Just Enough: What Amounts to Success for a Synthetic Opioid Antidote - DVIDS

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The first wave of deaths in the opioid epidemic began in 1999. By 2018, more than 450,000 Americans had died from opioid intoxication or overdoses,^{1, 2} and synthetic opioids had established themselves as an emerging threat to warfighters and first responders. An antidote for an opioid overdose is naloxone, but the amount that reverses an overdose of a natural opioid, such as morphine, is not effective against synthetic opioids such as carfentanil, a fentanyl-based sedative used on elephants and other large mammals.

Even an accidental exposure to microgram levels of carfentanil can lead to intoxication and the need for medical countermeasures that quickly reverse the adverse effects. But how much naloxone is an efficacious antidote? To answer this question, the Defense Threat Reduction Agency’s Chemical and Biological Technologies Department (DTRA CB) is supporting research performed by the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD).

USAMRICD scientists conducted naloxone safety and efficacy studies using a combination of physiological and behavioral assessments in two animal models (small animal and a nonhuman primate). The physiological assessment evaluates respiratory rate, heart rate, blood pressure, etc., for the efficacy and safety of the naloxone doses given to the animals to counter their exposures to carfentanil. The behavioral assessment makes use of reward-based tasks to identify when the animal returns to ‘normal’ behavior after exposure to carfentanil and administration of naloxone. The research seeks to identify the safe and efficacious dose of naloxone, the frequency in which that dose must be administered, and the point in time when the animal is able to quickly and correctly perform a reward-based task. Reward-based testing in a nonhuman primate has relevance for human-based tasks as the testing measures changes in speed and accuracy in performing a trained task.

Based on study data, scientists have identified the therapeutic dose (for official use only) of naloxone that safely and effectively reverses the effects of carfentanil intoxication. In 2019, results from this research were transitioned to the Joint Program Executive Office Medical Countermeasure Systems through a signed Data Transition Agreement. The research finding has enabled the Department of Defense’s Rapid Opioid Countermeasure System (ROCS) Program of Record to engage a pharmaceutical company to develop an autoinjector for administering the therapeutic dose of naloxone.

Through a separately funded effort, DTRA CB is also developing a higher concentration of naloxone that will be available in a larger, multidose vial. When taking care of warfighters and first responders exposed to carfentanil or an equally potent synthetic opioid, the availability of the vial of concentrated naloxone will enable the medic or clinician to prepare efficacious doses as needed and reduce the frequency of reaching for another vial of naloxone.
With the therapeutic dose of naloxone identified, research at USAMRICD continues, through DTRA CB’s support, to learn how often the dose must be administered to effectively reverse a fentanyl-based intoxication. In 2022, a stronger dose of naloxone will become available to warfighters and first responders who will be on the frontlines to defend themselves and others against attacks of carfentanil and other fentanyl-based synthetic opioids. The stronger drug may also help prevent deaths due to intoxication from synthetic opioids.

POC: Kensey Amaya, This email address is being protected from spambots. You need JavaScript enabled to view it.

^1. Centers for Disease Control and Prevention (CDC). Opioid data analysis and resources. CDC website. https://www.cdc.gov/drugoverdose/data/analysis.html. [Page last reviewed on March 19, 2020.] Accessed May 26, 2020.

^2. Healthline. 2018. Opioid intoxication. Healthline website. https://www.healthline.com/health/ opioid-intoxication. [Page last reviewed on September 7, 2018.] Accessed May 26, 2020.