The International Journal of Neuropsychopharmacology

Research Article

Safety and efficacy of varenicline to reduce positive subjective effects produced by methamphetamine in methamphetamine-dependent volunteers

Christopher D. Verricoa1 c1, James J. Mahoney IIIa1, Daisy G. Y. Thompson-Lakea1, Ryan S. Bennetta1, Thomas F. Newtona1 and Richard De La Garza IIa1

a1 Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA


Methamphetamine use is increasing in the US. Although there are no Food and Drug Administration (FDA)-approved medications for methamphetamine dependence, preclinical and clinical studies suggest that methamphetamine users may benefit from treatments that enhance cholinergic neurotransmission. Consequently, we determined the safety and the efficacy of varenicline treatment, a partial agonist at α4β2 and a full agonist at α7 nicotinic acetylcholine receptors, to reduce positive subjective effects produced by smoked methamphetamine. Additionally, the effects of treatment with varenicline on the cardiovascular and reinforcing effects of methamphetamine were determined. We conducted a double-blind, placebo-controlled, within-subjects trial of varenicline vs. placebo in methamphetamine-dependent volunteers who were not seeking treatment. Participants were randomly assigned to receive one dose of varenicline (0, 1, or 2 mg) po BID, titrated up to the target dose over days 1–7, during each of three separate inpatient phases. Safety measures included the frequency, duration, severity, and relatedness of adverse events reported. Positive subjective effects included ‘Any drug effect’, ‘High’, ‘Good effects’, ‘Stimulated’, and ‘Drug liking’, which were rated by participants before and for 1 h after smoking methamphetamine (0, 10, and 30 mg). There were no serious adverse events and no differences in adverse events reported during the three phases. Varenicline (2 mg) significantly reduced ratings of ‘Any drug effect’ and ‘Stimulated’, as well as attenuated ratings of ‘High’, ‘Drug liking’, and ‘Good effects’, produced by methamphetamine (30 mg). The ability of varenicline to attenuate the positive subjective effects of methamphetamine in the laboratory suggests that varenicline should continue to be explored as a treatment for methamphetamine dependence.

(Received June 27 2013)

(Reviewed July 16 2013)

(Revised September 18 2013)

(Accepted October 16 2013)

Key words

  • Acetylcholine;
  • addiction;
  • methamphetamine;
  • varenicline


c1 Address for correspondence: C. D. Verrico, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 1977 Butler Blvd. Suite E4.163, Houston, Texas 77030, USA. Tel.: (713) 791-1414 x6849 Fax: (713) 794-7833 Email: