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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Addictive Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1441598

Evaluating the Antagonist Effect of Naltrexone Implant via Opioid Challenge Tests with Escalating Doses of Hydromorphone Injection in Former Heroin-Dependent Patients

Provisionally accepted
Wei Hao Wei Hao 1*Wei Qu Wei Qu 2Xuyi Wang Xuyi Wang 1Chongyang Dong Chongyang Dong 3Tao Zhang Tao Zhang 2Shugui Yin Shugui Yin 2Zhijun Sun Zhijun Sun 2Shiqiang Wang Shiqiang Wang 2Anni Guo Anni Guo 2
  • 1 Institute of Mental Health of the Second Xiangya Hospital of Central South University, National Medical Center for Mental Disorders, Changsha, Anhui Province, China
  • 2 Shenzhen Sciencare Pharmaceutical Co., Ltd., Shenzhen, China
  • 3 Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China

The final, formatted version of the article will be published soon.

    Opioid dependence is a serious, life-threatening condition with severe social impacts. Naltrexone (NTX) can weaken the effect of opioids and effectively reduce opioid selfadministration, discrimination, and opioid-induced subjective effects, and the oral dosage form has been approved for the treatment of opioid dependence. However, the effectiveness of oral naltrexone as an opioid antagonist has been limited due to poor patient adherence. A long-acting formulation in the form of naltrexone implant (NTX-IMP) with a five-month duration of action may address this issue and improve outcomes.This study (trial registration number: CTR20181954) aimed to evaluate the effect, safety, and pharmacokinetics of NTX-IMP in agonist effects via hydromorphone challenge test, and to determine optimal dosages for future research. Thirty-one former opioid-dependent individuals were randomized to the 0.9g or the 1.5g NTX-IMP group.All subjects exhibited significant antagonistic effects during hydromorphone challenge test. Calculation of slope between VAS score or pupil diameter and hydromorphone dose suggested a stronger antagonistic effect in the 1.5 g group. Pharmacokinetic data suggested that effective plasma naltrexone concentration (≥1ng/ml) was detected from the third day for over 148 days, with higher concentration and longer duration in the 1.5 g group. All subjects tolerated NTX-IMP well. The findings indicate that the NXT-IMP effectively blocks the agonistic effects of hydromorphone in a dose-dependent manner.

    Keywords: Naltrexone, Opioid blockage, Opioid challenge, Hydromorphone, Longacting naltrexone implant (NTX-IMP)

    Received: 31 May 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Hao, Qu, Wang, Dong, Zhang, Yin, Sun, Wang and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Wei Hao, Institute of Mental Health of the Second Xiangya Hospital of Central South University, National Medical Center for Mental Disorders, Changsha, Anhui Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.