Perkins Daniel, Butler Juliet, Ong Katherine, Nguyen Tri-Hung, Cox Susan, Francis Barbara, Mcintosh Michelle, Lilley Brian
Department of Health and Human Services, Office of Medicinal Cannabis, 50 Lonsdale St, Melbourne, VIC, 3000, Australia.
University of Melbourne, Parkville, VIC, Australia.
Eur J Drug Metab Pharmacokinet. 2020 Oct;45(5):575-586. doi: 10.1007/s13318-020-00624-6.
There is increasing interest in the use of purified cannabidiol (CBD) as a treatment for a wide range of conditions due to its reported anti-inflammatory, anxiolytic, antiemetic and anticonvulsant properties.
The objective of this study was to assess the safety, tolerability and pharmacokinetics of a single ascending dose of a new lipid-based oral formulation of CBD in healthy volunteers after a high-fat meal.
A total of 24 eligible healthy volunteers (aged 18-48 years) were randomised to one of three sequential cohorts (each with six active and two placebo subjects). Cohort 1 received 5 mg/kg CBD or placebo, cohort 2 received 10 mg/kg CBD or placebo (cohort 2), and cohort 3 received 20 mg/kg CBD or placebo. Data relating to adverse events, vital signs, clinical laboratory assessments, 12-lead ECGs, physical examinations and concomitant medications were collected to assess safety and tolerability. Blood samples were collected up to 8 days postdose and plasma was analysed by liquid chromatography and mass spectrometry to assess the pharmacokinetics of the CBD formulation.
CBD was well tolerated in the healthy volunteers (mean age: 24.0 years) treated with a single oral dose of CBD. There were no safety concerns with increasing the dose and the safety profiles of the CBD-treated and placebo-treated subjects were similar. The most frequently reported treatment emergent adverse events (TEAEs) were headache (17%) and diarrhoea (8%). There were no reported serious adverse events (SAEs) and no clinical laboratory findings, vital signs, ECGs or physical examination findings that were reported as TEAEs or were of clinical significance during the study. After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (T) was 4 h across all three CBD dose cohorts. The CBD plasma exposure [maximum observed plasma concentration (C) and the area under the concentration-time curve (AUC)] increased in a dose-proportional manner and declined to levels approaching the lower level of quantification by day 8. The terminal elimination half-life was approximately 70 h, suggesting that 2-3 weeks are needed to fully eliminate CBD.
This new CBD formulation demonstrated a favourable safety and tolerability profile in healthy volunteers that was consistent with the profiles reported for other purified CBD products. No severe or serious AEs were observed in this study and there were no safety concerns.
ACTRN12618001424291. Registered August 2018.
由于纯化的大麻二酚（CBD）具有抗炎、抗焦虑、止吐和抗惊厥特性，其在多种病症治疗中的应用正受到越来越多的关注。
本研究的目的是评估在高脂餐后，健康志愿者单次递增剂量服用新型脂质基口服CBD制剂的安全性、耐受性和药代动力学。
总共24名符合条件的健康志愿者（年龄18 - 48岁）被随机分为三个连续队列之一（每个队列有6名活性药物受试者和2名安慰剂受试者）。队列1接受5mg/kg CBD或安慰剂，队列2接受10mg/kg CBD或安慰剂，队列3接受20mg/kg CBD或安慰剂。收集与不良事件、生命体征、临床实验室评估、12导联心电图、体格检查和伴随用药相关的数据，以评估安全性和耐受性。给药后长达8天采集血样，通过液相色谱和质谱分析血浆，以评估CBD制剂的药代动力学。
单次口服CBD治疗的健康志愿者（平均年龄：24.0岁）对CBD耐受性良好。增加剂量不存在安全性问题，CBD治疗组和安慰剂治疗组的安全性特征相似。最常报告的治疗中出现的不良事件（TEAE）是头痛（17%）和腹泻（8%）。未报告严重不良事件（SAE），且在研究期间，未将任何临床实验室检查结果、生命体征、心电图或体格检查结果报告为TEAE或具有临床意义。高脂餐后，给药后15分钟在血浆样本中检测到CBD；所有三个CBD剂量队列的血浆浓度达峰中位时间（T）为4小时。CBD的血浆暴露量[最大观察血浆浓度（C）和浓度 - 时间曲线下面积（AUC）]呈剂量比例增加，并在第8天降至接近定量下限的水平。终末消除半衰期约为70小时，表明完全消除CBD需要2 - 3周。
这种新型CBD制剂在健康志愿者中显示出良好的安全性和耐受性，与其他纯化CBD产品报告的特征一致。本研究未观察到严重或重度不良事件，不存在安全性问题。
ACTRN12618001424291。2018年8月注册。
