Titer-dependent antagonism of cocaine following active immunization in rhesus monkeys

Immunization may be a useful pharmacokinetic antagonist therapy for cocaine users. Three rhesus monkeys were immunized with a cocaine: bovine serum al bumin conjugate in alum and later with complete and incomplete Freund's adj uvants. Monkeys developed cocaine-binding antibodies (as measured by enzyme -linked immunosorbent assay) after immunization with alum; greater antibody titers developed after immunization with Freund's adjuvants. The response rate-decreasing effect of cocaine diminished in proportion to antibody tite r; there was no substantial change in the rate-decreasing effect of bupropi on. Plasma cocaine concentrations increased in proportion to antibody titer . Immunizations were well tolerated and had no effect on response rates. Th ese data suggest that the antibody response to a cocaine antigen can produc e a specific pharmacokinetic shift in cocaine distribution sufficient to an tagonize a behavioral effect of the drug, and can do so with minimal side e ffects.