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

IF 3.9 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2025-04-21 DOI:10.1016/j.drugalcdep.2025.112684

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

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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, 40 mg), Δ9-THC (20 mg), 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. 20 mg Δ9-THC elicited stronger ratings of “drug effect” and “unpleasant” than 10 mg Δ8-THC; no other subjective effects differed between Δ8-THC and Δ9-THC. 20 mg 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.

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一项比较汽化δ -8-四氢大麻酚和δ -9-四氢大麻酚在健康成人中的急性作用的受试者内交叉试验

背景：Δ9-tetrahydrocannabinol （Δ9-THC）的化学异构体Δ8-tetrahydrocannabinol （Δ8-THC）的患病率和可及性急剧增加，但没有对照研究直接比较蒸发Δ8-THC和Δ9-THC的效果。方法20名过去一个月没有大麻接触的健康成年人在受试者内、双盲、交叉设计中随机完成5次门诊治疗。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）。测量包括主观药物效应、认知/精神运动表现、呼吸地形、生命体征和Δ8-THC、Δ9-THC及其代谢物的全血浓度。结果Δ8-THC剂量和Δ9-THC均产生不同于安慰剂的主观药物效应。20 mg Δ9-THC对“药效”和“不愉快”的评分高于10 mg Δ8-THC；其他主观效应在Δ8-THC和Δ9-THC之间没有差异。20 mg Δ9-THC与安慰剂相比，DRUID表现受损；在认知/精神运动测量方面，两组间未观察到其他显著差异。Δ8-THC剂量之间几乎没有药效学差异。代偿性吞吐的证据出现了，在较低的Δ8-THC剂量和安慰剂下吞吐的时间更长/更大。血液大麻素浓度显示Δ8-THC代谢与Δ9-THC不同，Δ8-THC暴露后形成的精神活性11-OH代谢物较少。结论不同剂量的Δ8-THC汽化剂所产生的精神活性作用与Δ9-THC汽化剂相当，值得注意的是，Δ8-THC的效力较弱，并且通常被认为比Δ9-THC的危害/中毒程度更小。大麻素的影响程度由几个因素决定，包括剂量，给药途径，以及吸入方法，雾化行为。这些数据应该在未来的毒品政策和公共教育活动中加以考虑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug and alcohol dependence 医学-精神病学

CiteScore

7.40

自引率

7.10%

发文量

409

审稿时长

41 days

期刊介绍： Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.