Effects of THC, CBD, and Their Combination on EEG Dynamics in Rats.

Acute oral administration of THC (10 mg/kg), CBD (10 mg/kg), or their combination in freely moving rats alters resting-state EEG dynamics. THC and THC+CBD produced the strongest and most spatially extensive increases in low-frequency spectral power, with significant delta-beta clusters in prefrontal, cingulate, hippocampal, and striatal regions. CBD yielded fewer and smaller clusters. Connectivity analyses revealed altered functional coupling within overlapping CB1 receptor-rich regions. The combination treatment closely resembled THC alone, suggesting a dominant THC-driven contribution. These findings identify a cannabinoid-specific EEG signature of enhanced low-frequency oscillatory activity and altered large-scale network organization.

Study at a glance

Abstract

Cannabinoids modulate brain network activity, yet the spatial organization and temporal evolution of their electrophysiological effects remain insufficiently characterized in animal models. Here, we investigated how acute oral administration of ?9-tetrahydrocannabinol (THC; 10 mg/kg), cannabidiol (CBD; 10 mg/kg), and their combination influences resting-state EEG dynamics in freely moving rats. Adult male Wistar rats implanted with a 12-electrode epidural array received one of the treatments via intragastric gavage. EEG was recorded during baseline and three post-administration intervals (80-90, 110-120, 140-150 min) and analyzed using spectral decomposition, source localization, and functional connectivity within an anatomically realistic rat head model. Cannabinoid administration increased low-frequency spectral power, with source-space statistics identifying significant delta-beta clusters (p < 0.05, FDR-corrected), most prominently in prefrontal, cingulate, hippocampal, and striatal regions. THC and THC+CBD produced the strongest and most spatially extensive significant effects, whereas CBD yielded fewer and smaller clusters. Connectivity analyses demonstrated convergent treatment-related changes, revealing significant alterations in functional coupling within overlapping regions rich in CB1 receptors. These connectivity effects mirrored the spatial distribution of source-power findings, indicating that cannabinoids influence not only local oscillatory activity but also large-scale network organization. Across analyses, the combination treatment closely resembled the THC profile, suggesting a dominant THC-driven contribution with CBD exerting weaker, directionally similar modulation. Together, these findings identify a robust cannabinoid-specific EEG signature characterized by enhanced low-frequency oscillatory activity, altered functional connectivity, and regionally selective engagement of CB1-rich cortical and limbic structures.