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大麻二酚对Δ⁹-四氢大麻酚(Δ⁹-THC)诱导的停止信号任务表现破坏的急性和慢性影响。

Acute and chronic effects of cannabidiol on Δ⁹-tetrahydrocannabinol (Δ⁹-THC)-induced disruption in stop signal task performance.

作者信息

Jacobs David S, Kohut Stephen J, Jiang Shan, Nikas Spyros P, Makriyannis Alexandros, Bergman Jack

机构信息

Preclinical Pharmacology Laboratory.

Center for Drug Discovery, Northeastern University.

出版信息

Exp Clin Psychopharmacol. 2016 Oct;24(5):320-330. doi: 10.1037/pha0000081. Epub 2016 Aug 15.

Abstract

Recent clinical and preclinical research has suggested that cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) have interactive effects on measures of cognition; however, the nature of these interactions is not yet fully characterized. To address this, we investigated the effects of Δ9-THC and CBD independently and in combination with proposed therapeutic dose ratios of 1:1 and 1:3 Δ9-THC:CBD in adult rhesus monkeys (n = 6) performing a stop signal task (SST). Additionally, the development of tolerance to the effects of Δ9-THC on SST performance was evaluated by determining the effects of acutely administered Δ9-THC (0.1-3.2 mg/kg), during a 24-day chronic Δ9-THC treatment period with Δ9-THC alone or in combination with CBD. Results indicate that Δ9-THC (0.032-0.32 mg/kg) dose-dependently decreased go success but did not alter go reaction time (RT) or stop signal RT (SSRT); CBD (0.1-1.0 mg/kg) was without effect on all measures and, when coadministered in a 1:1 dose ratio, did not exacerbate or attenuate the effects of Δ9-THC. When coadministered in a 1:3 dose ratio, CBD (1.0 mg/kg) attenuated the disruptive effects of 0.32 mg/kg Δ9-THC but did not alter the effects of other Δ9-THC doses. Increases in ED50 values for the effects of Δ9-THC on SST performance were apparent during chronic Δ9-THC treatment, with little evidence for modification of changes in sensitivity by CBD. These results indicate that CBD, when combined with Δ9-THC in clinically available dose ratios, does not exacerbate and, under restricted conditions may even attenuate, Δ9-THC's behavioral effects. (PsycINFO Database Record

摘要

近期的临床和临床前研究表明,大麻二酚(CBD)和Δ9-四氢大麻酚(Δ9-THC)对认知指标具有交互作用;然而,这些相互作用的性质尚未完全明确。为解决这一问题,我们在成年恒河猴(n = 6)执行停止信号任务(SST)时,分别研究了Δ9-THC和CBD的作用,以及以1:1和1:3的Δ9-THC:CBD治疗剂量比联合使用时的效果。此外,通过确定在单独使用Δ9-THC或与CBD联合使用的24天慢性Δ9-THC治疗期间急性给予Δ9-THC(0.1 - 3.2 mg/kg)的效果,评估了对Δ9-THC对SST表现影响的耐受性发展。结果表明,Δ9-THC(0.032 - 0.32 mg/kg)剂量依赖性地降低了“走”成功的概率,但未改变“走”反应时间(RT)或停止信号反应时间(SSRT);CBD(0.1 - 1.0 mg/kg)对所有指标均无影响,并且以1:1剂量比共同给药时,既没有加剧也没有减弱Δ9-THC的作用。当以1:3剂量比共同给药时,CBD(1.0 mg/kg)减弱了0.32 mg/kg Δ9-THC的干扰作用,但未改变其他Δ9-THC剂量的作用。在慢性Δ9-THC治疗期间,Δ9-THC对SST表现影响的半数有效剂量(ED50)值明显增加,几乎没有证据表明CBD会改变敏感性变化。这些结果表明,当CBD与Δ9-THC以临床可用剂量比联合使用时,不会加剧,并且在受限条件下甚至可能减弱Δ9-THC的行为效应。(PsycINFO数据库记录)

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