Jacobs David S, Kohut Stephen J, Jiang Shan, Nikas Spyros P, Makriyannis Alexandros, Bergman Jack
Preclinical Pharmacology Laboratory.
Center for Drug Discovery, Northeastern University.
Exp Clin Psychopharmacol. 2016 Oct;24(5):320-330. doi: 10.1037/pha0000081. Epub 2016 Aug 15.
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
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)