Forensic toxicologists have had their hands (and workloads) full in recent years as the opioid epidemic wages on and novel psychoactive substances (NPS) continue to evolve in an attempt to evade detection.
Recent research by scientists at the University of Southern California (USC) and the National University of Singapore (NUS) seeks to address at least some of today’s challenges in forensic toxicology.
A safer opioid
In a study published last week, scientists from USC, Washington University in St. Louis and Stanford University demonstrated that by chemically linking fentanyl to the sodium pockets that exist within nerve cell receptors, they could block the drug’s harmful side effects and still reduce pain.
“In its current form, fentanyl is like a weapon of mass destruction,” said Vsevolod Katritch, a computational scientist at the Bridge Institute at USC Michelson Center for Convergent Bioscience and a corresponding author of the study. “Our new collaborative work suggests that we could redesign the drug in such a way that we convert this frequent overdose killer to a much more benign but still effective analgesic.”
Drugs of all kinds are designed to target certain receptors on nerve cells known as GPCRs, or G-protein coupled receptors, which act as signal transmitters. These receptors are like switches that mediate a drug’s intended effect on the brain and body, but also the unintended side effects.
Katritch and his collaborators said that although further study is needed to prove that their less harmful version of fentanyl will work in humans, the results have opened a new door for scientists to potentially improve the safety of painkillers.
“We are desperately looking for ways to maintain the analgesic effects of opioids, while avoiding dangerous side effects such as addiction and respiratory distress that too often lead to death," said corresponding author Susruta Majumdar of Washington University in St. Louis. “Our research is still in its early stages, but we’re excited about its potential for leading to safer pain-relieving drugs.”
Synthetic cannabinoids
Meanwhile, researchers at NUS focused their most recent study on an emerging subclass of synthetic cannabinoids called OXIZID—a synthetic cannabinoid first identified in Singapore in 2021.
Synthetic cannabinoid consumption is typically identified via the detection of biomarkers in urine. These biomarkers are often metabolites of the original synthetic cannabinoid consumed, as cannabinoids are known for their rapid and extensive metabolism in the human body.
But, researchers say little is known about the metabolite profile of OXIZID, beyond the fact that it has a unique molecular scaffold. Thus, the team’s newest research investigated the key metabolic properties and identified urinary biomarkers of four OXIZID analogues—BZO-HEXOXIZID, BZO-POXIZID, 5F-BZO-POXIZID and BZO-CHMOXIZID. The specific analogues were selected since they were identified both in Singapore and internationally.
According to the study published in Clinical Chemistry, the researchers started by identifying 12 to 16 major metabolites of each of the four OXIZID analogues. They then narrowed down the selection to three metabolites that could serve as reference urinary biomarkers to detect OXIZID consumption. The metabolites were identified due to them being unique markers found in high abundance in urine samples following OXIZID consumption.
“The identification of the three new metabolites will facilitate work by drug enforcement agencies worldwide in monitoring OXIZID abuse,” said the researchers.
The NUS team also determined critical enzymes responsible for major metabolic pathways involved in the rapid metabolism of OXIZIDs.
“These findings can facilitate the greater understanding of the toxicological implications of OXIZID consumption. This could help predict metabolite profiles of new synthetic cannabinoids with similar core structure as well as drug interactions between OXIZIDs and other illicit drugs or medications,” explain the researchers.
Singapore’s Health Sciences Authority has already applied the research findings in routine analysis to monitor OXIZID consumption in the nation. The NUS team said they will continue their research to tackle future emerging synthetic cannabinoids.