Safer opioids may be on the horizon, but mitigating addiction is a long shot

Abstract

Opioids are well-known to be lethally addictive, spurring a nationwide crisis. Less well-known are the drugs’ other complications: dangerous breathing difficulties, nausea, gastrointestinal distress, and paradoxically, a hypersensitization that worsens feelings of pain. Inevitably, frequent users grow tolerant of the drugs’ pain-relieving effects, leading them to use increasingly higher doses of opioids, which can spiral into lethal respiratory depression. Multiple research efforts are trying to find opioid alternatives that target the opioid receptor without the usual slew of dangerous side effects. Image courtesy of Shutterstock/Tomas Nevesely. Clearly, there are good reasons to seek alternatives. But a challenge looms: although some newer drugs for chronic pain do target alternate cellular pathways, nothing else is quite as effective as opioids at treating acute trauma. “As much as we wish there were something that worked better than or at least as well as the endorphin pathway mediated by the μ-opioid receptor, we haven’t found it yet,” says Jonathan Violin, senior vice-president of scientific affairs at Pennsylvania-based biopharma startup Trevena and an adjunct professor at Duke University Medical Center. These hurdles are well-known. In June, the NIH announced a new initiative, dubbed Helping to End Addiction Long-term (HEAL), that aims to address the issues of opioid addiction in a many-pronged effort (1). One arm of the initiative aims to find safer drugs and new drug targets, developing new therapies for opioid-induced respiratory depression, and improving existing medications. In fact, efforts to find these safer alternatives to opioids are already well underway. Academic researchers and startups seeded in academic laboratories, as well as large pharmaceutical companies, are testing a range of molecules that target opioid receptors yet lack the slew of side effects. Some of these alternatives work by binding the opioid receptor in unique ways, whereas others act only in peripheral tissues that need …