Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing
Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing
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DOI：
10.1001/archgenpsychiatry.2008.519
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
McGuire, Philip K.
中科院分区：
文献类型：
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作者：
Fusar-Poli, Paolo;Crippa, Jose A.;McGuire, Philip K.
背景：大麻的使用既可以增加也可以减少人类的焦虑。这些作用的神经生理基础是未知的。目的：探讨大麻中2种主要精神活性成分（δ 9-四氢大麻酚[δ 9-THC]和大麻二酚[CBD]）对情绪加工过程中脑区域功能的影响。设计：研究对象在3个不同的场合使用事件相关功能磁共振成像范式，同时观察隐含引起不同程度焦虑的面孔。在双盲、随机、安慰剂对照设计中，每次扫描之前都摄入10毫克德尔塔9-四氢大麻酚、600毫克CBD或安慰剂。参与者：15名健康、英语为母语、右撇子、一生中使用大麻15次或更少的男性。主要结果测量：脑区域激活（血氧水平依赖性反应），皮电活动（皮肤电导反应[SCR]），客观和主观焦虑评分。结果：德尔塔9-四氢大麻酚增加焦虑，以及中毒、镇静和精神病症状的水平，而在给予CBD后，焦虑有减少的趋势。在处理强烈恐惧面孔的过程中，δ 9-四氢大麻酚增加了SCR波动的次数，而CBD减少了SCR波动的次数。大麻二酚减弱了受试者在处理强烈恐惧面孔时杏仁核和扣带前后皮层的血氧水平依赖信号，其对杏仁核和扣带前皮层反应的抑制与SCR波动的同时降低相关。δ 9-四氢大麻酚主要调节额叶和顶叶区的激活。结论：δ 9-四氢大麻酚和CBD对恐惧面孔的神经、皮肤电反应和症状反应有明显不同的影响。CBD对边缘和副边缘区域激活的影响可能有助于其减少自主神经觉醒和主观焦虑的能力，而Delta 9-THC的焦虑效应可能与大脑其他区域的作用有关。
Context: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.Objective: To investigate the effects of 2 main psycho-active constituents of Cannabis sativa (Delta 9-tetrahydrocannabinol [Delta 9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing.Design: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta 9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design.Participants: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life.Main Outcome Measures: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety.Results: Delta 9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta 9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta 9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas.Conclusions: Delta 9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta 9-THC may be related to effects in other brain regions.