Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.
Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.
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DOI：
10.1038/s41598-017-14203-4
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发表时间：
2017-11-03
影响因子：
4.6
通讯作者：
McGuire P
中科院分区：
文献类型：
--
作者：
Bhattacharyya S;Egerton A;Kim E;Rosso L;Riano Barros D;Hammers A;Brammer M;Turkheimer FE;Howes OD;McGuire P
大麻是世界上使用最广泛的非法药物，使用大麻与急性焦虑和正常使用后的焦虑症有关。这些效应的确切神经和受体基础还没有在人类身上进行测试。我们采用功能磁共振成像(FMRI)和正电子发射断层扫描(PET)相结合的方法，研究了大麻的主要精神活性成分β-9-四氢大麻酚(Delta-9-THC)在处理恐惧刺激时对焦虑和杏仁核反应的影响是否与其主要中枢分子靶标大麻素-1(CB1)受体在人体内的局部可获得性有关。对14名健康男性进行了两次功能核磁共振研究，每次间隔一个月，在他们进行恐惧处理任务的同时，口服Delta9-THC(10 mg)或安慰剂。使用CB1反向激动剂放射性配基[11C]MePPEP的PET研究CB1受体的基线可用性。与安慰剂条件相比，Delta-9-THC在处理恐惧的同时诱导焦虑并调节右侧杏仁核的激活。这两种作用与右侧杏仁核中CB1受体的可获得性呈正相关。这些结果表明，大麻对男性焦虑的急性影响是通过β-9-THC对杏仁核功能的调节而实现的，这些影响的程度与CB1受体的局部可获得性有关。
Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [11C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors.
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影响因子：
--
作者：
Fusar-Poli, Paolo;Crippa, Jose A.;McGuire, Philip K.
通讯作者：
McGuire, Philip K.
影响因子：
5.7
作者：
Ettrup, Anders;Svarer, Claus;Knudsen, Gitte Moos
通讯作者：
Knudsen, Gitte Moos
影响因子：
5.7
作者：
Hammers, Alexander;Asselin, Marie-Claude;Koepp, Matthias J.
通讯作者：
Koepp, Matthias J.
影响因子：
5.7
作者：
Friman, O;Borga, M;Knutsson, H
通讯作者：
Knutsson, H
影响因子：
5.7
作者：
Riaño Barros DA;McGinnity CJ;Rosso L;Heckemann RA;Howes OD;Brooks DJ;Duncan JS;Turkheimer FE;Koepp MJ;Hammers A
通讯作者：
Hammers A