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Countering opioid side effects

A genetic screen in worms reveals a receptor target to battle opioid addiction The toll from opioid overdose in the United States now exceeds 45,000 deaths per year. Shockingly, more Americans die from opioid overdose than from motor vehicle collisions (1), and opioid overdose has become the number one cause of accidental death. Worldwide, two-thirds of drug-related deaths were a result of opioids, as reported by the United Nations 2019 drug report. As well as searching for opioid replacements, scientists are developing therapeutics to block the detrimental side effects of opioids, particularly addiction and fatal opioid-induced respiratory depression (OIRD) (2). Addiction and OIRD are a direct result of opioid activation of receptors that regulate neural circuits that control reward and breathing—circuits distinct from those that regulate pain (3). On page 1267 of this issue, Wang et al. (4) identify the orphan G protein–coupled receptor (GPCR) GPR139 as a regulator of opioid receptors and provide evidence that this receptor could be a useful therapeutic target to reduce opioid side effects.