The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model

Abstract

In the present study, cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), and combinations of CBD and THC, were evaluated in the mouse maximal electroshock (MES) seizure test - an animal model of generalized-onset seizures. Male CF-1 mice were injected intraperitoneally (i.p.) with either CBD, THC or a combination of CBD and THC. The MES test was conducted 2 h after the injection of CBD and 1 h after the injection of THC. A wide range of doses was tested to allow the construction of dose-response curves. Toxicity was assessed using a behavioral rating scale. It was found that: 1) the ED₅₀ for THC alone was 52 mg/kg and its therapeutic index (TI) was 1.7; 2) the ED₅₀ for CBD alone was 190 mg/kg and its TI was 2.4; and 3) the ED₅₀ for a 15:1 combination of CBD+THC was 130 mg/kg + 8.6 mg/kg (CBD + THC). Thus, CBD and THC were both effective in the MES model, and CBD was somewhat more effective in the presence of low (non-therapeutic) doses of THC. The improvement in CBD's effect, however, was less dramatic than that seen in past experiments with the amygdala-kindling model (Fallah et al., 2021). Both CBD alone and CBD+THC in combination might be useful in the treatment of generalized-onset seizures. The advantage of adding THC to CBD, however, might be less than in the treatment of focal-onset seizures.

Keywords: Cannabidiol; Cannabis; Entourage; Epilepsy; Maximal electroshock seizures; Tetrahydrocannabinol.