A new study led by UC San Francisco scientists shows that brain cells, or neurons, react differently to opioid substances created inside the body – the endorphins responsible for the “natural high” that can be produced by exercise, for example – than they do to morphine and heroin, or to purely synthetic opioid drugs, such as fentanyl. The researchers say their findings may help explain why the use of synthetic opioids can lead to addiction.
Since both synthetic opioids and the natural, “endogenous” opioids produced in the brain bind to and activate opioid receptors on the surface of nerve cells, scientists have long assumed that both types of molecules target the same cellular systems. But the new research reveals that these molecules also activate opioid receptors inside cells, and that the locations of these activated intracellular receptors differ between natural and synthetic opioids.
In the new study, published in the May 10 issue of Neuron, the researchers report that this difference could help explain why the effects of synthetic opioid drugs are more rewarding than those produced by endogenous opioids.
“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,” said Mark von Zastrow, MD, PhD, a professor of psychiatry at UCSF and senior author on the new paper. “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.