This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Original Research

The Mixed Opioid Receptor Antagonist Naltrexone Mitigates Stimulant-Induced Euphoria: A Double-Blind, Placebo-Controlled Trial of Naltrexone

Thomas J. Spencer, MD; Pradeep Bhide, PhD; Jinmin Zhu, PhD; Stephen V. Faraone, PhD; Maura Fitzgerald, MPH; Amy M. Yule, MD; Mai Uchida, MD; Andrea E. Spencer, MD; Anna M. Hall, BA; Ariana J. Koster, BS; Leah Feinberg, BS; Sarah Kassabian, BS; Barbara Storch, BS; and Joseph Biederman, MD

Published: March 13, 2018

Article Abstract

Objective: Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD).

Methods: We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH.

Results: Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ2 = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ2 = 0.22, P = .64) of SODAS-MPH treatment.

Conclusions: Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential.

Trial Registration: ClinicalTrials.gov identifier: NCT01673594

Volume: 79

Quick Links: ADHD , Neurodevelopmental

Continue Reading…

Subscribe to read the entire article

$40.00

Buy this Article as a PDF

References

Sign-up to stay
up-to-date today!

SUBSCRIBE

Already registered? Sign In

Original Research

Effect of Zuranolone on Concurrent Anxiety and Insomnia Symptoms in Women With Postpartum Depression

Zuranolone was associated with improvements in depressive and anxiety symptoms and was beneficial for insomnia and patient-perceived...

Read More...