The invention provides four butyrylcholinesterase variants having
increased cocaine hydrolysis activity as well as the corresponding
encoding nucleic acids. The invention also provides libraries comprising
butyrylcholinesterase variants having at least one amino acid alteration
in one or more regions of butyrylcholinesterase and further having at
least one butyrylcholinesterase variant exhibiting enhanced cocaine
hydrolysis activity compared to butyrylcholinesterase. The invention
further provides methods of hydrolyzing a cocaine-based
butyrylcholinesterase substrate as well as methods of treating a
cocaine-induced condition.