title: Pilot safety evaluation of varenicline for the treatment of methamphetamine dependence.
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 α4b2 nAChRs with full agonist properties at α7 nAChRs. Oral varenicline dose was titrated over one week to reach 1 mg twice daily, and then was co-administered with 30 mg methamphetamine, delivered in 10 intravenous (iv) 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.
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Zorick
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Rajkumar J
authors.initials: RJ
authors.lastname: Sevak
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Miotto
authors.affiliation: Family Medicine, University of California Los Angeles, Los Angeles, CA, USA; The Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Shoptaw
authors.affiliation: Family Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Aimee-Noelle
authors.initials: AN
authors.lastname: Swanson
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Clayton
authors.initials: C
authors.lastname: Clement
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: De La Garza
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Newton
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA; Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; The Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
keywords: acetylcholine; methamphetamine; nicotinic; safety; treatment; varenicline