An Opioid That Doesn’t Cause Addiction or Overdose? Is This Really Possible?

Michael Nguyen PharmD, CPh
Director of Clinical Services

Like all drugs, opioids can cause side effects. However, beyond the commonly reported effects such as nausea, constipation, dizziness and sedation, there is one side effect that presents the biggest obstacle to the usefulness of opioids: euphoria. Euphoria is a feeling of pleasure, excitement, well-being and happiness that has the potential to cause some unsuspecting patients to misuse opioid medications.

As it currently stands, America is experiencing the worse opioid addiction epidemic problem in history. According to the Centers for Disease Control (CDC), 72,237 people died of drug overdoses in 2017. Sixty-six percent of drug overdoses (47,600) involved an opioid.1

While there are many ways in which the country is working to fix the opioid epidemic, some scientists are going back to the drawing board to look for drugs that can be as powerful and effective as existing opioids (e.g., morphine; oxycodone; hydrocodone) without the detrimental side effects of opioids.

According to a 2018 study published in the medical journal Science Translational Medicine, scientists at Wake Forest School of Medicine in North Carolina have discovered a potential drug named AT-121 that provides opioid level pain relief without causing addiction or overdose.2 AT-121 targets the same opioid receptors (i.e., mu opioid receptors) as other opioids, but also activates another group of receptors known as nociceptin/orphanin FQ peptide (NOP) receptors. Activation of mu opioid receptors located throughout the brain and spinal cord leads to pain relief, but also causes other reactions in the body such as euphoria and respiratory depression (i.e., the mechanisms leading to addiction and overdose). Activation of the NOP receptors counteracts such reactions. The researchers tested AT-121 on rhesus monkeys and found that it is 100 times more potent than morphine for pain relief but did not induce opioid side effects such as respiratory depression, abuse potential, opioid-induced hyperalgesia and physical dependence.

Given these preliminary positive findings, AT-121 will be nothing less than a miracle drug and a game changer for the pain management industry if it is eventually developed into a marketed drug. The next step for the development of this drug is human studies. If the effects of AT-121 are as positive in humans as in monkeys, AT-121 has the potential to turn the opioid industry upside down. Given the arduous and lengthy process of drug development (i.e., FDA approval), it will likely take many years to get AT-121 on the market and available to patients. In the meantime, opioids will remain the conventional choice for severe pain and continue to plague patients with a myriad of side effects up to and including death.

1National Institute on Drug Abuse. “Overdose Death Rates.” NIDA, 9 Aug. 2018, www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates.

2Ding H, Kiguchi N, Yasuda D, et al. A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates. Science Translational Medicine. 2018; 10(456). doi:10.1126/scitranslmed.aar3483

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