一项比较健康成人口服-8-四氢大麻酚和-9-四氢大麻酚急性效应的受试者内交叉试验

IF 3.9 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2025-04-12 DOI:10.1016/j.drugalcdep.2025.112676

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

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引用次数: 0

摘要

背景：近年来，含有Δ8-tetrahydrocannabinol （Δ8-THC）的口服产品越来越受欢迎，Δ8-tetrahydrocannabinol （Δ8-THC）是大麻主要精神活性物质Δ9-tetrahydrocannabinol （Δ9-THC）的化学异构体。口服Δ8-THC的行为效应和药代动力学特征仍然很差。方法19名过去一个月没有大麻素暴露的健康成年人在受试者内、双盲、交叉设计中完成了5次随机门诊治疗。参与者摄入含有Δ8-THC（10、20、40毫克）、Δ9-THC（20毫克）或安慰剂的布朗尼。测量包括全血大麻素浓度、主观药物效应、认知/精神运动表现和生命体征。结果全血大麻素浓度在给药后2 ~ 4 h达到峰值，呈剂量顺序。相同剂量下，Δ8-THC的精神活性11-OH代谢物明显低于Δ9-THC。Δ8-THC在多个领域产生剂量依赖的主观效应，与安慰剂不同。与20毫克Δ9-THC相比，20毫克Δ8-THC的“感觉药物效应”、负面主观效应、认知/精神运动障碍和心率增加的评分明显较低。40 mg Δ8-THC和20 mg Δ9-THC之间没有观察到药效学差异。与20毫克Δ9-THC相比，20毫克和40毫克Δ8-THC都产生了相当的积极主观效应（例如，药物喜好），这表明类似的滥用潜力。ConclusionΔ8-THC表现出与Δ9-THC在质量上相似的剂量依赖性精神活性作用，但效力降低，可能是由于其11-OH代谢物的生物转化较低。重要的是，更高剂量的Δ8-THC抵消了降低的效力，因为40毫克Δ8-THC和20毫克Δ9-THC产生了相似的效果；考虑到吸食大麻产品的人通常认为Δ8-THC比Δ9-THC危害更小或更令人陶醉，这一点值得注意。这些发现为监管决策和公众教育提供了信息，尽管需要对新兴大麻素进行进一步研究。

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

Background

Oral products containing Δ8-tetrahydrocannabinol (Δ8-THC), a chemical isomer of the primary psychoactive consistent of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC), have increased in popularity in recent years. The behavioral effects and pharmacokinetics of oral Δ8-THC remain poorly characterized.

Methods

Nineteen healthy adults with no past-month cannabinoid exposure completed five randomized outpatient sessions in a within-subjects, double-blind, crossover design. Participants ingested a brownie containing Δ8-THC (10, 20, 40 mg), Δ9-THC (20 mg), or placebo. Measures included whole blood cannabinoid concentrations, subjective drug effects, cognitive/psychomotor performance, and vital signs.

Results

Whole blood cannabinoid concentrations peaked between 2 and 4 h post-dose in a dose-orderly manner. The psychoactive 11-OH metabolite of Δ8-THC was markedly lower than that of Δ9-THC at the same dose. Δ8-THC produced dose-dependent subjective effects across multiple domains, differing from placebo. Compared to 20 mg Δ9-THC, 20 mg Δ8-THC resulted in significantly lower ratings of “feel drug effect,” negative subjective effects, cognitive/psychomotor impairment, and heart rate increases. No pharmacodynamic differences were observed between 40 mg Δ8-THC and 20 mg Δ9-THC. Both 20 mg and 40 mg Δ8-THC produced comparable positive subjective effects (e.g., drug liking) to 20 mg Δ9-THC, suggesting similar misuse potential.

Conclusion

Δ8-THC demonstrated dose-dependent psychoactive effects qualitatively similar to Δ9-THC but with reduced potency, possibly due to lower biotransformation to its 11-OH metabolite. Importantly, higher doses of Δ8-THC offset reduced potency, as 40 mg Δ8-THC and 20 mg Δ9-THC produced similar effects; this is noteworthy considering people who consume cannabis products generally perceive Δ8-THC as less harmful or intoxicating than Δ9-THC. These findings inform regulatory decisions and public education, though further research on emergent cannabinoids is needed.

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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.