Could this new Japanese drug end the dangers of opioids for pain relief?

A Kyoto University team has developed ADRIANA, a first-of-its-kind non-opioid painkiller that could rival morphine and fentanyl, without addiction or deadly side effects

Severe pain has long been treated with opioids like morphine and fentanyl, but their use comes with devastating risks such as addiction, overdose, and even death. In a bid to find a safer solution, researchers at Kyoto University have developed a new oral drug named ADRIANA that provides opioid-level pain relief without the dangers of dependence or respiratory failure.

 

According to a study published in the Proceedings of the National Academy of Sciences (PNAS) titled “Discovery and development of an oral analgesic targeting the α2B adrenoceptor,” early clinical trials suggest this discovery could reshape the future of pain management and help address the global opioid crisis.

 

What makes ADRIANA different from morphine or fentanyl?

In the United States, aggressive prescribing of opioids such as OxyContin fuelled an addiction crisis. By 2023, opioid overdoses were responsible for over 80,000 deaths, most linked to fentanyl, which is 50 times stronger than heroin.

 

ADRIANA does not act on the brain’s opioid receptors. Instead, it targets α2B-adrenoceptors, which influence how the body releases noradrenaline—a natural chemical that suppresses pain in emergency situations.

 

By selectively blocking α2B-adrenoceptors, ADRIANA enhances noradrenaline’s ability to activate α2A-adrenoceptors. This provides strong pain relief without disrupting cardiovascular function or causing respiratory failure.

 

“Our compound is not an opioid, so there are no adverse effects and no addiction, making it very safe,” said Masatoshi Hagiwara, the study’s corresponding author and a professor at Kyoto University, in a statement published on the university website.

How effective is this new painkiller?

According to the study, the results so far are extremely promising:

• Animal studies in mice and monkeys showed ADRIANA relieved pain as effectively as morphine, but caused no signs of addiction, anxiety, or depression.
• Phase I trials in healthy volunteers confirmed the drug was safe.
• Phase II trials in lung cancer surgery patients at Kyoto University Hospital found ADRIANA provided strong postoperative pain relief without sedation or dependence.
• A larger Phase II trial in the United States is now being prepared in collaboration with BTB Therapeutics, a Kyoto University spinoff. If successful, the drug could reach patients in just a few years.

Could this drug help fight the opioid crisis?

The researchers believe ADRIANA could give doctors a safer tool to manage severe pain in cancer care, surgery recovery, and chronic pain patients—reducing reliance on dangerous opioids.

 

“We aim to evaluate the analgesic effects of ADRIANA across various types of pain and ultimately make this treatment accessible to a broader population of patients suffering from chronic pain,” said Hagiwara.

 

If large-scale US clinical trials confirm its effectiveness, ADRIANA could become available within two to three years, researchers estimate. 

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