Summary: A preclinical study found that suvorexant (Belsomra), an insomnia drug, could be a potential treatment for opioid use disorder (OUD) in mice.
If the results are replicated in humans, the drug could offer a promising treatment for millions of people with OUD and reduce drug use and prevent relapse.
Key Facts:
- Preclinical studies suggest that the insomnia drug suvorexant may be an effective treatment for opioid use disorder, reducing prescription opioid intake and protecting against relapse in mice modeling opioid use disorder.
- The study’s findings may offer a promising approach for the millions of people who have OUD and have not been helped by current treatments, such as methadone, buprenorphine, and naltrexone.
- Suvorexant is designed to inhibit the activity of both orexin-1 and orexin-2 brain-cell receptors, which are also involved in the drug addiction process.
Source: Scripps Research Institute
The insomnia drug suvorexant (Belsomra) may be an effective treatment for opioid use disorder, according to a preclinical study from Scripps Research.
In the study, published on April 27, 2023, in Frontiers in Pharmacology, Scripps Research scientists found that suvorexant reduced prescription opioid use and helped protect against relapse in mice modeling opioid use disorder (OUD). If the results translate to humans in clinical trials, the insomnia drug could offer a promising option for the millions of people with OUD.
“Our results suggest that repurposing suvorexant may be a promising strategy for reducing drug intake and preventing relapse in cases of prescription opioid abuse,” said senior author of the study. student Rémi Martin-Fardon, Ph.D., associate professor in the Department of Molecular Medicine at Scripps Research.
The study’s first author is Jessica Illenberger, Ph.D., a postdoctoral research associate in the Martin-Fardon lab.
In the US alone, OUD is estimated to affect more than two million people, approximately 80,000 of whom die each year from opioid-related overdoses in an ongoing epidemic that has contributed to a dramatic decline on the average life expectancy of Americans. Available treatments for OUD include methadone, buprenorphine and naltrexone, but most patients relapse, making the need for better treatment urgent.
How suvorexant has a beneficial effect on OUD is not entirely clear, but it is designed to inhibit the activity of both orexin-1 and orexin-2 brain-cell receptors. These receptors and their binding partners, known as orexin proteins, have been studied primarily for their roles in maintaining wakefulness, appetite, and general arousal and alertness.
Over the past two decades, however, evidence has accumulated that orexin signaling also helps maintain the drug addiction process, indicating that it may be a promising target for treatments.
Suvorexant, approved by the US Food & Drug Administration (FDA) for the treatment of insomnia in 2014, is the first drug that inhibits the activity of both orexin receptors. In a study published earlier this year, Martin-Fardon and colleagues found that suvorexant reduced alcohol consumption and blocked relapse in a rat model of alcohol use disorder. .
In the new study, Martin-Fardon and her team examined the potential of suvorexant in reducing use and preventing relapse in OUD—specifically involving the powerful and frequently abused prescription painkiller oxycodone.
Suvorexant is cleared from the bloodstream more quickly in rats than in humans, but researchers found that when oxycodone-dependent rats were given a maximum dose (20 mg/kg) of suvorexant half an hour later before their oxycodone binge sessions, they were independent. administered significantly less opioid during the first hour of each eight-hour session.
Next, the researchers used a relapse model in which an auditory cue reminded the long-absent rats of their previous oxycodone binges. This normally triggers the reinstatement of strong oxycodone-seeking behavior, but the maximum dose of suvorexant completely blocked this reinstatement in male rats, and significantly reduced its severity in women.
Martin-Fardon says the weaker effect on women isn’t surprising, because—consistent with findings in many other addiction studies—they’re clearly more affected by opioid dependence: During their binges, they take more than twice the amount of oxycodone that men did, and their relapses were also stronger.
“If you’re going to treat people, you have to consider whether the same dose of suvorexant will work equally well for men and women,” Martin-Fardon added.
Overall, he said, the findings show that suvorexant has an effect against both oxycodone use during addiction and relapse after abstinence, and thus is worth studying in those clinical trial in oxycodone dependent patients.
He is now planning a follow-on preclinical study of whether suvorexant can restore the normal sleep-wake cycle and thereby prevent relapse in animal models of oxycodone dependence.
Elsewhere, researchers have begun small clinical trials of suvorexant as an add-on therapy in patients with substance use disorders.
About this neuropharmacology and OUD research news
Author: Press Office
Source: Scripps Research Institute
Contact: Press Office – Scripps Research Institute
Image: Image credited to Neuroscience News
Original Research: Open access.
“Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats” by Jessica M. Illenberger et al. Frontiers in Pharmacology
Abstract
Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats
Background: The Department of Health and Human Services reported that the misuse of prescription pain relievers (eg, oxycodone) was initiated by 4,400 Americans per day in 2019. Amid the opioid crisis, effective strategies to prevent and treat prescription opioid use disorder (OUD) is compulsive. In preclinical models, the orexin system is recruited by drugs of abuse, and blockade of orexin receptors (OX receptors) inhibits drug-seeking behavior. The current study sought to determine whether repurposing suvorexant (SUV), a dual OX receptor antagonist marketed for the treatment of insomnia, can treat two features of prescription OUD: excessive consumption and relapse.
Method: Male and female Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, iv, 8 h/day) in the presence of a contextual/discriminative stimulus (S).D) and the ability of SUV (0–20 mg/kg, po) to reduce oxycodone self-administration was tested. After self-administration testing, rats underwent extinction training, after which we tested the ability of SUV (0 and 20 mg/kg, po) to prevent relapse to oxycodone seeking elicited by S.D.
Results: Rats were able to self-administer oxycodone and use was associated with signs of physical opioid withdrawal. Additionally, women self-administer approximately twice as much oxycodone as men. Although SUV had no overall effect on oxycodone self-administration, investigation of the 8-h time-course revealed that 20 mg/kg SUV decreased oxycodone self-administration during the first hour in both males and females. Oxycodone SD induced strong reinstatement of oxycodone-seeking behavior that was more robust in females. Suvorexant blocked the finding of oxycodone in men and reduced it in women.
Conclusions: These results support targeting OX receptors for treatment for prescription OUD and repurposing SUV as pharmacotherapy for OUD.
