The primary objective is to determine the dose dependent effects of treatment with perindopril on methamphetamine (MA)-induced craving and on the reinforcing effects of MA indexed by MA self-administration. We will also determine the effects of treatment with candesartan on MA-induced craving and on the reinforcing effects of MA indexed by MA self-administration.
Our preliminary data indicate that the ACE inhibitor perindopril can attenuate MA-induced drug craving, suggesting that perindopril should be evaluated as a treatment for MA dependence. Candesartan works similarly to perindopril but should lack the U-shaped dose response. Like perindopril, candesartan is used for hypertension. Whereas perindopril reduces the synthesis of angiotensin II, candesartan blocks angiotensin II receptors.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
80
8 mg taken orally from days 0 through 7.
Placebo treatment daily.
16 mg taken orally from days 0 through 7.
Michael E. DeBakey VA Medical Center
Houston, Texas, United States
The dose-dependent effects of an ace inhibitor or an angiotensin receptor blocker on MA- and cue-induced craving and on the reinforcing effects of MA indexed by MA self-administration.
Participants demonstrating MA-induced craving will then be randomized to active study medication (perindopril or candesartan) or matched placebo (day 0). Over days 4 to 7 a variety of procedures will be completed to assess effects of MA and cue-induced craving. On day 7, reinforcing effects will be assessed will be assessed using self-administration procedures.
Time frame: 7 days
The effects of an ace inhibitor or an angiotensin receptor blocker on subjective measures.
On days 3 and 5, participants will receive sample doses of 15mg or 30mg MA paired with a dose of placebo saline separated by 180 min, with the order of administration randomized. Subjective effects of MA will be assessed using visual analogue scales (VAS).
Time frame: 7 days
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