Mirtazapine reduces hypothetical methamphetamine demand in humans.

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.