Researchers have developed a compound that mimics the pain-relieving effects of a molecule found in the cannabis plant without causing addiction or psychoactive side effects in mice. The corresponding study was published in Nature.
“For millennia, people have turned to marijuana as a treatment for pain,” co-corresponding author Robert W. Gereau, PhD, Professor of Anesthesiology at Washington University School of Medicine, said in a press release.
“Clinical trials also have evaluated whether cannabis provides long-term pain relief. But inevitably the psychoactive side effects of cannabis have been problematic, preventing cannabis from being considered as a viable treatment option for pain. However, we were able to overcome that issue,” he added.
In the current study, researchers developed a cannabinoid molecule with a positive charge, disabling it from crossing the blood-brain barrier while allowing it to engage CB1 receptors elsewhere in the body. By ensuring the molecule would only bind to nerve cells outside of the brain, the researchers were able to achieve pain relief without side effects like psychoactive states and addiction.
During its development, the researchers found a hidden pocket on the CB1 receptor with the potential to act as an additional binding site. Considered inaccessible to cannabinoids, the researchers found that the pocket opens for short periods of time, something which could allow their modified cannabinoid compound to bind and minimize tolerance.
Once developed, the researchers tested the compound's effects in mouse models of nerve-injury pain and migraine headaches, where it demonstrated prolonged pain relief. The mice also showed no signs of tolerance despite twice-daily treatments for nine days.
“These results show how targeting a cryptic pocket in a G-protein-coupled receptor can lead to enhanced peripheral selectivity, biased signalling, desired in vivo pharmacology and reduced adverse effects. This has substantial implications for chronic pain treatment but could also revolutionize the design of drugs targeting other G-protein-coupled receptors,” wrote the researchers in their paper.
The researchers now intend to develop the compound into an oral drug for study in clinical trials.
Sources: EurekAlert, Nature