Urinary cannabinoid levels during nabiximols (Sativex®)-medicated inpatient cannabis withdrawal
Urinary cannabinoid levels during nabiximols (Sativex®)-medicated inpatient cannabis withdrawal
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DOI：
10.1007/s11419-016-0330-0
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发表时间：
2017-01-01
影响因子：
2.2
通讯作者：
McGregor, Iain S.
中科院分区：
文献类型：
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作者：
Kevin, Richard C.;Allsop, David J.;McGregor, Iain S.
Nabiximols（Sativex（A（R）））是一种含有匕首（9）-四氢大麻酚（THC）和大麻二酚（CBD）的口腔喷雾剂。它已显示出作为治疗大麻戒断和依赖的激动剂替代疗法的前景。在治疗期间监测尿大麻素水平对于确定大麻素药代动力学和临床试验期间的治疗依从性非常重要。在这里，我们使用最近描述的水解方法从其葡糖苷酸缀合物中释放尿CBD，并描述了大麻戒断期间接受那比昔莫治疗（或安慰剂）的患者的尿CBD，THC，11-去甲-9-羧基-THC（THC-COOH）和11-羟基-THC（11-OH-THC）的轨迹。在6天住院治疗方案之前和期间以及3天无药物洗脱期间采集尿液和血浆样本。用红鲍鱼β-葡萄糖醛酸酶水解尿液，并使用液相色谱-串联质谱法定量每日尿液中的CBD、THC、THC-COOH和11-OH-THC。总体而言，尿液和血浆大麻素水平遵循相似的轨迹，并密切反映了给药方案。在那比西莫治疗期间，尿液和血浆中的CBD水平显著上升，而THC及其代谢物的浓度保持在或略高于治疗前水平。水解后，检测到尿CBD的水平分别为非水解血浆和非水解尿液的50倍和200倍。THC、THC-COOH和11-OH-THC浓度也通过尿水解放大。这种方法可以敏感地评估尿CBD，并可能在涉及nabiximols或其他大麻素疗法的临床研究中证明是有用的。
Nabiximols (Sativex(A (R))) is a buccal spray containing both a dagger(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). It has shown promise as an agonist substitution therapy for treating cannabis withdrawal and dependence. Monitoring urinary cannabinoid levels during treatment is important for determination of cannabinoid pharmacokinetics and for treatment adherence during clinical trials. Here, we use a recently described hydrolysis method to liberate urinary CBD from its glucuronide conjugate, and describe the trajectory of urinary CBD, THC, 11-nor-9-carboxy-THC (THC-COOH), and 11-hydroxy-THC (11-OH-THC) in patients receiving nabiximols treatment (or placebo) during cannabis withdrawal. Urine and plasma samples were taken before and during a 6-day inpatient treatment regime and during a 3-day drug-free washout. Urine was hydrolysed with red abalone beta-glucuronidase, and CBD, THC, THC-COOH, and 11-OH-THC were quantified in daily urine using liquid chromatography-tandem mass spectrometry. Overall, urine and plasma cannabinoid levels followed similar trajectories and closely reflected the dosing schedule. During nabiximols treatment, CBD levels in urine and plasma rose markedly, while concentrations of THC and its metabolites remained at, or slightly above, pre-treatment levels. Following hydrolysis, urinary CBD was detected at levels 50 and 200 times as high as those in non-hydrolysed plasma and non-hydrolysed urine, respectively. THC, THC-COOH, and 11-OH-THC concentrations were also amplified by urinary hydrolysis. This method allows sensitive assessment of urinary CBD, and may prove useful in clinical studies involving nabiximols or other cannabinoid therapies.