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Nature Chemical Biology

April 4, 2011

The analgesic effects seen after marijuana use are mediated by the drug’s active component THC binding to the ion channel GlyR, therefore enabling the development of a THC variant that has only analgesic properties, reports a study online in Nature Chemical Biology. The high and psychomotor impairment associated with cannabinoid-based medications limit their further development as pain-relievers, but the modified compounds described in this study may lead to new drugs that minimize those side effects.

Marijuana is both analgesic and psychoactive and both of these effects can be attributed to its active component, THC. The psychoactive effects are known to be mediated by THC binding to the cannabinoid receptor CB1R however the mechanisms involved in the analgesic effects are less well known. Li Zhang and colleagues found that THC binds to transmembrane segments of GlyR and specific hydrogen-bonding interactions occur between THC chemical constituents and the receptor. The team found that removal of the hydroxyl groups of THC led to a compound that no longer activated GlyR. These data allowed them to design THC analogs that activate GlyRs but lack CB1R activity.Author contact:Li Zhang (National Institute of Health, Bethesda, MD, USA)Tel: +1 301 443 3755; E-mail: lzhang@mail.nih.gov

DOI:10.1038/nchemb.552 | Original article

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