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A UCLA Health study reveals that a drug used to treat insomnia could potentially prevent opioid addiction in mice, even when used at opioid doses that provide strong pain relief.
The research indicates that suvorexant, typically prescribed for insomnia, might also inhibit opioid addiction by blocking hypocretin receptors in the brain. This dual action allows it to maintain effective pain relief while reducing addiction-related brain changes, suggesting promise for safer pain management strategies.
Led by UCLA Health, the study, published today in Nature Mental Health, found that suvorexant’s ability to block hypocretin receptors prevents opioid addiction in mice. At human-equivalent low doses effective in preventing addiction, suvorexant did not induce sleep but maintained behavioral alertness.
Hypocretin, also known as orexin, plays a crucial role in mood regulation. Its release peaks during pleasurable activities and decreases during painful or sad experiences. Loss of hypocretin neurons is linked to narcolepsy, a condition hypothesized to involve autoimmune factors. Individuals with narcolepsy, along with narcoleptic mice, exhibit reduced susceptibility to opioid addiction.
In both humans addicted to heroin and morphine-addicted mice, increased numbers of hypocretin-producing neurons have been observed. Morphine use enhances the connectivity of hypocretin neurons with brain regions associated with pleasure.
The study in mice demonstrated that combining opioids with suvorexant prevented opioid-induced changes in hypocretin neurons. It also halted the increase in connections between hypocretin neurons and reward-related brain areas, significantly reduced opioid-triggered brain inflammation, and prevented addictive behaviors such as conditioned place preference for morphine.
Moreover, administering suvorexant alongside morphine substantially alleviated morphine withdrawal symptoms in the study.
Dr. Jerome Siegel, senior author of the study from UCLA Health’s Jane & Terry Semel Institute for Neuroscience and Human Behavior, the UCLA Brain Research Institute, and the U.S. Department of Veterans Affairs, emphasized the urgent need for new opioid addiction treatments. He highlighted the annual toll of over 80,000 opioid overdose deaths in the U.S., surpassing fatalities from car accidents and gun violence.
While non-opioid pain relievers suffice for mild pain, conditions like severe burns, cancer, and chronic joint inflammation often necessitate opioid therapy. Dr. Siegel stressed the necessity for further research to determine if suvorexant’s addiction-suppressing effects observed in mice translate to humans, potentially offering a safer and more effective approach to pain management without the risk of addiction and overdose.
The study involved 170 mice receiving morphine over 14-day periods, alongside postmortem brain analyses of five individuals with opioid use disorder and five control subjects. Clinical trials are essential to confirm whether suvorexant can replicate its addiction-suppressing effects in humans using opioids for pain relief, Dr. Siegel concluded.
