The United States is battling a crisis with an increased number of drug over-dose death due to the addition of opioids, such as fentanyl and carfentanil into drugs of abuse. A 0.001 milligrams (mg) dose of carfentanil is enough to incapacitate someone. Michael Feasel, Ph.D., ECBC Toxicology and Obscurants Branch, has been studying the metabolism of carfentanil as well as the isolation and structure of the metabolites formed after introduction to the body.
Feasel’s study stemmed from a 2012 Defense Science and Technology Laboratory (DSTL), United Kingdom, publication which referenced carfentanil and remifentanil being utilized to quell the Moscow theatre hostage crisis in 2002.
Carfentanil inhibits neurons by activating the opioid receptors in the body and shutting down the respiratory and central nervous systems. Naloxone, an anti-overdose drug, works by reversing the effects caused by a narcotic. A 2 mg dose of naloxone can revive an overdose victim, but it has been reported that multiple doses of naloxone may be required for a carfentanil overdose.
If one could be certain of the amount of naloxone needed to resuscitate a carfentanil victim, lives could be saved in both the <FZ,1,0,3>narcotic usage and the defense communities. Feasel has proposed studies at ECBC to research such effects of removing the drug from cell receptors using substances such as naloxone.
“Higher potency versions of naloxone are available, however the Food and Drug Administration has not seen a need to get them approved for human use, until now. These ultra-potent opioid exposures are not only a chemical defense issue, but they are also a public health issue,” Feasel reported.
Feasel, who recently received a Ph.D. in toxicology at the University of Maryland, Baltimore School of Medicine, approached principal investigator Marilyn A. Huestis, Ph.D., then-chief of chemistry and drug metabolism at the National Institute on Drug Abuse’s (NIDA) Intramural Research Program about a collaboration on identifying carfentanil metabolites. Huestis recognized the epidemic and need to research carfentanil, and agreed to collaborate with Feasel and Robert Kristovich, Ph.D., ECBC Molecular Toxicology branch chief.
Feasel worked in NIDA’s labs for weeks incubating hepatocytes, commonly referred to as human liver cells, in a two-dimensional (2D) platform. Twelve metabolites were identified in total and the hepatocyte incubations showed slower clearance, providing some insight into the duration of carfentanil’s effects on the human body. Recent biological studies have shown cells forming on their own adhere to each other forming spheroids. Feasel conducted a follow-on study incubating carfentanil with three dimensional (3D) liver spheroids. In this instance the spheroids closely resembled a human liver organ versus the 2D platform which was similar to an individual cell. “By using a 3D subculture we are enabling the access to realistic data or in vivo metabolism,” observed Feasel.
Conclusions on this study have not yet been made as Feasel and his team are in the process of analyzing the data.
As carfentanil continues to make headlines the research being done at ECBC is vital as more information is brought to light about the substance.
“My goal with this study was to not only to understand this opioid, but to also bring the process and techniques of generating metabolite libraries to ECBC” remarked Feasel. “ECBC could apply the technique to unknown compounds which may be of interest to the CB defense community.”
By Edgewood Chemical Biological Center