A TLR4 agonist for the treatment of cocaine addiction
An FDA approved molecule that could be repurposed to reduce behavioral sensitization to cocaine has been identified at McGill University.
For addictive drugs such as cocaine, the molecular mechanisms underlying behavioral sensitization are not fully understood. Few effective treatments exist for drug addiction and cocaine addiction in particular has no particular options. One area of current interest is inflammatory molecules, such as Tumor necrosis factor alpha (TNF-a) and how they regulate neuronal circuits. While the exact role of inflammation in neural pathways affected by drug addiction is still unclear, recent studies have suggested they affect dopamine receptors and other addiction associated cellular pathways.
This technology is the use of monophosphoryl lipid A (MPLA) to reduce behavioral sensitization to cocaine by moderately increasing TNF-a with Toll-Like Receptor 4 (TLF4) activation. With a mouse model, the inventors were able to show that introduction of MPLA can reduce sensitization after prolonged abstinence from cocaine. This suggests that increasing TNF-a with mild TLF4 activation may help blunt addictive needs over time. With this alteration of sensitization, MPLA could reduce drug-seeking motivation and be used to prevent relapse.
- MPLA can reduce behavioral sensitization after prolonged abstinence from cocaine
- MPLA is an FDA approved component of some vaccine adjuvants and could be repurposed for use in the treatment of cocaine addiction