# Clinical Research on CBD’s Impact on Hippocampal Glutamate in Psychosis > **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637) > **Publisher:** CED Clinic (https://cedclinic.com) > **Canonical URL:** https://cedclinic.com/cbd-hippocampal-glutamate-modulation-psychosis/ > **Published:** 2026-03-25T21:44:39-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T11:57:32-04:00 > **Clinical Summary:** Explore CBD hippocampal glutamate modulation psychosis research showing CBD’s role in brain activity and memory in early psychosis risk individuals. --- #### Clinical Takeaway In a study of individuals at clinical high risk for psychosis, a single dose of CBD influenced the relationship between hippocampal glutamate levels and prefrontal brain activity during verbal memory tasks. This suggests CBD may work by modulating glutamate signaling in memory-related brain circuits, which are known to be disrupted in early psychosis. These findings help clarify a potential neurochemical mechanism behind CBD’s observed effects on memory function in this population. ### #19 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](https://cedclinic.com/episodic-memory-cannabis-impairment-study/) 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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[Learn More](https://cedclinic.com/cannabidiol-glutamate-modulation-psychosis/) [Cannabidiol Effects on Glutamate and Learning in Psychosis Prevention](https://cedclinic.com/cannabidiol-clinical-trials-psychosis-research/) Study on cannabidiol’s impact on glutamate and learning processes in psychosis prevention strategies. [Explore Study](https://cedclinic.com/cannabidiol-clinical-trials-psychosis-research/) Have thoughts on this? 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