Clinical Trial: Dose Response of Mirtazapine to Methamphetamine Induced Interest, Mood Elevation and Reward
Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional
Official Title: Dose Response of Mirtazapine to Methamphetamine Induced Interest, Mood Elevation and Reward
Brief Summary:
The primary purpose of this study is to determine if Mirtazapine will produce a decrease in interest in the drug, a decrease in mood elevation, and/or a decrease in reward when given before methamphetamine compared to placebo.
Participants will be screened with a psychiatric interview, medical history and physical, laboratory tests, drug of abuse screen and, if female, a urine pregnancy test. They will be provided written informed consent. They will be studied in a within-subjects examination of the subjective mood responses of mirtazapine and methamphetamine. Interactions between methamphetamine and mirtazapine will be assessed by pharmacokinetic studies. Each participant will be introduced to rating scales and cognitive tasks described below. Participants will remain in the research unit for 5 hours on each day that they receive study medication or placebo. They will spend five days in total on the research unit, one day separated by at least one day; then in two day blocks separated by at least one day from another two day block. A venous catheter will be placed for blood draws. Blood pressures and heart rates will be recorded and assessed. Participants will be randomized and double blinded to receive either placebo or mirtazapine orally two hours prior to the administration of randomized and double blinded methamphetamine or placebo in order to have the peak effects of the drugs overlap. VAS-mood, ARCI, GRS, POMS and POMS-E, neurocognitive tasks Trails A and B and Symbol digits modalities test will be administered prior to the mirtazapine or placebo dose, and repeated after the administration of methamphetamine or placebo. After the administration of methamphetamine or placebo, vital signs will be assessed every 15 minutes and the measures will be repeated until 120 minutes have passed from the initial dose of methamphetamine or placebo. Blood will be drawn at one, th
Detailed Summary:
Methamphetamine dependence is a major health problem in the US. Methamphetamine's reinforcing effects associated with its abuse liability depend upon activation of the cortico-mesolimbic dopamine (CMDA) system. Medications that antagonize CMDA function might have therapeutic potential Mirtazapine appears to affect this pathway. Mirtazapine works through serotinergic (5-HT) mechanisms 5HT 2 and 3, alpha 2 and H1 antagonist and has been noted to decrease excitatory responses in methamphetamine challenged animals. Mirtazapine increases dopamine release in the prefrontal cortex by 5HT receptor activation. Additionally, in a randomized, placebo controlled trial; individuals taking mirtazapine for amphetamine detoxification were found to have significant improvements in hyper arousal and anxiety subset score when discontinuing the stimulant. Methamphetamine has been given safely to healthy human volunteers in other studies.
We propose to conduct the first preliminary human laboratory study to determine if mirtazapine 15 mg diminishes methamphetamine (20 mg) induced positive subjective interest, mood elevation and reinforcing value. This dose of methamphetamine has been used by other investigators in healthy volunteers.
This preliminary trial is the first in a sequence of studies to characterize the dose dependent effects of mirtazapine as a treatment agent for methamphetamine dependence. If this study is successful, it would afford us a scientific platform and rationale for progressing with testing efficacy for mirtazapine among methamphetamine dependent individuals both in the human laboratory and in clinical trials. The primary objective of this study is to evaluate systematically the neurobehavioral basis and dose-response effects of mirtazapine acutely on methamphetamine-induced interest, mood elevation and reward. This stud
Sponsor: University of Virginia
Current Primary Outcome: extent to which mirtazapine reduces methamphetamine induced mood elevation, reward, and interest [ Time Frame: At each study visit ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: University of Virginia
Dates:
Date Received: January 10, 2008
Date Started: September 2007
Date Completion: July 2010
Last Updated: April 26, 2011
Last Verified: April 2011
