Molecular dynamics simulations of CBD and THC with a DPPC / DPPG monolayer membrane: Comparative study with morphine and lidocaine

In recent years, the discussion about using marijuana to treat some specific diseases has been the reason for several studies to determine how Cannabis could affect or benefit the human body, such as chronic pain. However, the legal status of marijuana in different parts of the world remains a problem when conducting experiments for academic purposes. In this way, algorithms based on molecular dynamics are of great help to study the change in the physical properties of membranes, which is our first defense barrier, in the presence of external agents. Here we used equilibrium molecular dynamics to study the interactions of a DPPC/DPPG monolayer membrane with CBD and THC, these two molecules being one of the main components of Cannabis, and compare the interactions with morphine and lidocaine which are drugs with well-known anesthetic properties. We also used the umbrella sampling method to determine the variations of the potential of mean forces as every single drug crosses the membrane obtaining an approximation of the hydration free energy, we obtained a value of 57 kJ mol-1 for CBD and 5 kJ mol-1 for THC; values reported for the first time using molecular dynamics.