Computational Modeling, Design and Synthesis of Selective Cannabinoid Receptor 2 (CB2) Agonists

Abstract

Synthetic cannabinoids that are synthesized and used recreationally are a world-wide health problem. They are synthesized in order to mimic the euphoric effects similar to THC, but due to the higher affinity at the cannabinoid receptors and the unknown mechanism of action, they often cause more severe side effects or even death. Unfortunately, the wide array of starting materials, it is easy to design and synthesize newer synthetic cannabinoids as soon as one is banned. In order to prohibit the use of these designer drugs, they need to be structurally identified. The use of analytical methods such as GC-MS and GC-IR can help with the identification of the synthetic cannabinoids and their respective regioisomers. However, synthetic cannabinoids can also be used therapeutically. Specifically, CB2 selective agonists have become an interesting therapeutic target. Targeting CB2 instead of CB1 is favorable because modulation of CB2 does not elicit unwanted psychotropic effects that are seen with CB1. Designing selective CB2 agonists was more challenging without the publication of the CB2 X-Ray crystal structure. The use of molecular modeling to design a homology model of CB2 in order to design and develop selective CB2 agonists that will be synthesized for therapeutic use is the main goal of this project.