Cannabidiol Does Not Impair Anabolic Signaling Following Eccentric Contractions in Rats

Abstract

Cannabidiol (CBD) has proven clinical benefits in the treatment of seizures, inflammation, and pain. The recent legalization of
CBD in many countries has caused increased interest in the drug as an over-the-counter treatment for athletes looking to improve
recovery. However, no data on the effects of CBD on the adaptive response to exercise in muscle are available. To address this
gap, we eccentrically loaded the tibialis anterior muscle of 14 rats, injected them with a vehicle (n = 7) or 100 mg/kg CBD (n = 7),
and measured markers of injury, inflammation, anabolic signaling, and autophagy 18 hr later. Pro-inflammatory signaling
through nuclear factor kappa B (NF-kB) (Ser536) increased with loading in both groups; however, the effect was significantly
greater (36%) in the vehicle group (p < .05). Simultaneously, anabolic signaling through ribosomal protein S6 kinase beta-1
(S6K1) (Thr389) increased after eccentric contractions in both groups with no difference between vehicle and CBD (p = .66). The
ribosomal protein S6 phosphorylation (240/244) increased with stimulation (p < .001) and tended to be higher in the CBD group
(p = .09). The ubiquitin-binding protein p62 levels were not modulated by stimulation (p = .6), but they were 46% greater in the
CBD compared with the vehicle group (p = .01). Although liver weight did not differ between the groups (p = .99) and levels of
proteins associated with stress were similar, we did observe serious side effects in one animal. In conclusion, an acute dose of
CBD decreased pro-inflammatory signaling in the tibialis anterior without blunting the anabolic response to exercise in rats.
Future research should determine whether these effects translate to improved recovery without altering adaptation in humans.