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.