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

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

Br J Pharmacol. 2021 Apr 6. doi: 10.1111/bph.15486. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Cannabidiol (CBD) is a non-euphorigenic component of Cannabis sativa which 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 goal of the present study was to characterize the behavioral pharmacological effects of KLS-13019 in comparison 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 IP or oral administration of CBD, KLS-13019, or morphine. Antinociceptive activity using acetic acid-induced stretching and hot plate, anti-reinforcing effects on palatable food or morphine self-administration, and binding to human opioid receptors were also determined.

KEY RESULTS: Like CBD, IP or oral 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 also 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.

CONCLUSION: KLS-13019 shares CBD’s ability to prevent the development of CIPN, while KLS-13019 uniquely attenuated established CIPN. Because KLS-13019 binds to fewer biological targets, these findings can bring us closer to identifying molecular mechanisms shared by the two compounds as well as those unique to KLS-13019. Lastly, KLS-13019 may possess the ability to attenuate reinforced behavior, an effect not observed in the present study with CBD.

PMID:33822373 | DOI:10.1111/bph.15486

#CBD #Hemp https://pubmed.ncbi.nlm.nih.gov/33822373/?utm_source=Chrome&utm_medium=rss&utm_campaign=None&utm_content=1jYCQzi_o_qLYr-oQfnMhShgOXkvGma3vcnBGJtrBhuJMOvEVJ&fc=None&ff=20210407032711&v=2.14.3 April 6, 2021 10:00 am