Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.
Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.
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DOI：
10.1097/ftd.0b013e3182a5c446
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发表时间：
2014-04
影响因子：
2.5
通讯作者：
Huestis MA
中科院分区：
文献类型：
--
作者：
Milman G;Bergamaschi MM;Lee D;Mendu DR;Barnes AJ;Vandrey R;Huestis MA
最近，大剂量口服合成三角洲-9-四氢大麻酚(THC)被证明可以缓解大麻的戒断症状。目前的数据描述了接受大剂量口服THC药物治疗和后来接受吸食大麻挑战的慢性每日大麻吸烟者的大麻素药代动力学。11名每日吸食大麻的人每天接受0、30、60或120毫克/天的THC，共四次为期5天的服药疗程，每一次以9天的临时大麻吸食为间隔。在第5天，参与者被要求抽一支5.9%的THC香烟。分别于第1天和第5天采集血浆，用GC-GC-MS法定量检测THC、11-羟基-THC(11-OH-THC)和11-Nor-9-Carxy-THC(THCCOOH)。THC、11-OH-THC和0.5-200 THCCOOH的线性范围分别为0.5-100、1-50和0.5-200。在安慰剂剂量期间，THC、11-OH-THC和THCCOOH浓度持续下降，而所有大麻素在有效给药期间均呈剂量依赖性增加。THC随时间的增加在任何剂量后均不显著，11-OH-THC在60 mg/d和120 mg/d剂量下显著增加，THCCOOH仅在120 mg/d剂量下显著增加。THC、11-OH-THC和THCCOOH浓度在吸食大麻后0.25h内达到峰值，但在吸食大麻前0.5h，THC浓度在120 mg/d后达到峰值。服用安慰剂时注意到的显著戒断效应得到了血浆THC和11-OH-THC浓度显著下降的支持。在主动给药期间，THC和11-OH-THC浓度的显著增加支持戒断症状的抑制。吸食大麻后的THC浓度只能与口服THC剂量区分1小时，太短了，无法有效地识别大麻复发。THCCOOH/THC比值在口服Dronabinol戒断后14小时较高，但不能区分口服THC剂量和吸食大麻。
Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic daily cannabis smokers who received high-dose oral THC pharmacotherapy and later, a smoked cannabis challenge. 11 daily cannabis smokers received 0, 30, 60, or 120 mg/day THC for four 5-day medication sessions, each separated by 9-days of ad-libitum cannabis smoking. On the 5th day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the 1st and 5th days was quantified by GC-GC-MS for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5–100 for THC, 1–50 11-OH-THC, and 0.5–200 THCCOOH. During placebo dosing, THC, 11-OH-THC and THCCOOH concentrations consistently decreased, while all cannabinoids increased dose-dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during 60 and 120 mg/day doses, and THCCOOH increased significantly only during the 120 mg/day dose. THC and 11-OH-THC, and THCCOOH concentrations peaked within 0.25 h after cannabis smoking, except after 120 mg/day THC when THCCOOH peaked 0.5 h before smoking. The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 h, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 h after overnight oral dronabinol abstinence, but cannot distinguish oral THC dosing from smoked cannabis intake.