Mirtazapine reduces hypothetical methamphetamine demand in humans

IF 3.6 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2025-06-24 DOI:10.1016/j.drugalcdep.2025.112769

Craig R. Rush , Glenn-Milo Santos , Vanessa M. McMahan , Annie Fraser , Jesse Clark , Xochitl Luna Marti , John E. Walker , Steve Shoptaw , Phillip O. Coffin

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Abstract

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, 30 mg) after 5 days of mirtazapine (0, 30 mg/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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米氮平减少了人类对甲基苯丙胺的假想需求

背景：先前的试验表明米氮平可以减少甲基苯丙胺的使用。本研究确定了米氮平治疗对甲基苯丙胺急性反应的影响。方法采用安慰剂对照、交叉、双盲试验，观察米氮平（0,30 mg/d）治疗5天后静脉注射甲基苯丙胺（0,30 mg/d）的药效学效果。有中度至重度甲基苯丙胺使用障碍的健康成人，基线甲基苯丙胺尿检呈阳性。米氮平和安慰剂的顺序是随机分配的，参与者在每个治疗条件下接受甲基苯丙胺输注。通过药物购买任务、主观效果问卷和心血管指数来评估甲基苯丙胺的急性效应。结果15名参与者（10名顺性别男性，4名顺性别女性，1名变性女性）入组试验。静脉注射甲基苯丙胺产生了典型的兴奋剂样作用(例如，假设的药物需求；当参与者接受安慰剂治疗时，相似效应（Like Effect）、心率、血压的评分都有所增加。米氮平显著降低了甲基苯丙胺的需求。在米氮平和安慰剂治疗期间，甲基苯丙胺的主观效应和心血管效应相似。米氮平和输注甲基苯丙胺，单独或联合，耐受性良好。结论咪氮平降低了假设药物需求，并与生理盐水或甲基苯丙胺输注耐受良好。考虑到这些有利的发现，以及先前临床试验的结果，米氮平应该继续作为甲基苯丙胺使用障碍的推定药物治疗进行测试。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug and alcohol dependence 医学-精神病学

CiteScore

7.40

自引率

7.10%

发文量

409

审稿时长

41 days

期刊介绍： Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.