A drug commonly used to treat insomnia may hold the key to preventing opioid addiction while still providing effective pain relief, according to new research led by UCLA Health. The study, published in Nature Mental Health, reveals that suvorexant, a medication that blocks brain receptors for the neurotransmitter hypocretin, successfully prevented addictive effects of morphine in mice.
Suvorexant, typically prescribed in high doses to induce sleep in humans, proved effective at much lower doses in mice. These lower doses prevented opioid addiction without causing drowsiness or affecting behavioral alertness.
The Hypocretin Connection to Opioid Addiction
Hypocretin, also known as orexin, plays a crucial role in mood regulation. Its release in humans peaks during pleasurable activities and drops during pain or sadness. Interestingly, people with narcolepsy, a condition caused by the loss of hypocretin neurons, show a significantly lower susceptibility to opiate addiction.
Previous research has shown that both humans addicted to heroin and mice addicted to morphine develop higher numbers of hypocretin-producing neurons. Morphine also causes these neurons to increase their connections to pleasure-related brain regions.
Suvorexant’s Promising Results in Mice
The UCLA-led study found that administering opioids with suvorexant in mice produced several positive outcomes:
1. Prevention of opioid-induced changes in hypocretin neurons
2. Reduction in connections between hypocretin neurons and brain reward regions
3. Significant decrease in opioid-induced brain inflammation
4. Prevention of addictive behaviors, such as anticipatory running for daily morphine doses
5. Substantial reduction in morphine withdrawal symptoms
“The annual US rate of opioid overdose deaths now exceeds 80,000, greater than the annual rates of automobile or gun deaths,” said the study’s senior author, Dr. Jerome Siegel of UCLA Health’s Jane & Terry Semel Institute for Neuroscience and Human Behavior, the UCLA Brain Research Institute and U.S. Department of Veterans Affairs. “Non-opioid analgesics are able to relieve relatively minor pain. But severe burns, cancer, joint inflammation, sickle cell disease, bone damage and many other painful conditions often cannot be effectively treated with non-opioid analgesics.
“Further studies are needed to determine if the addiction suppressive results seen in mice given suvorexant with morphine are also seen in humans, potentially allowing safer, more effective treatment of pain without the risk of addiction and opioid overdose death,” Siegel continued.
The study involved 170 mice administered morphine over 14-day periods, as well as postmortem brain examinations of 5 humans with opiate use disorder and 5 control human brains. While the results are promising, clinical trials are necessary to determine if suvorexant will be as effective in suppressing addiction in humans using opioids for pain relief as it is in mice.
This research offers hope for a potential breakthrough in the ongoing opioid crisis, potentially providing a safer approach to pain management without the risk of addiction.
