New CBD analogue shows promising pain-relieving effects in mice

In addition to being highly addictive, numerous studies suggest that prescription opioids do not effectively control pain in the long term, and researchers have therefore explored various alternatives, including cannabidiol (CBD). CBD is a non-psychoactive substance derived from the cannabis plant.

Studies have shown that while CBD reduces the sensation of pain in animals, its ability to do so in humans is limited by poor bioavailability, the extent to which the drug successfully reaches its site of action. Today, new work from scientists at the Lewis Katz School of Medicine at Temple University suggests that this hurdle could be overcome by a new CBD analogue known as KLS-13019.

“In a mouse model of chemotherapy-induced peripheral neuropathy (CIPN), we were able to show for the first time that KLS-13019 works as well, if not better, than CBD in preventing the development of neuropathy and reversing pain. . sensitivity after pain has been established, ”said Sara Jane Ward, PhD, assistant professor of pharmacology at the Katz School of Medicine and principal investigator of the new study. The results were published online April 6 in the British Journal of Pharmacology.

KLS-13019, developed by Pennsylvania-based bio-pharmaceutical and phyto-medical company Neuropathix, Inc., is among the most promising neuroprotective CBD analogs currently under investigation. In previous work on cell models, it was found to be more potent than CBD, and animal studies suggested it had improved bioavailability.

Encouraged by these initial studies, Dr Ward and colleagues sought to better understand the pain-relieving abilities of KLS-13019, compared to CBD, in animals with CIPN. NHIC is a common side effect of some cancer treatments that damage peripheral nerves, which carry sensory information to the arms, legs and brain. The severe pain, or peripheral neuropathy, caused by ICNP manifests itself in different ways in human patients, but frequently involves tingling or burning sensations and numbness, weakness, or discomfort in the limbs.

In a series of experiments designed to assess animal pain responses, researchers found that pain sensitivity was significantly reduced in animals with CIPN treated with KLS-13019 or CBD. KLS-13019 further reversed sensitivity to painful stimuli in animals with already established peripheral neuropathy, an effect that was not seen in animals treated with CBD.

Previous studies have also hinted at the possibility that CBD may be able to reduce the need for opioids in patients with opioid use disorders.

“Many patients who use opioids for pain management go into a reinforcement cycle, where each opioid use triggers reward pathways and perceived pain relief, leading to addiction,” Dr. Ward.

Although Dr Ward and colleagues found no evidence to support the role of CBD in reducing the need for opioids, they observed a significant reduction in opioid seeking behavior in animals treated with KLS-13019. .

“This tells us that KLS-13019 has benefits beyond its ability to relieve pain,” Dr. Ward said.

The researchers suspect that while it likely shares a mechanism with CBD for relieving pain, KLS-13019 may have an additional mechanism of action, a mechanism that disrupts the pathways that enhance opioid use.

In future work, Dr. Ward and her team plan to explore the mechanisms by which KLS-13019 exerts its effects, particularly those underlying the drug’s ability to disrupt opioid-seeking behavior. They also plan to test the ability of KLS-13019 to relieve other types of pain, beyond CIPN.

Other researchers who contributed to the study include Jeffery D. Foss, Daniel J. Farkas and Lana M. Huynh, Center for Substance Abuse Research at the Katz School of Medicine, and William A. Kinney and Douglas E Brenneman, Neuropathix, Inc., Pennsylvania Biotechnology Center, Doylestown, PA.

The research was funded in part by National Institutes of Health grant R41 DA044898-01.