Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study.
Eilidh Macnicol, Michelle Kokkinou, Maria Elisa Serrano Navacerrada, Donna-michelle Smith, Jennifer Li, Camilla Simmons, Eugene Kim, Michel Mesquita, Loreto Rojo Gonzalez, Tierney Andrews, Sally Loomis, Royston A Gray, Volker Knappertz, Benjamin J Whalley, Andrew C Mccreary, Steven Cr Williams, David Virley, Diana Cash
Journal of psychopharmacology (Oxford, England) March 1, 2026 Peer reviewed DOI: 10.1177/02698811251360745 via PubMed
Summary
THC increases brain connectivity and blood flow in rats, while CBD decreases connectivity without affecting blood flow. Combining THC and CBD produces moderate increases in both measures. The study used multimodal neuroimaging to assess functional connectivity and cerebral blood flow in adult male Sprague Dawley rats after administration of THC (10 mg/kg), CBD (150 mg/kg), a combination (10.8:10 mg/kg THC:CBD), or vehicle. THC elevated whole-brain connectivity and clustering coefficient, with increased blood flow in cortical and subcortical regions. CBD reduced connectivity metrics without altering blood flow. The combination attenuated THC-driven increases in cortical-hippocampal and cortical-striatal connectivity.
Study at a glance
| Design | preclinical experimental study |
|---|---|
| Population | adult male Sprague Dawley rats |
| Key finding | THC increases brain functional connectivity and cerebral blood flow in rats, while CBD decreases connectivity without affecting blood flow, and their combination produces moderate increases moderated by CBD. |
Abstract
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. This study evaluated the effects of THC, CBD, and their combination on brain functional connectivity (FC) and cerebral blood flow (CBF) using multimodal neuroimaging. 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. 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. 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.