DOX as a Potential Treatment for Methamphetamine Dependence

Purpose: To determine the effects of treatment with doxazosin, compared to treatment with placebo, on methamphetamine-induced craving and subjective effects in methamphetamine-dependent human volunteers. Secondary aims are to clarify the genetics of substance abuse, potentially leading to improved methods to diagnosis those at risk and to help develop better therapeutic interventions and to develop a new saliva-based test for the detection and measurement of drugs of abuse. Design/Procedure: Twenty non-treatment-seeking methamphetamine-dependent volunteers will complete procedures during treatment with placebo and study medication, in random order, using a within-subjects, double-blind, placebo-controlled design. There will be a two week period between each phase. The dose of doxazosin needed to alter the effects of methamphetamine is unknown and preclinical animal studies have not been conducted. Because of this, initially the investigators will study the effects of a low dose of doxazosin (4mg daily) compared to placebo daily. Methamphetamine (0, 10, and 30mg, smoked) will be administered during treatment with 4mg doxazosin/placebo. Methamphetamine will be administered in ascending dose (10mg followed by 20mg) with the 0mg dose randomly interspersed to maintain the blind. Cardiovascular measures and subjective effects ratings will be assessed following methamphetamine administration. Participants will be monitored for stability on days 11 and 12 and discharged from the hospital on day 13. If 4mg doxazosin treatment is well tolerated but is not associated with alterations in the effects of methamphetamine, a second group of subjects will be studied using the same sample size. Treatment will begin at 1mg and increased by 1mg increments every three days until 8mg is reached. Placebo will be dosed identically. All study procedures will be identical as described above.