title: Subjective and Cardiovascular Effects of Intravenous Methamphetamine during Perindopril Maintenance: A Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study.
abstract: Our pilot study suggested that the angiotensin-converting enzyme inhibitor perindopril might reduce some subjective effects produced by i.v. methamphetamine. We characterized the impact of a wider range of perindopril doses on methamphetamine-induced effects in a larger group of non-treatment-seeking, methamphetamine-using volunteers.
  
  
  
  Before treatment, participants received 30mg methamphetamine. After 5 to 7 days of perindopril treatment (0, 4, 8, or 16mg/d), participants received 15 and 30mg of methamphetamine on alternate days. Before and after treatment, participants rated subjective effects and cardiovascular measures were collected.
  
  
  
  Prior to treatment with perindopril, there were no significant differences between treatment groups on maximum or peak subjective ratings or on peak cardiovascular effects. Following perindopril treatment, there were significant main effects of treatment on peak subjective ratings of "anxious" and "stimulated"; compared to placebo treatment, treatment with 8mg perindopril significantly reduced peak ratings of both anxious (P=.0009) and stimulated (P=.0070). There were no significant posttreatment differences between groups on peak cardiovascular effects.
  
  
  
  Moderate doses of perindopril (8mg) significantly reduced peak subjective ratings of anxious and stimulated as well as attenuated many other subjective effects produced by methamphetamine, likely by inhibiting angiotensin II synthesis. Angiotensin II is known to facilitate the effects of norepinephrine, which contributes to methamphetamine's subjective effects. The lack of a classic dose-response function likely results from either nonspecific effects of perindopril or from between-group differences that were not accounted for in the current study (i.e., genetic variations and/or caffeine use). The current findings suggest that while angiotensin-converting enzyme inhibitors can reduce some effects produced by methamphetamine, more consistent treatment effects might be achieved by targeting components of the renin-angiotensin system that are downstream of angiotensin-converting enzyme.
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences (Drs Verrico, Haile, De La Garza, Kosten, and Newton), Department of Pharmacology (Drs Verrico, De La Garza, Kosten, and Newton), and Department of Neuroscience (Drs De La Garza and Kosten), Baylor College of Medicine, Houston, TX; Department of Veterans Affairs Medical Center, Kansas City, Missouri (Dr Grasing); University of Kansas School of Medicine, Kansas City, Missouri (Dr Grasing). verrico@bcm.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Verrico
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences (Drs Verrico, Haile, De La Garza, Kosten, and Newton), Department of Pharmacology (Drs Verrico, De La Garza, Kosten, and Newton), and Department of Neuroscience (Drs De La Garza and Kosten), Baylor College of Medicine, Houston, TX; Department of Veterans Affairs Medical Center, Kansas City, Missouri (Dr Grasing); University of Kansas School of Medicine, Kansas City, Missouri (Dr Grasing).
authors.forename: Colin N
authors.initials: CN
authors.lastname: Haile
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences (Drs Verrico, Haile, De La Garza, Kosten, and Newton), Department of Pharmacology (Drs Verrico, De La Garza, Kosten, and Newton), and Department of Neuroscience (Drs De La Garza and Kosten), Baylor College of Medicine, Houston, TX; Department of Veterans Affairs Medical Center, Kansas City, Missouri (Dr Grasing); University of Kansas School of Medicine, Kansas City, Missouri (Dr Grasing).
authors.forename: Richard
authors.initials: R
authors.lastname: De La Garza
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences (Drs Verrico, Haile, De La Garza, Kosten, and Newton), Department of Pharmacology (Drs Verrico, De La Garza, Kosten, and Newton), and Department of Neuroscience (Drs De La Garza and Kosten), Baylor College of Medicine, Houston, TX; Department of Veterans Affairs Medical Center, Kansas City, Missouri (Dr Grasing); University of Kansas School of Medicine, Kansas City, Missouri (Dr Grasing).
authors.forename: Kenneth
authors.initials: K
authors.lastname: Grasing
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences (Drs Verrico, Haile, De La Garza, Kosten, and Newton), Department of Pharmacology (Drs Verrico, De La Garza, Kosten, and Newton), and Department of Neuroscience (Drs De La Garza and Kosten), Baylor College of Medicine, Houston, TX; Department of Veterans Affairs Medical Center, Kansas City, Missouri (Dr Grasing); University of Kansas School of Medicine, Kansas City, Missouri (Dr Grasing).
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences (Drs Verrico, Haile, De La Garza, Kosten, and Newton), Department of Pharmacology (Drs Verrico, De La Garza, Kosten, and Newton), and Department of Neuroscience (Drs De La Garza and Kosten), Baylor College of Medicine, Houston, TX; Department of Veterans Affairs Medical Center, Kansas City, Missouri (Dr Grasing); University of Kansas School of Medicine, Kansas City, Missouri (Dr Grasing).
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Newton
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D055030:Drug Users / Q000523:psychology; D005260:Female; D064368:Healthy Volunteers / Q000523:psychology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008875:Middle Aged; D020913:Perindopril / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D020913:Perindopril
keywords: human laboratory study; methamphetamine; renin-angiotensin system