Cannabis-mimicking painkiller bypasses brain

A molecule that targets the same receptor as the active ingredient in cannabis could lead scientists to new drugs for chronic pain. Chemists designed the compound , known as VIP36, to bind cannabinoid receptor 1 (CB1) in the body but not in the brain. This design prevents the molecule from having psychoactive side effects. In mouse studies, VIP36 treated inflammatory pain, nerve pain, and migraines ( Nature 2025, DOI: 10.1038/s41586-025-08618-7). Scientists have long sought analgesic compounds that target CB1. But these molecules typically get shuttled to CB1 in the brain instead of to CB1 in the body’s sensory neurons. Many CB1-targeting molecules are also associated with tolerance—needing to take more and more of a compound to achieve the same painkilling effect. “We were trying to understand if you could separate analgesia through peripheral receptors from these other issues of psychoactivity and tolerance,” says Robert W. Gereau IV, a researcher at