Opioids without the risk of addiction?

Scientists are working to develop medicines that have the pain-relieving effects of opioids without the high risk of misuse and addiction. Since misuse is linked to the euphoric effects of the drug, investigators led by scientists at NIDA’s intramural labs are studying methadone, a drug used to manage opioid addiction that does not have euphoric effects as strong as many other opioids.

PET scan images in rats showing a much weaker ability of methadone than morphine to influence metabolic activity in the area of the nucleus accumbens. Courtesy: Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, NIDA IRP

Animal studies show that mu opioid receptors in the brain play a key role in the reinforcing effects of opioid drugs, whereas the neuropeptide galanin counteracts the effects of mu opioid receptors. In a recently published study, investigators found a significant difference in the mechanisms of action between methadone and morphine that is determined by the activation of opioid receptor complexes (heteromers) composed of both mu-opioid receptors and one of the galanin receptor subtypes; differences that are key to their subsequent effects on the brain’s dopamine system.

The investigators found that the opioid-galanin receptor heteromers determine the different effects of methadone as compared to morphine and fentanyl, showing methadone with a weaker ability to activate the dopaminergic system linked to the euphoric effects of opioids. These results should advance the search for opioids less likely to attach to opioid-galanin receptor heteromers, exemplified by methadone. This finding also enables the search for compounds that activate galanin receptors, which would be expected to reduce the abuse liability of opioids.

The research was done by scientists at NIDA’s intramural labs in Baltimore, the University of Maryland, Harvard Medical School, and the University of Barcelona.

For a copy of the article, published in Journal of Clinical Investigation, go to Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.

For more information, go to Opioids.

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