# Cannabidiol Modulates Hippocampal Glutamate Function > **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637) > **Publisher:** CED Clinic (https://cedclinic.com) > **Canonical URL:** https://cedclinic.com/cannabidiol-hippocampal-glutamate-modulation/ > **Published:** 2026-04-25T14:08:25-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T11:54:49-04:00 > **Clinical Summary:** Explore cannabidiol hippocampal glutamate modulation and its role in normalizing brain activity in people at clinical high risk for psychosis. --- #### Clinical Takeaway A single dose of CBD reduced the association between elevated hippocampal glutamate and abnormal brain activity during memory tasks in people at clinical high risk for psychosis. This suggests CBD may work by normalizing glutamate signaling in brain regions critical for learning and memory. These findings support further investigation of CBD as a potential early intervention to prevent psychotic illness progression. ### #21 A single dose of cannabidiol modulates the relationship between hippocampal glutamate and learning-related prefrontal activation in individuals at Clinical High Risk of Psychosis. **Citation:** Shi Yiling et al. *A single dose of cannabidiol modulates the relationship between hippocampal glutamate and learning-related prefrontal activation in individuals at Clinical High Risk of Psychosis.* Psychiatry research. Neuroimaging. 2026. PMID: 41337954. **Study type:** Journal Article, Randomized Controlled Trial  |  **Topic area:** Cannabidiol  |  **CED Score:** 10 Design: 5 Journal: 0 N: 1 Recency: 3 Pop: 2 Human: 1 Risk: -2 **Quality Gate Alerts:** - Preclinical only **Methodological Considerations:** - Small sample — underpowered for subgroup analysis **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](https://cedclinic.com/acute-effects-partial-cb1-receptor-agonists-cognition/).  |  [View on PubMed ↗](https://pubmed.ncbi.nlm.nih.gov/41337954/)[DOI ↗](https://doi.org/10.1016/j.pscychresns.2025.112095) [https://cedclinic.com/contact/](https://cedclinic.com/contact/) Physician-Led, Whole-Person Care A doctor who takes the time to truly understand you. Personal care that starts with listening and is guided by experience and ingenuity. 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[Read More](https://cedclinic.com/cannabidiol-clinical-trials-psychosis-research/) [Cannabidiol Modulates Glutamate and Learning in Psychosis](https://cedclinic.com/cannabidiol-glutamate-psychosis-modulation/) Explore research on cannabidiol's modulation of glutamate and its effects on learning in individuals at risk for psychosis. [Explore Article](https://cedclinic.com/cannabidiol-glutamate-psychosis-modulation/) [Cannabinoid Clinical Trials: CBD, Psychosis & Brain Function](https://cedclinic.com/cbd-hippocampal-glutamate-modulation-psychosis-risk/) Review [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/) investigating cannabidiol's impact on hippocampal glutamate and brain function in psychosis risk. [View Trials](https://cedclinic.com/cbd-hippocampal-glutamate-modulation-psychosis-risk/) Have thoughts on this? 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