FIGURE 1.

Cannabinoids interact with the lipid membrane and influence the functional properties of ion channels and other integral membrane proteins. Cannabinoids enter the lipid membrane and binds to cannabinoid receptors through lipid membrane (Reggio and Traore, 2000; Barnett-Norris et al., 2005; Makriyannis et al., 2005). In addition, cannabinoids directly affect channel function by changing the biophysical properties of the lipid membrane or binding to a hydrophobic binding site(s) located on the transmembrane regions of ligand-gated ion channels (represented with large dashed red arrow). Cannabinoids, like other lipophilic molecules, partition into the lipid bilayer and alter the biophysical properties of the membrane by reducing membrane electrical resistance, increasing membrane fluidity, changing membrane order, increasing membrane stiffness, increasing membrane elasticity, and changing physicochemical and structural properties of bilayer membranes (represented with thinner diagonal red arrows). Secondly, cannabinoids can bind directly to transmembrane domains of ion channels embedded in the cell membrane (see discussion).