Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans
Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans
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DOI：
10.1038/npp.2012.8
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发表时间：
2012-06-01
影响因子：
7.6
通讯作者：
Mathalon, Daniel
中科院分区：
文献类型：
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作者：
D'Souza, Deepak Cyril;Fridberg, Daniel J.;Mathalon, Daniel
大麻素在人类中诱导许多感知改变和认知缺陷。然而，这些缺陷的神经相关性仍然难以捉摸。目前的研究检查了δ-9-四氢大麻酚（δ（9）-THC）对人类信息处理的心理生理指标的急性剂量相关影响。健康受试者（n = 26）完成了三个试验日，在此期间，他们以受试者内、双盲、随机、交叉和平衡设计接受静脉内Delta（9）-THC（安慰剂，0.015和0.03 mg/kg）。在给药前和给药后收集心理生理学数据（脑电图），同时受试者进行事件相关电位（ERP）任务，该任务已知是注意力和认知的有效指标（三刺激听觉“古怪”P300任务）。Δ（9）-THC剂量依赖性地降低靶P300 b和新奇P300 a的振幅。Delta（9）-THC对P300 a或P300 b的潜伏期或P300之前的早期感觉诱发ERP成分（N100）没有任何影响。同时，Delta（9）-THC以剂量依赖性方式诱导拟精神病效应、感知改变和主观“高”。Delta（9）-THC诱导的P3 b振幅降低与Delta（9）-THC诱导的感知改变相关。最后，检查大麻使用状况的探索性分析显示，尽管最近的大麻使用者对Delta（9）-THC的行为影响减弱，但在无大麻和最近的大麻使用者之间，Delta（9）-THC对P300 a/B振幅没有剂量相关的影响。总的来说，这些数据表明，在产生与大麻的已知特性一致的行为和主观效应的剂量下，Delta（9）-THC降低了P300 a和P300 b的振幅，而不改变这些ERP的潜伏期。因此，大麻素激动剂可能会破坏负责上下文更新和注意力自动定向的皮层过程，同时保持处理速度和早期感觉ERP组件不变。总的来说，研究结果表明，CB 1 R系统调节自上而下和自下而上的处理。Neuropsychopharmacology（2012）37，1632-1646; doi：10.1038/npp.2012.8; 2012年2月15日在线发表
Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Delta(9)-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n = 26) completed three test days during which they received intravenous Delta(9)-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory 'oddball' P300 task). Delta(9)-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Delta(9)-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Delta(9)-THC induced psychotomimetic effects, perceptual alterations, and subjective 'high' in a dose-dependent manner. Delta(9)-THC -induced reductions in P3b amplitude correlated with Delta(9)-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Delta(9)-THC, there were no dose-related effects of Delta(9)-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Delta(9)-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing. Neuropsychopharmacology (2012) 37, 1632-1646; doi:10.1038/npp.2012.8; published online 15 February 2012