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Latest Research Offers Alternative to Addictive Opioids

Posted by Rebecca James on Sep 26, 2018 3:00:00 PM

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The misuse of and addiction to opioids—including prescription pain relievers, heroin, and synthetic opioids such as fentanyl—is a growing national crisis affecting public health and creating an enormous burden on the healthcare system.  The Centers for Disease Control and Prevention estimates that the total economic impact of prescription opioid misuse in the United States is $78.5 billion a year, including healthcare, lost productivity, addiction treatment, and criminal justice involvement.

According to the National Institute of Drug Abuse:

  • Approximately 21 to 29 percent of patients prescribed opioids for chronic pain misuse them
  • Between 8 and 12 percent develop an opioid use disorder
  • An estimated 4 to 6 percent who misuse prescription opioids transition to heroin
  • About 80 percent of people who use heroin first misused prescription opioids
  • Opioid overdoses increased 30 percent from July 2016 through September 2017 in 52 areas in 45 state
  • The Midwestern region saw opioid overdoses increase 70 percent from July 2016 through September 2017
  • Opioid overdoses in large cities increase by 54 percent in 16 states

Finding an alternative to highly addictive opioids has become an active area of research, with the potential to save lives-and money.  Scientists at Wake Forest School of Medicine have been working to find a safe, non-addictive pain killer to help fight the current opioid crisis, opioid-crisis-infographic-1and they have demonstrated promising results in animal models.

The researchers ave been studying the efficacy of a compound known as AT-121, which exhibits dual therapeutic action that suppressed the addictive effects of opioids and produced morphine-like analgesic effects in non-human primates.  The findings were published in the Aug. 29 issue of Science Translational Medicine.

Mei-Chuan Ko, Ph.D., professor of physiology and pharmacology at the School of Medicine, said that AT-121 was both safe and non-addictive, as well as an effective pain medication.  In addition to having potent analgesic properties, the compound also showed promise at treating opioid abuse.

The primary focus of the study was to target both the mu opioid receptor, the main component in the most effective prescription pain killers, and the nociceptin receptor, which opposes or blocks the abuse and dependence-related side effects of mu-targeted opioids. Current opioid pain drugs, such as fentanyl and oxycodone, affect the mu opioid receptor, producing unwanted side effects such as respiratory depression, abuse potential, increased sensitivity to pain and physical dependence.

"We developed AT-121 that combines both activities in an appropriate balance in one single molecule, which we think is a better pharmaceutical strategy than to have two drugs to be used in combination," -Mei-Chuan Ko, Ph.D. 

In the study, AT-121 showed the same level of pain relief as an opioid, but at a 100-times lower dose than morphine. At that dose, it also blunted the addictive effects of oxycodone, a commonly abused prescription drug.  AT-121 not only gave effective pain relief without abuse potential, it also lacked other opioid side-effects that patients typically struggle with, such as respiratory depression, tolerance and dependence.  The demonstrated efficacy combined with lack of dangerous side effects makes AT-121 a promising candidate for further development.  Next steps include conducting additional preclinical studies to collect more safety data, and then if all goes well, applying to the Food and Drug Administration for approval to begin human clinical trials.

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