- Team identifies cannabinoid pathway linked to both therapeutic and addictive effects
- Findings point to potential alternative to opioid-based pain treatments
A team from Zhejiang University has designed a new small-molecule drug candidate that retains pain-relieving effects of cannabis while removing key addictive and tolerance-related properties, according to a study published in Cell.
The work, led by professors Li Xiaoming, Dong Xiaowu and Zhang Yan, addresses a long-standing challenge in neuropharmacology: separating the therapeutic effects of cannabinoid-related pathways from the biological mechanisms associated with dependence and adverse psychiatric effects.
Cannabinoid compounds are known to be effective in treating conditions such as chronic pain, anxiety and epilepsy, but their clinical use has been constrained by risks of addiction and other side effects. While previous research had clarified parts of the therapeutic signaling pathway, the mechanisms behind unwanted effects remained unresolved.
The Zhejiang University team said it mapped the three-dimensional structure of a key receptor complex in 2023, providing the basis for what it described as a “selective switch” that could distinguish between beneficial and harmful signaling.
Building on this structural insight, the researchers used molecular design to develop a compound that, in preclinical tests, maintained analgesic activity while showing reduced signs of tolerance and dependence in cell-based and animal studies, as well as improved safety and pharmacokinetic profiles.
The study has progressed to large-animal models, where the compound continued to demonstrate efficacy and safety signals in more complex physiological conditions. The team is now advancing preclinical validation with the aim of moving toward clinical trials.
Researchers said the approach could support development of new non-opioid treatments for pain, as well as potential therapies for mood disorders and depression, though further testing is needed to confirm safety and effectiveness in humans.
