Effects of tetrahydrocannabinol on glucose uptake in the rat brain

Δ⁹-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [¹⁸F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of < 1 ng/ml (injected dose: ≤ 0.01 mg/kg) corresponded to an increased glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies.