A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History.
A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History.
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DOI：
10.1089/can.2021.0176
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发表时间：
2022-12
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
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作者：
四氢大麻酚（Δ9-THC）和大麻二酚（CBD）的口服给药途径消除了吸烟的有害影响，并有可能为治疗和娱乐应用提供有效的大麻。我们研究了CBD、Δ9-THC、11-OH-THC和11-去甲-9-羧基-Δ9-THC（THC-COOH）在一种新型口服给药系统Solutech™中的药代动力学，并与健康人群中的中链大麻素稀释的大麻油（MCT-油）进行了比较。32名受试者被随机分为两个研究组，采用比较对照，平行研究设计。为了评估Δ9-THC、CBD、11-OH-THC和THC-COOH的药代动力学，在单次剂量的Solutech后在给药前（t=0）和给药后10、20、30和45分钟以及1、1.5、2、2.5、3、4、5、6、8、12、24和48小时收集血液Omg Δ9-THC，9.76mg CBD）或MCT（10.Omg Δ9-THC，9.92mg CBD）。在0.5、1、2、4、6、8、12、24和48 h测量心率和血压。研究大麻使用史、体重指数、性别和药代动力学参数之间的关系。在急性给药前和给药后48小时评估安全性。与MCT油相比，Solutech的急性消耗提供了显著更大的最大浓度（Cmax）、更大的消除和吸收速率常数、更快的达到Cmax的时间和滞后时间以及所有分析物的半衰期（p<0.001）。此外，大麻使用史对CBD、Δ9-THC、11-OH-THC和THC-COOH的药代动力学参数有显著影响。平均而言，与首次使用年龄较早的参与者相比，首次使用年龄较晚的参与者具有较高的Δ9-THC，CBD和THC-COOH Cmax以及Δ9-THC，CBD，THC-COOH和11-OH-THC的Cmax和半衰期较晚（p≤0.032）。那些使用娱乐性大麻多年的人的Δ9-THC和CBD的曲线下面积更高，CBD的Cmax和11-OH-THC的半衰期比那些使用较少的人更长（p≤0.048）。本研究表明，与MCT油相比，Solutech的消耗增强了测量的大多数药代动力学参数。参与者的大麻使用史，包括首次使用的年龄和使用大麻的年数，显著影响了研究的药代动力学参数。两种产品的急性消费被认为是安全的，耐受性良好。结果表明，Solutech可以优化大麻制剂的生物利用度。
An oral route of administration for tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) eliminates the harmful effects of smoking and has potential for efficacious cannabis delivery for therapeutic and recreational applications. We investigated the pharmacokinetics of CBD, Δ9-THC, 11-OH-THC, and 11-nor-9-carboxy-Δ9-THC (THC-COOH) in a novel oral delivery system, Solutech™, compared to medium-chain triglyceride-diluted cannabis oil (MCT-oil) in a healthy population. Thirty-two participants were randomized and divided into two study arms employing a comparator-controlled, parallel-study design. To evaluate the pharmacokinetics of Δ9-THC, CBD, 11-OH-THC, and THC-COOH, blood was collected at pre-dose (t=0) and 10, 20, 30, and 45, min and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48 h post-dose after a single dose of Solutech (10.0 mg Δ9-THC, 9.76 mg CBD) or MCT (10.0 mg Δ9-THC, 9.92 mg CBD). Heart rate and blood pressure were measured at 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h. Relationships between cannabis use history, body mass index, sex, and pharmacokinetic parameters were investigated. Safety was assessed before and at 48 h post-acute dose. Acute consumption of Solutech provided a significantly greater maximum concentration (Cmax), larger elimination and absorption rate constants, faster time to Cmax and lag time, and half-life for all analytes compared to MCT-oil (p<0.001). In addition, cannabis use history had a significant influence on the pharmacokinetic parameters of CBD, Δ9-THC, 11-OH-THC, and THC-COOH. On average, participants with later age of first use had higher Δ9-THC, CBD, and THC-COOH Cmax and later time-to-Cmax and half-life for Δ9-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032). Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and longer 11-OH-THC half-life than those with less (p≤0.048). This study demonstrated that consumption of Solutech enhanced most pharmacokinetics parameters measured compared to MCT-oil. Participant's cannabis use history, including their age of first use and number of years using cannabis significantly impacted pharmacokinetic parameters investigated. Acute consumption of both products was found to be safe and well tolerated. The results suggest that Solutech may optimize bioavailability from cannabis formulations.
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DOI：
10.1016/j.pbb.2016.01.007
发表时间：
2017-01
期刊：
Pharmacology, biochemistry, and behavior
影响因子：
--
作者：
Fogel JS;Kelly TH;Westgate PM;Lile JA
通讯作者：
Lile JA
DOI：
10.3390/ph13090219
发表时间：
2020-08-28
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Millar SA;Maguire RF;Yates AS;O'Sullivan SE
通讯作者：
O'Sullivan SE
影响因子：
3.8
作者：
Atsmon, Jacob;Cherniakov, Irina;Sacks, Hagit
通讯作者：
Sacks, Hagit
影响因子：
2.7
作者：
Eichler, Martin;Spinedi, Luca;Drewe, Juergen
通讯作者：
Drewe, Juergen
影响因子：
3.7
作者：
Bosnyak D;McDonald AC;Gasperin Haaz I;Qi W;Crowley DC;Guthrie N;Evans M
通讯作者：
Evans M