title: Effects of acute topiramate dosing on methamphetamine-induced subjective mood.
abstract: Clinical studies have shown that topiramate, a sulphamate-substituted fructopyranose derivative, might be an efficacious treatment for alcohol dependence, smoking cessation within an alcohol-dependent population, and cocaine dependence. Mechanistically, topiramate's therapeutic effects have been hypothesized to be due to inhibition of cortico-mesolimbic dopamine function, the primary substrate that governs the acquisition, maintenance, and reinstatement of goal-directed behaviour towards seeking abused drugs. Predicated on this hypothesis, we tested in 10 methamphetamine-dependent individuals (three females) whether low- or high-dose (15 or 30 mg i.v.) methamphetamine-induced positive subjective effects and reinforcement can be antagonized by low- or high-dose (100 or 200 mg orally) topiramate using a placebo-controlled, cross-over, factorial design. Methamphetamine administration was associated with orderly, prototypical, and significant increases on measures of stimulation, euphoria, craving, and reinforcement; however, some dysphoric symptoms also emerged. Topiramate alone showed a non-significant trend towards mild reductions in positive mood and reinforcement; yet topiramate appeared to accentuate the appreciation of methamphetamine-induced stimulation and euphoria significantly, but not craving or reinforcement. The experimental combination of topiramate and methamphetamine appeared to be safe and well tolerated, with few adverse events. Acute dosing with up to 200 mg topiramate appears to enhance, rather than attenuate, the positive subjective effects of methamphetamine. Perhaps this indicates a partial inhibition of methamphetamine's reinforcing effects. Thus, testing chronically administered or higher doses, or both, of topiramate would be necessary to determine conclusively whether or not it can attenuate the positive subjective and reinforcing effects of methamphetamine.
authors.affiliation: Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: John D
authors.initials: JD
authors.lastname: Roache
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Lynda T
authors.initials: LT
authors.lastname: Wells
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wallace
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dawes
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Xin-Qun
authors.initials: XQ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology*; D016739:Behavior, Addictive; D000697:Central Nervous System Stimulants / Q000009:adverse effects; D018592:Cross-Over Studies; D015259:Dopamine Agents / Q000009:adverse effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D012054:Reinforcement, Psychology; D011795:Surveys and Questionnaires; D000077236:Topiramate
chemical_list: D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D000077236:Topiramate; D005632:Fructose; D008694:Methamphetamine