Researchers from Rutgers University believe they have discovered the molecular mechanism behind drug and alcohol addiction and that this mechanism may be treatable with already available insomnia medications.
Current research from the Rutgers Brain Health Institute and elsewhere shows that the orexin system in the brain, which controls sleep/wake states, reward systems, and mood, encourages drug-seeking behavior, according to a review in Biological Psychiatry. According to the research, many addictive substances boost orexin synthesis in both animal and human brains, and inhibiting this pathway can cure addiction in animals. Even one of the three orexin-blocking sleep aids licensed for the treatment of insomnia has been shown in another research to lessen opiate cravings in human participants.
According to Gary Aston-Jones, co-author of the analysis and head of the Brain Health Institute, “there is still much to learn about how orexin drives drug seeking, but we know more than enough to support exploring orexin antagonists in clinical trials as addiction therapies.”
- Chronic Anxiety: Symptoms, Causes and Treatments
- Antidepressants in Pregnancy: Different Countries, Different Views
The review, which is based on more than a decade’s worth of writings by Rutgers and other academics, reveals that orexin increases drug appetite and, consequently, incentive to buy drugs.
In a typical state, the brain’s many orexin-producing cells switch motivation-boosting and motivation-lowering orexin production on and off. These cells switch on when individuals, for instance, have a pressing deadline and must complete work, and they turn off at night so that people may sleep.
However, these cells enhance orexin production rather than decreasing it when people get addicted to opioids, cocaine, alcohol, and other drugs. They never turn off and generate large amounts of orexin, which drives one behavior—getting more hits.
Researchers have been able to thoroughly analyze each stage in the process through controlled experiments using mice, rats, zebrafish, and other species. The orexin system in humans has increased, just as it has in animal addicts, according to postmortem examination of heroin users’ brain tissue. This overactivity may persist indefinitely once it is initiated; in fact, the study team found elevated orexin levels in cocaine-dependent rats that had maintained sobriety for more than a quarter of their normal lifespan.
Three anti-orexin insomnia drugs have been licensed by the US Food and Drug Administration as a result of earlier research on the sleep-blocking effects of orexin (Belsomra, Quviviq and Davigo). Researchers have explored these drugs as addiction therapies, primarily on animals, as the function of orexin in addiction has become more apparent. Low dosages of one of these drugs have been shown in Rutgers research to decrease drug-seeking behavior in rats without sedating them or compromising cognitive function. Additionally, a recent research from Johns Hopkins University demonstrated that this drug helps lessen cravings in opioid detoxification patients.
Despite the fact that there is no assurance that orexin agonists can successfully treat addiction, Morgan James, coauthor of the paper and a professor of psychiatry at Rutgers Robert Wood Johnson Medical School, expressed optimism. “Additionally, there is a great demand for efficient therapies. The number of overdose deaths has soared over 100,000 annually, and the effectiveness of available treatments is low.”
More information: Morgan H. James et al, Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction, Biological Psychiatry (2022). DOI: 10.1016/j.biopsych.2022.06.027
