O'Neill Aisling, Wilson Robin, Blest-Hopley Grace, Annibale Luciano, Colizzi Marco, Brammer Mick, Giampietro Vincent, Bhattacharyya Sagnik
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Section of Psychiatry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Psychol Med. 2021 Mar;51(4):596-606. doi: 10.1017/S0033291719003519. Epub 2020 Jan 29.
Recent evidence suggests that cannabidiol (CBD), a non-intoxicating ingredient present in cannabis extract, has an antipsychotic effect in people with established psychosis. However, the effect of CBD on the neurocognitive mechanisms underlying psychosis is unknown.
Patients with established psychosis on standard antipsychotic treatment were studied on separate days at least one week apart, to investigate the effects of a single dose of orally administered CBD (600 mg) compared to a matched placebo (PLB), using a double-blind, randomized, PLB-controlled, repeated-measures, within-subject cross-over design. Three hours after taking the study drug participants were scanned using a block design functional magnetic resonance imaging (fMRI) paradigm, while performing a verbal paired associate learning task. Fifteen psychosis patients completed both study days, 13 completed both scanning sessions. Nineteen healthy controls (HC) were also scanned using the same fMRI paradigm under identical conditions, but without any drug administration. Effects of CBD on brain activation measured using the blood oxygen level-dependent hemodynamic response fMRI signal were studied in the mediotemporal, prefrontal, and striatal regions of interest.
Compared to HC, psychosis patients under PLB had altered prefrontal activation during verbal encoding, as well as altered mediotemporal and prefrontal activation and greater mediotemporal-striatal functional connectivity during verbal recall. CBD attenuated dysfunction in these regions such that activation under its influence was intermediate between the PLB condition and HC. CBD also attenuated hippocampal-striatal functional connectivity and caused trend-level symptom reduction in psychosis patients.
This suggests that normalization of mediotemporal and prefrontal dysfunction and mediotemporal-striatal functional connectivity may underlie the antipsychotic effects of CBD.
最近有证据表明，大麻提取物中的一种无致幻作用成分大麻二酚（CBD）对已患精神病的人具有抗精神病作用。然而，CBD对精神病潜在神经认知机制的影响尚不清楚。
对接受标准抗精神病治疗的已患精神病患者，在至少相隔一周的不同日期进行研究，采用双盲、随机、安慰剂对照、重复测量、受试者内交叉设计，比较单次口服CBD（600毫克）与匹配安慰剂（PLB）的效果。服用研究药物三小时后，参与者在执行言语配对联想学习任务时，使用组块设计功能磁共振成像（fMRI）范式进行扫描。15名精神病患者完成了两个研究日，13名完成了两次扫描。19名健康对照者（HC）也在相同条件下使用相同的fMRI范式进行扫描，但未服用任何药物。在颞中、前额叶和纹状体感兴趣区域研究了CBD对使用血氧水平依赖血流动力学反应fMRI信号测量的脑激活的影响。
与HC相比，服用PLB的精神病患者在言语编码过程中前额叶激活改变，在言语回忆过程中颞中及前额叶激活改变，且颞中-纹状体功能连接增强。CBD减轻了这些区域的功能障碍，使其影响下的激活介于PLB组和HC之间。CBD还减弱了海马-纹状体功能连接，并使精神病患者的症状有减轻趋势。
这表明颞中及前额叶功能障碍和颞中-纹状体功能连接的正常化可能是CBD抗精神病作用的基础。
