The Individual and Interactive Effects of Alpha-Pinene and Delta-9-Tetrahydrocannabinol in Healthy Adults.

Q1 Medicine
Medical Cannabis and Cannabinoids Pub Date : 2025-06-25 eCollection Date: 2025-01-01 DOI:10.1159/000547014
Lakshmi Kumar, Tory R Spindle, C Austin Zamarripa, Harrison J Elder, Ethan B Russo, George Bigelow, Ryan Vandrey
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引用次数: 0

Abstract

Introduction: Cannabis contains hundreds of chemical constituents beyond delta-9-tetrahydrocannabinol (Δ9-THC), which is thought to be the primary driver of most of its acute pharmacodynamic effects. The entourage effect theory asserts that the pharmacological and therapeutic effects of cannabis are not solely attributable to Δ9-THC but are influenced by other constituents, such as minor cannabinoids and terpenes, through distinct pharmacological action. However, empirical studies that have systematically evaluated this theory in humans remain limited. This study tested the hypothesis that the terpene α-pinene can attenuate the acute memory-impairing effects of inhaled Δ9-THC in humans.

Methods: Participants (N = 19; last cannabis use 39 days, on average, prior to first test session [SD = 84; range = 2-365]) completed six double-blind outpatient drug administration sessions during which they inhaled, using a Mighty Medic hand-held vaporizer, α-pinene alone (15 mg), Δ9-THC alone (30 mg), Δ9-THC and α-pinene together (30 mg Δ9-THC + 0.5 mg α-pinene; 30 mg Δ9-THC + 5 mg α-pinene; 30 mg Δ9-THC + 15 mg α-pinene), or placebo (ambient air) in a randomized order. Outcomes, which were collected up to 6 h post-drug exposure, included subjective drug effects, cognitive/psychomotor performance, and vital signs.

Results: Administration of 15 mg α-pinene alone produced no significant pharmacodynamic effects compared to placebo. Administration of 30 mg Δ9-THC alone elicited subjective, cognitive, and physiological effects consistent with acute Δ9-THC-dominant cannabis exposure, including impairment of cognitive performance and working memory ability compared to placebo. The co-administration of α-pinene with Δ9-THC did not mitigate Δ9-THC-induced memory impairment or significantly alter other acute subjective, cognitive, or physiological effects.

Conclusions: Inhaled α-pinene, at doses at and above those naturally found in cannabis flowers, did not mitigate Δ9-THC-induced cognitive impairments as hypothesized or influence other common acute effects of Δ9-THC in this sample of healthy adults. This result is inconsistent with some cannabis industry claims and speculation by some cannabis researchers. By systematically varying both Δ9-THC and terpene exposure and assessing their interaction across multiple pharmacodynamic domains, this work provides a model for future investigations into Δ9-THC-terpene interactions. As cannabis use continues to expand for both medicinal and non-medicinal purposes, more research is needed to better understand the acute effects of lesser studied chemical constituents of the plant and how they interact with predominant phytocannabinoids like Δ9-THC. This can inform cannabinoid drug development and product regulations.

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α -蒎烯和δ -9-四氢大麻酚在健康成人中的个体效应和相互作用。
简介:大麻含有数百种化学成分,除了delta-9-四氢大麻酚(Δ9-THC),这被认为是其大多数急性药效学效应的主要驱动因素。伴随效应理论认为,大麻的药理学和治疗效果不仅可归因于Δ9-THC,还可通过不同的药理作用受到其他成分的影响,如少量大麻素和萜烯。然而,在人类中系统评估这一理论的实证研究仍然有限。本研究验证了萜烯α-蒎烯可以减轻人体吸入Δ9-THC的急性记忆损伤作用的假设。方法:参与者(N = 19;最后一次使用大麻,平均39天,在第一次测试之前[SD = 84;范围= 2-365])完成了6个双盲门诊给药疗程,在此期间,他们使用Mighty Medic手持式汽化器吸入α-蒎烯单独(15毫克)、Δ9-THC单独(30毫克)、Δ9-THC和α-蒎烯一起(30毫克Δ9-THC + 0.5毫克α-蒎烯;30 mg Δ9-THC + 5 mg α-蒎烯;30毫克Δ9-THC + 15毫克α-蒎烯),或安慰剂(环境空气)随机排序。药物暴露后6小时收集的结果包括主观药物效应、认知/精神运动表现和生命体征。结果:单独给药15 mg α-蒎烯与安慰剂相比,没有显著的药效学作用。单独给药30 mg Δ9-THC引起与急性Δ9-THC-dominant大麻暴露一致的主观、认知和生理效应,包括与安慰剂相比认知表现和工作记忆能力的损害。α-蒎烯与Δ9-THC联合用药并不能减轻Δ9-THC-induced记忆损伤或显著改变其他急性主观、认知或生理效应。结论:在该健康成人样本中,吸入α-蒎烯的剂量等于或高于大麻花中天然含量的α-蒎烯,并没有像假设的那样减轻Δ9-THC-induced认知障碍,也没有影响Δ9-THC的其他常见急性效应。这一结果与一些大麻行业的说法和一些大麻研究人员的猜测不一致。通过系统地改变Δ9-THC和萜烯暴露,并评估它们在多个药效学领域的相互作用,这项工作为未来研究Δ9-THC-terpene相互作用提供了一个模型。随着大麻用于医疗和非医疗用途的不断扩大,需要进行更多的研究,以更好地了解这种植物中较少研究的化学成分的急性作用,以及它们如何与Δ9-THC等主要植物大麻素相互作用。这可以为大麻素药物开发和产品监管提供信息。
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
Medical Cannabis and Cannabinoids
Medical Cannabis and Cannabinoids Medicine-Complementary and Alternative Medicine
CiteScore
6.00
自引率
0.00%
发文量
18
审稿时长
18 weeks
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