The angiotensin-converting enzyme inhibitor perindopril treatment alters cardiovascular and subjective effects of methamphetamine in humans

A variety of medications have been assessed for their potential efficacy for the treatment of methamphetamine dependence. We conducted this study in an attempt to evaluate the potential of a novel class of medications, angiotensin-converting enzyme inhibitors, as treatments for methamphetamine dependence. All participants met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, third revision (DSM-IV-TR) criteria for methamphetamine abuse or dependence and were not seeking treatment at the time of study entry. The study was conducted using a double-blind design. Subjects received a baseline series of intravenous (IV) doses of methamphetamine (15 mg and 30 mg) and placebo. Subjects received a second identical series of methamphetamine doses 3 and 5 days after initiation of once-daily oral placebo or perindopril treatment. The dose of perindopril was 2 mg, 4 mg, or 8 mg administered in the morning. Perindopril treatment was tolerated well. There were no main effects of perindopril on methamphetamine-induced changes in cardiovascular or subjective effects. There were significant perindopril*methamphetamine interactions for diastolic blood pressure and for ratings of Any Drug Effect, indicating inverted U dose-effect functions for these indices. (C) 2009 Elsevier Ireland Ltd. All rights reserved.