Lile Joshua A, Wesley Michael J, Kelly Thomas H, Hays Lon R
Departments of aBehavioral SciencebPsychiatrycInternal Medicine, College of MedicinedDepartment of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky, USA.
Behav Pharmacol. 2016 Apr;27(2-3 Spec Issue):215-24. doi: 10.1097/FBP.0000000000000187.
The aim of the present study was to examine a potential mechanism of action of gabapentin to manage cannabis-use disorders by determining the interoceptive effects of gabapentin in cannabis users discriminating [INCREMENT]-tetrahydrocannabinol ([INCREMENT]-THC) using a pharmacologically selective drug-discrimination procedure. Eight cannabis users learned to discriminate 30 mg oral [INCREMENT]-THC from placebo and then received gabapentin (600 and 1200 mg), [INCREMENT]-THC (5, 15, and 30 mg), and placebo alone and in combination. Self-report, task performance, and physiological measures were also collected. [INCREMENT]-THC served as a discriminative stimulus, produced positive subjective effects, elevated heart rate, and impaired psychomotor performance. Both doses of gabapentin substituted for the [INCREMENT]-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of [INCREMENT]-THC when administered alone. When administered concurrently, gabapentin shifted the discriminative-stimulus effects of [INCREMENT]-THC leftward/upward, and combinations of [INCREMENT]-THC and gabapentin generally produced larger effects on cannabinoid-sensitive outcomes relative to [INCREMENT]-THC alone. These results suggest that one mechanism by which gabapentin might facilitate cannabis abstinence is by producing effects that overlap with those of cannabinoids.
本研究的目的是通过使用药理学选择性药物辨别程序,确定加巴喷丁在辨别Δ⁹-四氢大麻酚(Δ⁹-THC)的大麻使用者中的内感受效应,来检验加巴喷丁治疗大麻使用障碍的潜在作用机制。八名大麻使用者学会了将口服30毫克的Δ⁹-THC与安慰剂区分开来,然后单独或联合接受加巴喷丁(600毫克和1200毫克)、Δ⁹-THC(5毫克、15毫克和30毫克)以及安慰剂。还收集了自我报告、任务表现和生理指标。Δ⁹-THC作为一种辨别性刺激,产生了积极的主观效应、心率升高以及心理运动表现受损。两种剂量的加巴喷丁都替代了Δ⁹-THC的辨别性刺激,并产生了与单独使用Δ⁹-THC时重叠的主观和表现受损效应。当同时给药时,加巴喷丁使Δ⁹-THC的辨别性刺激效应向左/向上移动,并且与单独使用Δ⁹-THC相比,Δ⁹-THC和加巴喷丁的组合通常对大麻素敏感结果产生更大的影响。这些结果表明,加巴喷丁促进大麻戒断的一种机制可能是产生与大麻素重叠的效应。