# Mirtazapine for methamphetamine use disorder: drug-drug interaction study

> **NIH NIH U01** · PUBLIC HEALTH FOUNDATION ENTERPRISES · 2020 · $2,205,587

## Abstract

Project Summary/Abstract
Methamphetamine use is a major driver of drug-related morbidity and mortality, with intimate involvement in
the national opioid crisis as well. Methamphetamine is more prevalent than many other drugs, including
opioids, with 37 million users of methamphetamine and amphetamine worldwide and 1.4 million past-year
users in the U.S. alone in 2016. The annual economic cost of methamphetamine use is estimated to be $23.4
billion in the United States. There are no FDA-approved pharmacotherapies for methamphetamine use
disorder, a major gap in the field of addition medicine. Promising agents such as bupropion, extended-release
naltrexone, aripiprazole, and selected amphetamine-based stimulants, have all shown mixed or negative
results in phase 2 clinical trials. In contrast, in two separate phase 2 clinical trials mirtazapine has
demonstrated a significant effect in increasing periods of abstinence from methamphetamine and decreasing
related HIV risk behaviors among adults with methamphetamine use disorder who were born male and have
sex with men. While testing this product in the general population, with larger samples sizes, and more
intensive adherence interventions is demanded, the first step required by the FDA is now a drug-drug
interaction study to evaluate pharmacokinetics of methamphetamine in the presence of mirtazapine, to
evaluate for adverse events such as QT prolongation and serotonin syndrome, and to ensure the safety of
these combinations in patients with co-morbid opioid use disorder who may be using illicit opioids or
maintained on agonist therapy. We propose to conduct this Phase 1 human laboratory trial, also exploring
mechanisms for the effect of mirtazapine with a battery of psychological testing, with 36 subjects (Group 1 with
no opioid use, Group 2 with illicit opioid use, Group 3 with opioid use disorder maintained on methadone) in a
within-subject crossover study. After screening, participants will be admitted to a 16-day inpatient stay,
randomly assigned to mirtazapine or placebo, followed to steady state, and given placebo and a
methamphetamine infusion with associated batteries of psychological testing; they will then be followed for 5
days for washout and initiated in the opposite treatment arm. Results will contribute toward further evaluation
of mirtazapine for treatment of methamphetamine use disorder.

## Key facts

- **NIH application ID:** 9983371
- **Project number:** 1U01DA051080-01
- **Recipient organization:** PUBLIC HEALTH FOUNDATION ENTERPRISES
- **Principal Investigator:** PHILLIP O COFFIN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,205,587
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983371

## Citation

> US National Institutes of Health, RePORTER application 9983371, Mirtazapine for methamphetamine use disorder: drug-drug interaction study (1U01DA051080-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983371. Licensed CC0.

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