Pilot Safety Evaluation of Varenicline for the Treatment of Methamphetamine Dependence.

TitlePilot Safety Evaluation of Varenicline for the Treatment of Methamphetamine Dependence.
Publication TypeJournal Article
Year of Publication2009
AuthorsZorick, T, Sevak RJ, Miotto K, Shoptaw S, Swanson A-N, Clement C, De La Garza R, Newton TF, London ED
JournalJournal of experimental pharmacology
Volume2010
Issue2
Pagination13-18
Date Published2009 Dec 1
ISSN1179-1454
Abstract

Despite the worldwide extent of methamphetamine dependence, no medication has been shown to effectively treat afflicted individuals. One relatively unexplored approach is modulation of cholinergic system function. Animal research suggests that enhancement of central cholinergic activity, possibly at nicotinic acetylcholine receptors (nAChRs), can reduce methamphetamine-related behaviors. Further, preliminary findings indicate that rivastigmine, a cholinesterase inhibitor, may reduce craving for methamphetamine after administration of the drug in human subjects. We therefore performed a double-blind, placebo-controlled, crossover pilot study of the safety and tolerability of varenicline in eight methamphetamine-dependent research subjects. Varenicline is used clinically to aid smoking cessation, and acts as a partial agonist at α4β2 nAChRs with full agonist properties at α7 nAChRs. Oral varenicline dose was titrated over 1 week to reach 1 mg bid, and then was co-administered with 30 mg methamphetamine, delivered in ten intravenous infusions of 3 mg each. Varenicline was found to be safe in combination with IV methamphetamine, producing no cardiac rhythm disturbances or alterations in vital sign parameters. No adverse neuropsychiatric sequelae were detected either during varenicline titration or following administration of methamphetamine. The results suggest that varenicline warrants further investigation as a potential treatment for methamphetamine dependence.

DOI10.1001/archgenpsychiatry.2011.51
Alternate JournalJ Exp Pharmacol