Novel THC Analogues Hold Promise for the Development of Safer, More Effective Cannabinoid Medications
March 26, 2014
Modulation of cannabinoid receptors CB1 and CB2 by tetrahydrocannabinol (THC) and related compounds holds promise for the treatment of conditions including pain, neurodegenerative diseases, inflammation, glaucoma, and eating disorders. However, development of medications based on THC has thus far been limited by several factors including its potential for abuse, its limited bioavailability, and its unpredictable time course of action in the body. One problem is that THC breaks down in the body into metabolites with their own powerful psychoactive effects due to their affinity for the CB1 receptor. To better exploit the therapeutic potential of cannabinoids, a team of researchers at Northeastern University has reported the creation of several new THC analogue molecules that not only are potent activators of CB receptors but also degrade in a more controllable manner in the body and do not produce psychoactive metabolites. The researchers used a “soft-drug” approach that incorporates a feature (in this case, an ester group at the THC molecule’s 2’ position) that causes the molecule to break down into inactive compounds after the desired biological effects have been achieved. The researchers subsequently reported creating additional THC analogues that replace the THC molecule’s C-ring with a lactone, similarly facilitating controlled breakdown in the body and, in one case, more targeted affinity for the CB1 receptor. Both developments may lead to the development of new cannabinoid medications that more effectively and safely exploit the power of the body’s cannabinoid signaling system.