This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This will be a double-blind, placebo-controlled, between- subjects study. It will be conducted in 80 non-treatment seeking methamphetamine (MA) dependent subjects who will be resident at the Michael De Bakey VA Medical Center (MEDVAC) for the 8-day duration of the study. After admission to the study and stabilization and initial monitoring, participants will receive 15mg and 30mg MA separated by at least 4 hours. Over the next several days they will undergo testing of cue reactivity and then participate in MA self-administration in which they will have the opportunity to choose between 3mg MA or money alternatives. Participants will then be randomly assigned to placebo (n=20) or perindopril 4mg, 8mg, or 16mg (n=20 for each group) for the remainder of the study. The 15 and 30mg MA dosing, cue reactivity testing, and MA self-administration activities will then be repeated as before. Participants will then be discharged from the study and will return at intervals for payment and assessment of late emerging adverse events. Should there be difficulties securing access to sufficient hospital beds or if weekend nursing coverage becomes problematic, parts of the protocol may be conducted with participants as outpatients. Abstinence from illicit MA use will be ensured by daily urine testing with serial dilution of urine used to separate episodes of illicit use from MA administered as part of this study. Participants will receive payments of $50 per day provided they abstain from illicit MA use regardless of whether they participate as inpatients or outpatients.
Aim 1. To conduct human laboratory research to characterize effects of treatment with perindopril (4mg, 8mg, and 16mg) compared to placebo, on cardiovascular, subjective, and reinforcing effects of MA (9mg and 30mg, IV, compared to saline placebo) in MA-dependent volunteers. Hypothesis 1: Perindopril treatment will dose-dependently attenuate the reinforcing effects of MA. Hypothesis 2: Perindopril treatment will dose-dependently attenuate MA-induced elevations in craving. Primary Objective: The primary objective is to determine the dose dependent effects of treatment with perindopril on MA-induced craving and on the reinforcing effects of MA indexed by MA self-administration. Secondary Objectives: To determine the dose dependent effects of treatment with perindopril on the positive and negative subjective effects of MA.
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