Increased brain metabolism after acute administration of the synthetic cannabinoid HU210: A small animal PET imaging study with 18F-FDG

Cannabis use has been shown to alter brain metabolism in both rat models and humans although the observations between both species are conflicting. In the present study, we examined the short term effects of a single-dose injection of the synthetic cannabinoid agonist HU210 on glucose metabolism in the rat brain using small animal 18F-2-fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) 15 min (Day 1) and 24 h (Day 2) post-injection of the agonist in the same animal. Young adult male Wistar rats received an intra-peritoneal injection of HU210 (100 μg/kg, n = 7) or vehicle (n = 5) on Day 1. Approximately 1 mCi of 18F-FDG was injected intravenously into each animal at 15 min (Day 1) and 24 h (Day 2) post-injection of HU210. A 5-min Computer Tomography (CT) scan followed by a 20-min PET scan was performed 40 min after each 18F-FDG injection. Standardised Uptake Values (SUVs) were calculated for 10 brain regions of interest (ROIs). Global increased SUVs in the whole brain, hence global brain metabolism, were observed following HU210 treatment on Day 1 compared to the controls (21%, P < 0.0001), but not in individual brain regions. On Day 2, however, no statistically significant differences were observed between the treated and control groups. At the 24 h time point (Day 2), SUVs in the HU210 treated group returned to control levels (21–30% decrease compared to Day 1), in all ROIs investigated (P < 0.0001). In the control group, SUVs did not differ between the two acquisition days in all brain regions. The present results suggest that high-dose HU210 increases brain glucose metabolism in the rat brain shortly after administration, in line with normalised human in vivo studies, an effect that was no longer apparent 24 h later.

► The present study demonstrates the acute (Day 1) and later (Day 2) effects of the cannabinoid agonist, HU210 on the brain glucose metabolism after its high, single dose administration over a period of 24 h post-injection of the agonist in rats.
► Acute HU210 exposure caused an increase in SUVs in the whole brain reflecting whole brain hypermetabolism, an effect that is attenuated 24 h later.
► The study also hypothesises the possible mechanisms for these observed effects on Day 1 (brain glucose hypermetabolism) and Day 2 (the attenuation of this hypermetabolism).