Analogs Of Marijuana Active Ingredient May Have More Predictable Therapeutic Properties

Cannabis may be a treatment for glaucoma, pain, and other ailments, but the strength and duration of action for a dose of medical marijuana can be unpredictable, to say nothing of the psychotropic effects. Researchers are trying to remedy the consistency challenges by developing cannabinoids with controllable deactivation. This strategy has worked for several drug classes, including anesthetics, but attempts to make short-acting cannabinoids have led to compounds with poor binding affinity to cannabinoid receptors. Now, a team led by Alexandros Makriyannis of Northeastern University has overcome that problem. The team replaced one of the three rings in (–)-Δ⁹-tetrahydrocannabinol (THC), the active ingredient in marijuana, with a seven-membered lactone ring (ACS Med. Chem. Lett. 2014, DOI: 10.1021/ml4005304). One of the new cannabinoids, AM4809, binds to the rat CB1 cannabinoid receptor with 4.6 nM affinity, about eight times as tight as THC binds. It has a half-life of 15.1 minutes in vitro, far shorter than the average for THC. Makriyannis notes that his team has developed other analogs with controllable half-lives (J. Med. Chem. 2013, DOI: 10.1021/jm4016075). A patent covering a variety of these compounds has been filed and licensed to MAKScientific, a company founded by Makriyannis.