Rush Craig R, Santos Glenn-Milo, McMahan Vanessa M, Fraser Annie, Clark Jesse, Luna Marti Xochitl, Walker John E, Shoptaw Steve, Coffin Phillip O
Department 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.
Center on Substance Use and Health, San Francisco Department of Public Health, San Francisco CA, United States; Community Health Systems, School of Nursing, University of California San Francisco, San Francisco CA, United States; Center for HIV Identification, Prevention, and Treatment Services, University of California Los Angeles, Los Angeles, CA, United States.
Drug Alcohol Depend. 2025 Sep 1;274:112769. doi: 10.1016/j.drugalcdep.2025.112769. Epub 2025 Jun 24.
Previous trials showed mirtazapine reduces methamphetamine use. The present study determined the influence of mirtazapine treatment on the acute effects of methamphetamine.
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.
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.
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.
先前的试验表明米氮平可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效应的影响。
我们进行了一项安慰剂对照、交叉、双盲试验，以确定在米氮平（0、30mg/天）治疗5天后静脉注射甲基苯丙胺（0、30mg）的药效学效应。纳入了甲基苯丙胺使用障碍为中度至重度且甲基苯丙胺基线尿检呈阳性的健康成年人。米氮平和安慰剂的给药顺序随机分配，参与者在每种治疗条件下接受一次甲基苯丙胺输注。使用药物购买任务、主观效应问卷和心血管指标评估甲基苯丙胺的急性效应。
15名参与者（10名顺性别男性、4名顺性别女性、1名跨性别女性）参与了该试验。当参与者接受安慰剂治疗时，静脉注射甲基苯丙胺产生了典型的兴奋剂样效应（例如，假设的药物需求；“喜欢效应”评分、心率、血压升高）。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，甲基苯丙胺的主观和心血管效应相似。米氮平以及单独和联合输注甲基苯丙胺的耐受性良好。
米氮平降低了假设的药物需求，并且对生理盐水或甲基苯丙胺输注的耐受性良好。考虑到这些有利发现以及先前临床试验的结果，米氮平应继续作为甲基苯丙胺使用障碍的一种假定药物疗法进行测试。
