The use of zonal ultracentrifugation in the investigation of the binding of delta9-tetrahydrocannabinol by plasma lipoproteins.

The major classes of lipoprotein, very low density, low density, and high density, as well as the lipoprotein-free protein were isolated from plasma by rate-zonal centrifugation. Fractionation of plasma after the addition of delta9-tetrahydrocannabinol (THC) showed that over 60% of the drug is associated with the lipoprotein; the remainder of the drug appears to be bound by albumin. In human plasma the low density lipoprotein is the major lipoprotein; in rat plasma the very low density and high density lipoproteins predominate. The distribution of THC in the lipoprotein reflected this species difference. In both species the distribution of THC among the lipoproteins appears to be related to their content of neutral lipid or total lipid rather than that of phospholipid or protein. Fractionation of plasma after the addition of estradiol, imipramine, prostaglandin E2, digitoxin, or dicumarol demonstrated that the lipoproteins contribute little to their binding. Thus, even among lipid-soluble compounds, the binding of THC in plasma is unusual.