A single dose of cannabidiol modulates the relationship between hippocampal glutamate and learning-related prefrontal activation in individuals at Clinical High Risk of Psychosis

IF 2.4 4区医学 Q3 CLINICAL NEUROLOGY

Psychiatry Research: Neuroimaging Pub Date : 2026-01-01 Epub Date: 2025-11-25 DOI:10.1016/j.pscychresns.2025.112095

Yiling Shi , Cathy Davies , Robin Wilson , Elizabeth Appiah-Kusi , David J. Lythgoe , Gemma Modinos , Sagnik Bhattacharyya

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引用次数: 0

Abstract

Background

Cannabidiol (CBD) is being studied as a potential intervention for the people at clinical high risk for psychosis (CHR), though the mechanisms underlying its effects are not fully understood. Previous studies indicate that a single dose of CBD can normalize alterations in memory-related brain activation and modulate hippocampal glutamate levels in the early stages of psychosis. This study aimed to examine the acute effects of CBD on the relationship between hippocampal glutamate levels and brain activation during verbal memory in individuals at CHR.

Methods

A total of thirty-three participants (n = 33) at CHR were randomly assigned to receive a single 600 mg dose of CBD (CHR-CBD) or a placebo capsule (CHR-PLB). Age-matched healthy controls (HC) (n = 19) received no study drugs. Participants underwent MRI scanning while performing a verbal learning task, and proton magnetic resonance spectroscopy to measure hippocampal glutamate levels. Effect of group x hippocampal glutamate interactions on brain activation was tested.

Results

CHR-PLB showed positive correlation between hippocampal glutamate levels and dorsolateral prefrontal cortex (dlPFC) (Pcorr. = 0.0039) activation compared to HC during both verbal encoding and recall. Under a single dose of CBD, the glutamate-dlPFC activation relationship was negative and significantly different compared to placebo in CHR individuals (Pcorr. = 0.0001) during both verbal encoding and recall. The reversed correlation in CBD group was also observed in the parahippocampal gyrus (Pcorr. = 0.0022) and amygdala (Pcorr. = 0.0019) during verbal recall.

Conclusions

These findings suggest that CBD may normalise disrupted hippocampal–prefrontal glutamatergic coupling in CHR, highlighting its potential to target the neurochemical mechanisms underlying cognitive impairment.

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单剂量大麻二酚调节临床精神病高危个体海马谷氨酸和学习相关前额叶激活之间的关系。

背景：大麻二酚（CBD）作为临床精神病高危人群（CHR）的潜在干预措施正在被研究，尽管其作用机制尚不完全清楚。先前的研究表明，在精神病的早期阶段，单剂量的CBD可以使记忆相关的大脑激活和海马谷氨酸水平的改变正常化。本研究旨在研究CBD对CHR个体言语记忆期间海马谷氨酸水平和大脑激活之间关系的急性影响。方法：共有33名CHR参与者（n = 33）被随机分配接受单剂量600 mg CBD （cr -CBD）或安慰剂胶囊（cr - plb）。年龄匹配的健康对照（HC）（n = 19）未接受研究药物。参与者在执行口头学习任务时接受核磁共振扫描，并使用质子磁共振波谱测量海马谷氨酸水平。观察x组海马谷氨酸相互作用对脑活化的影响。结果：cr - plb显示海马谷氨酸水平与背外侧前额叶皮质（dlPFC）呈正相关。= 0.0039)，在言语编码和回忆过程中都比HC激活。在单剂量CBD下，CHR个体的谷氨酸- dlpfc激活关系为负，与安慰剂相比有显著差异（Pcorr）。= 0.0001)。CBD组海马旁回（Pcorr）呈负相关。= 0.0022)和杏仁核(Pcorr。= 0.0019)。结论：这些发现表明，CBD可能使CHR中受损的海马-前额叶谷氨酸能偶联正常化，突出了其针对认知障碍的神经化学机制的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychiatry Research: Neuroimaging 医学-精神病学

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

22.5 weeks

期刊介绍： The Neuroimaging section of Psychiatry Research publishes manuscripts on positron emission tomography, magnetic resonance imaging, computerized electroencephalographic topography, regional cerebral blood flow, computed tomography, magnetoencephalography, autoradiography, post-mortem regional analyses, and other imaging techniques. Reports concerning results in psychiatric disorders, dementias, and the effects of behaviorial tasks and pharmacological treatments are featured. We also invite manuscripts on the methods of obtaining images and computer processing of the images themselves. Selected case reports are also published.