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J Psychopharmacol. 2025 Aug 21:2698811251360745. doi: 10.1177/02698811251360745. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabis constituents, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), show distinct pharmacological profiles with therapeutic relevance for neurological and psychiatric conditions. THC exerts euphoric effects primarily via CB1 receptor activation, while CBD displays non-euphoric properties affecting various pathways.

AIMS: This study evaluated the effects of THC, CBD, and their combination on brain functional connectivity (FC) and cerebral blood flow (CBF) using multimodal neuroimaging.

METHODS: Adult male Sprague Dawley rats received intraperitoneal doses of 10 mg/kg THC, 150 mg/kg CBD, 10.8:10 mg/kg THC:CBD, or vehicle. Resting-state blood oxygenation level dependent magnetic resonance imaging and arterial spin labelling assessed FC and CBF, approximately 2 h after drug administration. Graph-theory metrics and seed-based analyses identified connectivity and perfusion alterations, while plasma analyses determined cannabinoid concentrations.

RESULTS: THC increased whole-brain FC and clustering coefficient, with elevated CBF in cortical and subcortical regions. CBD decreased FC metrics without affecting CBF, while THC:CBD induced moderate increases in both. Seed-based analysis revealed THC-driven increases in cortical-hippocampal and cortical-striatal connectivity, attenuated in the THC:CBD group. A multivariate combined analysis of FC and CBF revealed a divergent pattern of changes induced by each drug.

CONCLUSIONS: In conclusion, we show that THC and CBD induce distinct neurophysiological profiles in rats, with THC increasing both connectivity and perfusion, moderated by CBD when combined. These findings corroborate existing knowledge about the effects of cannabinoids on the brain, while also supporting the potential of preclinical functional neuroimaging to delineate cannabinoid-induced endophenotypes, offering insights for therapeutic development.

PMID:40838351 | DOI:10.1177/02698811251360745

Hum Brain Mapp. 2025 Aug 15;46(12):e70304. doi: 10.1002/hbm.70304.

ABSTRACT

Numerous studies have emphasized the time-varying modular architecture of functional brain networks and its relevance to cognitive functions in healthy participants. However, how modular dynamics of resting-state functional networks change in schizophrenia and how these alterations relate to neurotransmitter and transcriptomic signatures have not been well elucidated. We harmonized resting-state fMRI data from a multi-site sample including 223 patients and 279 healthy controls and applied the multilayer network method to estimate the regional module switching rate (flexibility) of functional brain connectomes. We examined aberrant flexibility in patients relative to controls and explored its relations to neurotransmitter systems and postmortem gene expression. Compared with controls, patients with schizophrenia had significantly higher flexibility in the somatomotor and right visual regions, and lower flexibility in the left parahippocampal gyrus, right supramarginal gyrus, right frontal-operculum-insula, bilateral precuneus, posterior cingulate cortex, and bilateral inferior parietal gyrus. These alterations were associated with multiple neurotransmitter systems and weighted gene transcriptomic profiles. The most relevant genes were preferentially enriched for biological processes of transmembrane transport and brain development, specific cell types, and previously identified schizophrenia-related genes. This study reveals aberrant modular dynamics in schizophrenia and its relations to neurotransmitter systems and schizophrenia-related transcriptomic profiles, providing insights into the understanding of the pathophysiology underlying schizophrenia.

PMID:40838333 | PMC:PMC12368516 | DOI:10.1002/hbm.70304

Front Physiol. 2025 Aug 5;16:1633028. doi: 10.3389/fphys.2025.1633028. eCollection 2025.

ABSTRACT

INTRODUCTION: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by spontaneous or triggered electric shock-like facial pain. Microvascular decompression (MVD) is the most effective surgical intervention for classical TN that is refractory to medication. Recent advances in neuroimaging have enhanced visualization of the trigeminal nerve's vascular anatomy, deepening insights into TN pathophysiology and paving the way for improved diagnostics and therapies. Resting-state functional magnetic resonance imaging (rs-fMRI) has been extensively applied in studies of TN, uncovering alterations in brain activity, functional connectivity, cortical thickness and neural networks.

METHODS: Independent component analysis (ICA) presents a powerful alternative for analyzing fMRI data, offering several advantages over traditional region of interests (ROIs) approaches. The sensorimotor network playing a key role in pain modulation, identifying neuroimaging differences in the sensorimotor network is crucial for detecting and intervening in TN, Forty TN patients underwent MVD surgery, with follow-up assessments conducted 6 months postoperatively and twenty-five healthy controls (HC) were recruited and scanned with resting state fMRI (rs-fMRI). Group ICA was used to identify ROIs and assessed inter-group differences in neural activity using false discovery rate (FDR) correction.

RESULTS: Compared to the HC, increased activity was observed in the right frontal operculum cortex, right insular cortex, right inferior frontal gyrus (pars opercularis), and right frontal pole in TN patients. Conversely, decreased activity was found in the right cerebellum (lobule IX) and left cerebellum (lobules VIII and IX). Compared to the pre-surgery, increased activity was found in the right precentral gyrus in the post-surgery group. Compared to the HC, long-term increased activity was still present in the right frontal operculum cortex, right insular cortex, right inferior frontal gyrus (pars opercularis), and right frontal pole despite the effectiveness of MVD surgery. In contrast, MVD significantly reduced the area of aberrant activation regions, particularly in the operculo-insular cortex, and also normalized cerebellar abnormalities.

DISCUSSION: Our study demonstrates that ICA can effectively identify distinct patterns of functional connectivity in the sensorimotor network associated with TN and MVD surgery. These regions are involved in altered pain processing, including nociceptive stimulus integration, subjective pain perception, pain chronification, and pain-related empathy. Our findings suggest promising biomarkers for TN and provide insights for developing targeted treatments.

PMID:40837096 | PMC:PMC12361157 | DOI:10.3389/fphys.2025.1633028