Safety and Preliminary Efficacy of the Acetylcholinesterase Inhibitor Huperzine A as a Treatment for Cocaine Use Disorder.

BACKGROUND Cholinergic transmission is altered by drugs of abuse and contributes to psychostimulant reinforcement. In particular, acetylcholinesterase inhibitors, like huperzine A, may be effective as treatments for cocaine use disorder. METHODS The current report describes results from a double-blind, placebo-controlled study in which participants (n=14-17/group) were randomized to huperzine A (0.4 or 0.8 mg) or placebo. Participants received randomized infusions of cocaine (0 and 40 mg, IV) on days 1 and 9. On day 10, participants received noncontingent, randomized infusions of cocaine (0 and 20mg, IV) before making 5 choices to receive additional infusions. RESULTS Huperzine A was safe and well-tolerated and compared with placebo, treatment with huperzine A did not cause significant changes in any cocaine pharmacokinetic parameters (all P>.05). Time-course and peak effects analyses show that treatment with 0.4 mg of huperzine A significantly attenuated cocaine-induced increases of "Any Drug Effect," "High," "Stimulated," "Willing to Pay," and "Bad Effects" (all P>.05). CONCLUSIONS The current study represents a significant contribution to the addiction field since it serves as the first published report on the safety and potential efficacy of huperzine A as a treatment for cocaine use disorder.