BRIEF RESEARCH REPORT article
Front. Neurosci.
Sec. Neuropharmacology
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1654787
Proof of Concept for High-Dose Cannabidiol Pretreatment to Antagonize Opioid Induced Persistent Apnea in Mice
Provisionally accepted
- University of California, Los Angeles, Los Angeles, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Opioid related fatalities remain a public health crisis in the US. Currently, the only way to restore breathing following an opioid induced persistent apnea is with the administration of the opioid antagonist naloxone, but it also reverses analgesia, euphoria, and induces precipitated withdrawal in opioid dependent individuals. Methods: Using whole-body plethysmography, we assessed changes in breathing frequency in awake behaving mice resulting from a single fentanyl dose (50 mg/kg i.p.) that followed i.p. pretreatment with saline, vehicle, naloxone (100 mg/kg), cannabidiol (CBD) (250 mg/kg), or CBD+naloxone. Then we assessed the delay to opioid-induced persistent apnea (OIPA) and the median lethal dose (LD50) of fentanyl during a continuous i.c.v. infusion of fentanyl (100 ng/min), in urethane anesthetized mice, following pretreatment with saline, vehicle, naloxone (100 mg/kg), CBD (250 mg/kg), or CBD+naloxone i.p. Results: Here we show acute pretreatment with CBD is as effective as naloxone at preventing opioid-induced respiratory depression from fentanyl in awake mice, and increasing LD50 of fentanyl in urethane anesthetized mice. When pre-administered together, CBD+naloxone, increased LD50 of fentanyl even more than CBD or naloxone alone in urethane anesthetized mice. Conclusions: CBD may be an effective preventative therapy for OIPA by increasing the time before apnea onset and potentially enhancing the efficacy of naloxone as an additional strategy to save lives.
Keywords: cbd, Opioids, breathing, oipA, OIRD
Received: 26 Jun 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 Wiese, Bondarenko and Feldman. 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: Jack L. Feldman, feldman@g.ucla.edu
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.