The cardiovascular and subjective effects of methamphetamine combined with gamma-vinyl-gamma-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers.

TitleThe cardiovascular and subjective effects of methamphetamine combined with gamma-vinyl-gamma-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers.
Publication TypeJournal Article
Year of Publication2009
AuthorsDe La Garza, R, Zorick T, Heinzerling KG, Nusinowitz S, London ED, Shoptaw S, Moody DE, Newton TF
JournalPharmacology, biochemistry, and behavior
Volume94
Issue1
Pagination186-93
Date Published2009 Nov
ISSN1873-5177
Keywords4-Aminobutyrate Transaminase, Adult, Amphetamine-Related Disorders, Blood Pressure, Cardiovascular System, Central Nervous System Stimulants, Depression, Double-Blind Method, Female, GABA Agents, Half-Life, Heart Rate, Humans, Male, Methamphetamine, Middle Aged, Reinforcement (Psychology), Vigabatrin, Visual Fields
Abstract

Gamma-vinyl-gamma-aminobutyric acid (GVG) elevates central nervous system gamma-aminobutyric acid (GABA) levels by irreversibly inhibiting GABA transaminase. An open-label clinical trial in humans suggested that GVG may reduce cocaine and methamphetamine use. To test safety and to obtain preliminary data on efficacy of GVG for treating methamphetamine dependence, we conducted a double-blind, placebo-controlled, parallel group study of GVG interaction with the cardiovascular and subjective effects produced by methamphetamine. Non-treatment seeking methamphetamine-dependent volunteers received either GVG (N=8) or placebo (N=9) by random assignment. GVG treatment was initiated at 1 g/day and increased to 5 g/day. After reaching the target dose of 5 g/day, participants received methamphetamine (15+30 mg, IV), and cardiovascular and subjective effects were assessed. No serious adverse events were noted, and the total number of adverse events was similar between the treatment groups. Considering the full time course and peak effects independently, no significant differences were detected between the groups for systolic or diastolic blood pressures, or heart rate, following methamphetamine exposure. Some methamphetamine-induced cardiovascular changes approached significance (p<0.10) and may warrant attention in future trials. Methamphetamine-induced subjective effects ("any drug effect", "high", "crave methamphetamine") were statistically similar between GVG and placebo treatment groups. Pharmacokinetic data indicate that GVG treatment did not alter methamphetamine or amphetamine plasma levels, and there was no association between methamphetamine or amphetamine plasma levels and peak cardiovascular effects. Taken together, the data indicate that GVG treatment is generally well tolerated but not efficacious in attenuating the positive subjective effects of methamphetamine in the laboratory.

DOI10.1001/archgenpsychiatry.2011.51
Alternate JournalPharmacol. Biochem. Behav.