In what has been called a potential “holy grail” of opioid research, scientists at Wake Forest Baptist Medical Center have created what they are calling a non-addictive opioid compound, a result which could have widespread repercussions for pain treatment and the ongoing opiate addiction crisis.
Reported in the journal Proceedings of the National Academy of Sciences, the study profiles the synthetic opioid BU08028 which was tested on 12 non-human primates and found to not only be an effective pain killer but also to be free of adverse side effects such as decreased respiratory function and, importantly, addiction.
“Based on our research, this compound has almost zero abuse potential and provides safe and effective pain relief,” says Mei-Chuan Ko, professor of physiology and pharmacology at Wake Forest Baptist and lead author of the study. “This is a breakthrough for opioid medicinal chemistry that we hope in the future will translate into new and safer, non-addictive pain medications.”
Ever since heroin was first synthesized in the late 1800s -and initially proclaimed to be free from the hazards of abuse- research efforts have been ongoing in the quest to create an opioid analgesic which does not promote addictive behaviour. And while advances in pharmacology over the past few decades have produced dozens of synthetic opioids currently in use for pain management, from effective pain killers like oxycodone and the extremely potent fentanyl to opioid antagonists such as naloxone that block the body’s receptor sites from taking in other opioids, the prospect of the addiction-free opioid has remained out of reach.
But scientists see real potential in BU08028, which binds to two opioid receptors in the body named MOP and NOP like the known compound buprenorphine but is said to have improved activity over buprenorphine at NOP receptors. Researchers studied the behavioral, physiological and pharmacological effects of BU08028 on non-human primates and found the drug to be highly potent and long-lasting in its analgesic effect while not inhibiting respiratory or cardiovascular functioning or causing acute physical dependence.
“To our knowledge, the present study provides the first functional evidence in nonhuman primates that BU08028 with mixed MOP/NOP agonist activities is an effective and safe analgesic without apparent abuse liability or other opioid-associated side effects,” say the study’s authors.
In a commentary on the new study, Dr. Jun-Xu Li of the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo has written of the opioid’s “double-edged sword.” “Despite their effectiveness, opioids produce many clinically significant side effects.” says Li. “For decades, research pursued the ‘Holy Grail’ of opioid analgesic research: the development of opioids that retain the analgesic efficacy with reduced side effects. [The new study] reports a systematic evaluation of a novel opioid, BU08028, may lead us one step closer to this ultimate goal.”
The use and abuse of opioids for pain treatment has reached crisis levels in Canada and the United States. Last year in Canada alone, 21.7 million opioid prescriptions were dispensed, a 20 per cent increase over the previous half-decade.