Countermeasures for Preventing and Treating Opioid Overdose

Abstract

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large‐scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans‐agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5‐HT)1A receptor agonists; (5) fentanyl‐binding cyclodextrin scaffolds; (6) detoxifying biomimetic “nanosponge” decoy receptors; and (7) antibody‐based strategies. These approaches could also be applied to treat opioid use disorder.

Gas Chromatography-Mass Spectrometry Analysis of Synthetic Opioids Belonging to the Fentanyl Class: A Review

“…[19][20][21] To this end, several approaches are currently under development to counteract the effects of this class of lethal compounds, these medical countermeasures seek to provide an additional preventive layer of protection to the affected individual and removing the heavy reliability on the limited efficacy of naloxone, naltrexone and other forms of treatment currently used in emergency situations. [22][23][24][25][26][27] It has been briefly noted above that one of the most notorious facets of synthetic opioids, specifically those belonging to the fentanyl family, is their use as incapacitating agents. A modern example of this use is highlighted by the Moscow Dubrovka Theater siege in 2002.…”

The Pharmacological War Against and With Opioids

“…The only currently available medication for treating opioid overdose is the competitive, reversible opioid receptor antagonist, naloxone, which was approved by the US Food and Drug Administration (FDA) half a century ago 3 . Although naloxone is classed as an Essential Medicine by the World Health Organization (WHO), 4 there is growing concern about its lack of effectiveness in treating OIRD caused by novel synthetic opioids, such as fentanyl, which combine a higher potency with faster onset and longer duration of action 5 …”

“…As explained by Paul Janssen 35 years ago, 11 synthesis of carfentanil is relatively straightforward, and 1 kilogram could provide 20 million fatal doses 12 . In the current CPT issue, France et al 5 . provide a detailed summary of an expert meeting that was convened in 2019 by the Chemical Countermeasures Research Program (CCRP) to explore emerging alternative pharmacological approaches for treating opioid overdose in the event of weaponization of synthetic opioids, including: Intranasal nalmefene Methocinnamox Covalent naloxone nanoparticles Serotonin 5HT 1A receptor agonists Fentanyl‐binding cyclodextrin scaffolds Biomimetic “nanosponge” decoy receptors Vaccines and monoclonal antibodies …”

Early Detection of Exposure to Toxic Chemicals Using Continuously Recorded Multi-Sensor Physiology

“…In the current study, and as a first step towards detecting intoxication following chemical exposure in humans using wearable sensors, we assessed detection and identification of acute exposure to two distinct potent chemicals in guinea pigs using continuously recorded electrocardiogram (ECG), electroencephalogram (EEG) and respiration in combination with machine learning techniques. The chemicals used were an opioid, fentanyl, and a nerve agent, VX, both potent chemicals that could be weaponized and used as warfare agents by state actors or terrorist organizations [ 15 , 16 ]. Fentanyl and VX were used as model compounds to study exposure scenarios involving inhalational exposure to a potent opioid, or skin exposure to a nerve agent, respectively.…”