD 都存在潜在的药物-药物相互作用。临床医生认识到这种潜在的相互作用很重要。现有证据支持有必要进行大麻类物质与华法林之间的药物相互作用研究，以阐明相互作用的存在。
