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Synthetic Opioid Addiction May be More Prevalent due to Brain Reactions

May 16, 2018
New research explains how fentanyl and other unnatural opioids activate receptors.

A PPM Brief

A research team led by Miriam Stoeber at the University of California San Francisco examined how certain drugs may differ from peptides in their actions on target neurons. While opioid receptors modulate behavior when activated by native peptide ligands, they also distort behaviors to produce pathology when activated by non-peptide drugs, according to the authors’ summary, published online in Neuron

The team developed a genetically encoded biosensor that directly detects ligand-induced activation of opioid receptors (ORs) to probe the cellular basis of neuromodulation. With this new tool, researchers were able to “uncover a real-time map of the spatiotemporal organization of OR activation in living neurons.” The biosensor demonstrated how drugs differ in the subcellular location at which they activate, essentially identifying distinct patterns in terms of how brain neurons react differently to opioid substances created inside the body versus reactions caused by opioid medications (eg, morphine) and by synthetic opioids (eg, fentanyl).

The findings may change the way synthetic drugs are understood in terms of addiction. Natural and synthetic opioids activate receptors in the Golgi apparatus, where endogenous opioids are unable to produce any activation at all, summarized UCSF in a news piece.  “It really surprised us that there was a separate location of activation for drugs in the Golgi apparatus that could not be accessed by endogenous opioids,” said Dr. Stoeber. “Drugs, which we generally thought of as mimics of endogenous opioids, actually produce different effects by activating receptors in a place that natural molecules cannot access.”

Added Mark von Zastrow, MD, PhD, a professor of psychiatry at UCSF and senior author on the new paper: “There has been no evidence so far that opioid drugs do anything other than what natural opioids do, so it’s been hard to reconcile the experiences that drug users describe – that opioid drugs are more intensely pleasurable than any naturally rewarding experience that they’ve ever had…. The possibility that these opioid drugs cause effects that natural opioids cannot is very intriguing because it seems to parallel this extremely rewarding effect that users describe.”

The research was supported in part by funding from the National Institute of Drug Abuse, the Canadian Institutes of Health Research, and the Swiss National Science Foundation.

Last updated on: May 18, 2018
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