Behavioural and pharmacological effects of cannabidiol (CBD) and the cannabidiol analogue KLS‐13019 in mouse models of pain and reinforcement

Authors:
Publisher website
Google Scholar
Abstract
Background and Purpose: Cannabidiol (CBD) is a non‐euphorigenic component of Cannabis sativa that prevents the development of paclitaxel‐induced mechanical sensitivity in a mouse model of chemotherapy‐induced peripheral neuropathy (CIPN). We recently reported that the CBD structural analogue KLS‐13019 shows efficacy in an in vitro model of CIPN. The present study was to characterize the behavioural effects of KLS‐13019 compared to CBD and morphine in mouse models of CIPN, nociceptive pain and reinforcement.Experimental Approach: Prevention or reversal of paclitaxel‐induced mechanical sensitivity were assessed following intraperitoneal or oral administration of CBD, KLS‐13019 or morphine. Antinociceptive activity using acetic acid‐induced stretching and hot plate assay, anti‐reinforcing effects on palatable food or morphine self‐administration and binding to human opioid receptors were also determined.Key Results: Like CBD, KLS‐13019 prevented the development of mechanical sensitivity associated with paclitaxel administration. In contrast to CBD, KLS‐13019 was also effective at reversing established mechanical sensitivity. KLS‐13019 significantly attenuated acetic acid‐induced stretching and produced modest effects in the hot plate assay. KLS‐13019 was devoid of activity at μ‐, δ‐ or κ‐opioid receptors. Lastly, KLS‐13019, but not CBD, attenuated the reinforcing effects of palatable food or morphine.Conclusions and Implications: KLS‐13019 like CBD, prevented the development of CIPN, while KLS‐13019 uniquely attenuated established CIPN. Because KLS‐13019 binds to fewer biological targets, this will help to identifying molecular mechanisms shared by these two compounds and those unique to KLS‐13019. Lastly, KLS‐13019 may possess the ability to attenuate reinforced behaviour, an effect not observed in the present study with CBD.
Funding Information
  • National Institutes of Health (R41 DA044898‐01)

This publication has 30 references indexed in Scilit: