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一项在健康成年人中比较汽化δ-8-四氢大麻酚和δ-9-四氢大麻酚急性效应的受试者内交叉试验。

A within-subject cross-over trial comparing the acute effects of vaporized delta-8-tetrahydrocannabinol and delta-9-tetrahydrocannabinol in healthy adults.

作者信息

Spindle Tory R, Zamarripa C Austin, Schriefer Destiny, Cone Edward J, Winecker Ruth, Flegel Ronald, Hayes Eugene, Davis Lisa S, Kuntz David, Vandrey Ryan

机构信息

Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, USA.

Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, USA.

出版信息

Drug Alcohol Depend. 2025 Jul 1;272:112684. doi: 10.1016/j.drugalcdep.2025.112684. Epub 2025 Apr 21.

Abstract

BACKGROUND

The prevalence and accessibility of Δ8-tetrahydrocannabinol (Δ8-THC), a chemical isomer of Δ9-tetrahydrocannabinol (Δ9-THC), has increased drastically, yet no controlled studies have directly compared the effects of vaporized Δ8-THC and Δ9-THC .

METHODS

Twenty healthy adults with no past-month cannabis exposure completed five randomized outpatient sessions in a within-subjects, double-blind, crossover design. Participants inhaled Δ8-THC (10, 20, 40mg), Δ9-THC (20mg), or placebo (distilled water) using the Mighty Medic vaporizer. Measures included subjective drug effects, cognitive/psychomotor performance, puff topography, vital signs, and whole blood concentrations of Δ8-THC, Δ9-THC, and their metabolites.

RESULTS

All Δ8-THC doses and Δ9-THC produced subjective drug effects that differed from placebo. 20mg Δ9-THC elicited stronger ratings of "drug effect" and "unpleasant" than 10mg Δ8-THC; no other subjective effects differed between Δ8-THC and Δ9-THC. 20mg Δ9-THC impaired DRUID performance compared with placebo; no other significant differences were observed between conditions on cognitive/psychomotor measures. Few pharmacodynamic differences were observed between Δ8-THC doses. Evidence of compensatory puffing emerged, with longer/larger puffs at lower Δ8-THC doses and placebo. Blood cannabinoid concentrations revealed that Δ8-THC metabolism differed from Δ9-THC, with less psychoactive 11-OH metabolite formed after Δ8-THC exposure.

CONCLUSION

Various doses of vaporized Δ8-THC elicited comparable psychoactive effects as vaporized Δ9-THC, which is noteworthy considering Δ8-THC is less potent and generally perceived as less harmful/intoxicating than Δ9-THC. The magnitude of effects from cannabinoids is dictated by several factors including dose, route of administration, and, for inhaled methods, puffing behaviors. These data should be considered in future drug policy and public education initiatives.

摘要

背景

Δ9-四氢大麻酚(Δ9-THC)的化学异构体Δ8-四氢大麻酚(Δ8-THC)的流行程度和可获得性已急剧增加,但尚无对照研究直接比较汽化Δ8-THC和Δ9-THC的效果。

方法

20名过去一个月内未接触过大麻的健康成年人,以受试者内、双盲、交叉设计完成了5次随机门诊疗程。参与者使用Mighty Medic蒸发器吸入Δ8-THC(10、20、40毫克)、Δ9-THC(20毫克)或安慰剂(蒸馏水)。测量指标包括主观药物效应、认知/心理运动表现、吸气流速形态、生命体征以及Δ8-THC、Δ9-THC及其代谢物的全血浓度。

结果

所有Δ8-THC剂量和Δ9-THC均产生了与安慰剂不同的主观药物效应。20毫克Δ9-THC引起的“药物效应”和“不适感”评分比10毫克Δ8-THC更强;Δ8-THC和Δ9-THC之间的其他主观效应无差异。与安慰剂相比,20毫克Δ9-THC损害了DRUID表现;在认知/心理运动测量方面,各条件之间未观察到其他显著差异。Δ8-THC不同剂量之间观察到的药效学差异很少。出现了补偿性抽吸的证据,在较低的Δ8-THC剂量和安慰剂条件下,抽吸时间更长/体积更大。血液大麻素浓度显示,Δ8-THC的代谢与Δ9-THC不同,Δ8-THC暴露后形成的具有精神活性的11-羟基代谢物较少。

结论

各种剂量的汽化Δ8-THC引起的精神活性效应与汽化Δ9-THC相当,考虑到Δ8-THC的效力较低且通常被认为比Δ9-THC危害/毒性更小,这一点值得注意。大麻素的效应强度由几个因素决定,包括剂量、给药途径,以及对于吸入方法而言的抽吸行为。这些数据应在未来的药物政策和公众教育倡议中予以考虑。

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