Compound harnesses cannabis' pain-relieving properties without side effects

Cannabis-inspired compounds could treat chronic pain without mind-altering or addictive effects. Researchers developed a custom synthetic cannabinoid-like molecule that targets cannabinoid receptor 1 (CB1) in the body while being designed not to reach the brain, aiming to avoid psychoactive side effects. In mouse models of nerve-injury pain and migraine, injections eliminated touch hypersensitivity used as a pain proxy. The compound also produced prolonged pain relief and, over nine days of twice-daily dosing, the animals showed no signs of developing tolerance. The study links the molecule's selectivity to a “cryptic pocket” on the CB1 receptor found via computational modeling, which reduces cellular activity associated with tolerance compared with a conventional binding site. The researchers plan further development toward an oral drug for eventual clinical trials.