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Non-Addictive Pain Medication Shown Working in Animals

Spilled pills


30 August 2016. An experimental medication was shown in tests with monkeys to relieve pain for more than a day without the addictive properties or adverse physical effects of opioids. A report of the study conducted by researchers at Wake Forest University in Winston-Salem, North Carolina appears in yesterday’s issue of Proceedings of the National Academy of Sciences (paid subscription required).

The team led by physiology and pharmacology professor Mei-Chuan Ko is seeking an effective alternative to opioid pain relievers, which are responsible for an epidemic of abuse and overdoses due to their addictive nature. Centers for Disease Control and Prevention reports that since 1999, the amount of prescription opioids sold in the U.S. quadrupled, while the overall amount of pain reported by Americans has not changed. In 2014 as well, nearly 19,000 deaths involved prescription opioids, about 52 deaths per day, up from about 16,000 in 2013.

Opioids work by reducing the intensity of pain signals to the brain, particularly regions of the brain controlling emotion, which reduces effects of the pain stimulus. Ko and colleagues identified a synthetic compound code-named BU08028 that binds to nociceptin-orphanin FQ peptide, or NOP, and mu opioid peptide, or MOP, receptors in the brain. These are the same receptors targeted by buprenorphine, an opioid prescribed and given by physicians to control morphine or heroin addiction.

In its study, the Wake Forest team aimed to document the chemical and behavioral effects of BU08028 with animals most resembling humans. Earlier studies suggesting BU08028 targets the NOP and MOP receptors, but without the reinforcing effects that feed opioid addiction. In addition, the researchers sought evidence of the drug’s effects on respiratory and cardiovascular functions, two areas in which opioids can cause distress.

The authors tested BU08028 with 12 adult rhesus monkeys. The team found monkeys given BU08028 exhibited the same reactions indicating relief from pain stimuli as monkeys given opioids, including buprenorphine. The pain-relieving effects were also found to last at least 30 hours. Monkeys given BU08028 as well did not exhibit signs of respiratory or cardiovascular problems — even at many times the dose needed to relieve pain — as their counterparts given the synthetic opioid fentanyl.

In addition, the animals were trained to self-administer either BU08028, or known addictive opioids or cocaine. Tests with these drugs show monkeys taking BU08028 did not exhibit the reinforcing effects that feed addiction, like those taking opioids or cocaine. Likewise, monkeys receiving BU08028 did not show signs of excessive itching, or develop a physical dependence with repeated doses, as monkeys given opioids that exhibited withdrawal symptoms.

The authors note that further preclinical work with BU08028 is needed to determine long-term effects, including a build-up of tolerance to the drug over time. Nonetheless, in a Wake Forest statement Ko says, “this compound has almost zero abuse potential and provides safe and effective pain relief.” He calls the findings “a breakthrough for opioid medicinal chemistry that we hope in the future will translate into new and safer, non-addictive pain medications.”

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