These scientists have been working to find a safe, non-addictive pain killer to help fight the current opioid crisis in this country – and they may have done just that.

Known as AT-121, the new chemical compound has dual therapeutic action that suppressed the addictive effects of opioids and produced morphine-like analgesic effects in non-human primates.

“In our study, we found AT-121 to be safe and non-addictive, as well as an effective pain medication,” said Mei-Chuan Ko, professor of physiology and pharmacology at the School of Medicine.

“In addition, this compound also was effective at blocking abuse potential of prescription opioids, much like buprenorphine does for heroin, so we hope it could be used to treat pain and opioid abuse.”

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The research, which was conducted by scientists at Wake Forest School of Medicine with the support of the National Institute on Drug Abuse, is published in the journal Science Translational Medicine.

The main objective of this study was to design and test a chemical compound that would work on 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, work only on the mu opioid receptor, which also produces unwanted side effects – 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,” Ko said.

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In the study, the researchers observed that 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.

The bifunctional profile of 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 itch, respiratory depression, tolerance and dependence.

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“Our data shows that targeting the nociceptin opioid receptor not only dialed down the addictive and other side-effects, it provided effective pain relief,” Ko said. “The fact that this data was in nonhuman primates, a closely related species to humans, was also significant because it showed that compounds, such as AT-121, have the translational potential to be a viable opioid alternative or replacement for prescription opioids.”

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 clinical trials in people, Ko said.

(Source: Wake Forest Baptist Medical Center)

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  1. Wow! That certainly is good news! Now maybe we won’t need to legalize marijuana to kill pain! One less excuse for stoners to get high all the time, so maybe they will become productive individuals. We can only hope–

    • Not sure where to begin.
      Firstly, I don’t think a passive aggressive attack on a group of recreational cannabis users is appropriate for a site based dedicated to positivity. Perhaps that wasn’t your intent but it certainly came across that way.
      More importantly, I’m afraid all of your implicit assumptions are incorrect.
      Firstly, about 20% of all young people use cannabis. The number who turn into “stoners” is comparable with the number of people who consume alcohol and turn into drunks. I.e. very few.
      Secondly, the there are two reasons for legalization of cannabis which have nothing to do with therapeutic use: (i) it redirects black market profits from armed gangs into the public coffers and (ii) it removes the public hypocrisy of having one standard for highly addictive and dangerous drugs like alcohol and tobacco an another for (relatively) safer cannabis.
      Finally, the kind of acute pain relief provided by opioids is one very minor medical use for cannabis. It has been used successfully in treating chronic pain, it reduces anxiety in terminal patients, it reduces seizures and mitigates some of the worst effects of MS and other neuro-degenerative disorders, it significantly reduces the horrible involuntary muscle contraction in muscular dystrophy sufferers and it has recently been demonstrated to alleviate intractable depression. There is also anecdotal evidence that it is effective in reducing pain and inflammation for rheumatoid arthritis sufferers.
      It is an act of the utmost insanity to have allowed such a polyvalent drug with a lengthy history as a traditional medicine and sacred plant and such a low abuse profile to have languished in the shadowy world of organized crime in supposedly developed nations for so long.
      It is certainly the height of spitefulness to want to outlaw something that can bring so much comfort to so many because a tiny percentage of people might abuse it. Even if they did, surely that is their own concern.

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