title: Altering cortisol level does not change the pleasurable effects of methamphetamine in humans.
abstract: Preclinical studies have linked corticosteroid secretion and levels with drug self-administration by animals. In a double-blind, cross-over study, subjective, physiological, and endocrine responses to intravenous doses of methamphetamine 0.5 mg/kg or placebo were assessed in eight methamphetamine-experienced subjects after three cortisol-modifying premedication conditions: augmenting cortisol level with oral hydrocortisone 50 mg, blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone 1500 mg orally, or no premedication. Although the pharmacologic manipulations produced the expected hormonal changes, subjective response to the methamphetamine showed few differences. Diminishing cortisol response by pharmacologic blockade did not alter the pleasurable effects of methamphetamine. Hydrocortisone did increase self-reported 'bad drug effect' and decreased craving after saline placebo relative to the period following methamphetamine. Metyrapone was associated with significant premature ventricular complexes in two subjects during methamphetamine administration and may not be safe for those who use methamphetamine.
authors.affiliation: Drug Dependence Research Center, Langley Porter Psychiatric Institute, Department of Psychiatry, University of California, San Francisco, CA 94143-0984, USA. dharris@itsa.ucsf.edu
authors.forename: Debra S
authors.initials: DS
authors.lastname: Harris
authors.forename: Victor I
authors.initials: VI
authors.lastname: Reus
authors.forename: Owen M
authors.initials: OM
authors.lastname: Wolkowitz
authors.forename: John E
authors.initials: JE
authors.lastname: Mendelson
authors.forename: Reese T
authors.initials: RT
authors.lastname: Jones
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood* / Q000652:urine; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D008797:Metyrapone / Q000008:administration & dosage / Q000652:urine; D012119:Respiration / Q000187:drug effects; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D003900:Desoxycorticosterone; D008694:Methamphetamine; D003687:Dehydroepiandrosterone; D006854:Hydrocortisone; D008797:Metyrapone