Zamarripa C Austin, Spindle Tory R, Schriefer Destiny, Cone Edward J, Winecker Ruth E, Flegel Ronald, Hayes Eugene, Davis Lisa S, Kuntz David, Vandrey Ryan
Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Drug Alcohol Depend. 2025 Jul 1;272:112676. doi: 10.1016/j.drugalcdep.2025.112676. Epub 2025 Apr 12.
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.
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, 40mg), Δ9-THC (20mg), or placebo. Measures included whole blood cannabinoid concentrations, subjective drug effects, cognitive/psychomotor performance, and vital signs.
Whole blood cannabinoid concentrations peaked between 2 and 4h 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 20mg Δ9-THC, 20mg 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 40mg Δ8-THC and 20mg Δ9-THC. Both 20mg and 40mg Δ8-THC produced comparable positive subjective effects (e.g., drug liking) to 20mg Δ9-THC, suggesting similar misuse potential.
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 40mg Δ8-THC and 20mg 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.
含有Δ8-四氢大麻酚（Δ8-THC）的口服产品近年来越来越受欢迎，Δ8-THC是大麻主要精神活性成分Δ9-四氢大麻酚（Δ9-THC）的一种化学异构体。口服Δ8-THC的行为效应和药代动力学仍未得到充分表征。
19名在过去一个月内未接触过大麻素的健康成年人，以受试者内、双盲、交叉设计完成了五次随机门诊疗程。参与者食用了含有Δ8-THC（10、20、40毫克）、Δ9-THC（20毫克）或安慰剂的布朗尼蛋糕。测量指标包括全血大麻素浓度、主观药物效应、认知/心理运动表现和生命体征。
全血大麻素浓度在给药后2至4小时达到峰值，呈剂量依赖性。在相同剂量下，Δ8-THC的精神活性11-羟基代谢物明显低于Δ9-THC。Δ8-THC在多个领域产生剂量依赖性主观效应，与安慰剂不同。与20毫克Δ9-THC相比，20毫克Δ8-THC导致“感觉药物效应”、负面主观效应、认知/心理运动损害和心率增加的评分显著降低。40毫克Δ8-THC和20毫克Δ9-THC之间未观察到药效学差异。20毫克和40毫克Δ8-THC产生的积极主观效应（如药物喜好）与20毫克Δ9-THC相当，表明滥用潜力相似。
Δ8-THC表现出与Δ9-THC在质量上相似的剂量依赖性精神活性效应，但效力较低，这可能是由于其向11-羟基代谢物的生物转化较低。重要的是，更高剂量的Δ8-THC抵消了效力降低的影响，因为40毫克Δ8-THC和20毫克Δ9-THC产生了相似的效果；考虑到食用大麻产品的人通常认为Δ8-THC比Δ9-THC危害更小或致醉性更低，这一点值得注意。这些发现为监管决策和公众教育提供了参考，不过仍需要对新兴大麻素进行进一步研究。
