The effectiveness of certain anesthetics depends in part on their lipid solubility. Why is this? Lipid-soluble drugs trigger the opening of certain channels, which they can use to pass through the plasma membrane. The hydrophilic nature of lipid-soluble drugs speeds up their passage through the plasma membrane. The hydrophobic core of the phospholipid bilayer enables lipid-soluble substances to readily pass through the plasma membrane. Polar substances, such as lipid-soluble drugs, have high solubility.