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Updated: Sep 17, 2025
A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Mirtazapine reduces hypothetical methamphetamine demand in humans
Craig R Rush1, Glenn-Milo Santos2, Vanessa M McMahan3
1Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, United States; Center for HIV Identification, Prevention, and Treatment Services, University of California Los Angeles, Los Angeles, CA, United States.
Background:
Previous trials showed mirtazapine reduces methamphetamine use. The present study determined the influence of mirtazapine treatment on the acute effects of methamphetamine.
Methods:
We conducted a placebo-controlled, crossover, double-blind trial to determine the pharmacodynamic effects of intravenous methamphetamine (0, 30mg) after 5 days of mirtazapine (0, 30mg/day) treatment. Healthy adults with moderate to severe methamphetamine use disorder who had a positive baseline urine test for methamphetamine were enrolled. The order of mirtazapine and placebo was randomly assigned, and participants received a methamphetamine infusion during each treatment condition. Acute effects of methamphetamine were assessed using a drug purchasing task, a subjective effect questionnaire, and cardiovascular indices.
Results:
Fifteen (15) participants (10 cisgender males, 4 cisgender females, 1 transgender female) enrolled in the trial. Intravenous methamphetamine produced prototypical stimulant-like effects (e.g., hypothetical drug demand; increased ratings of Like Effect, heart rate, blood pressure) when participants were treated with placebo. Mirtazapine significantly decreased methamphetamine demand. The subjective and cardiovascular effects of methamphetamine were similar during mirtazapine and placebo treatment. Mirtazapine and infusions of methamphetamine, alone and combined, were well tolerated.
Conclusions:
Mirtazapine reduced hypothetical drug demand and was well tolerated with saline or methamphetamine infusions. Considering these favorable findings, along with those from previous clinical trials, mirtazapine should continue to be tested as a putative pharmacotherapy for methamphetamine use disorder.
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