19 August, 2025
breakthrough-analgesic-adriana-offers-hope-amid-opioid-crisis

Opioids such as morphine have long been a cornerstone of pain management in medical practice, owing to their potent analgesic properties. However, their use is fraught with risks, including respiratory depression and addiction. In response, Japan enforces stringent regulations to ensure these powerful medications are prescribed solely by authorized physicians.

In contrast, the United States has faced a different trajectory. The widespread prescription of the opioid OxyContin once led to a dramatic increase in the misuse of synthetic opioids like fentanyl. Consequently, the number of opioid overdose deaths soared past 80,000 in 2023, escalating into a national public health emergency now known as the “opioid crisis.”

ADRIANA: A New Hope in Pain Management

Amidst this backdrop, a promising alternative to opioids has emerged. Researchers at Kyoto University have discovered a novel analgesic, ADRIANA, which operates through a distinct mechanism. This breakthrough is part of an international collaborative effort, and clinical development is currently underway.

“If successfully commercialized, ADRIANA would offer a new pain management option that does not rely on opioids, contributing significantly to the reduction of opioid use in clinical settings,” says Masatoshi Hagiwara, a specially-appointed professor at Kyoto University.

Scientific Innovation Behind ADRIANA

The research team drew inspiration from substances that mimic noradrenaline, a chemical released during life-threatening situations that activates α2A-adrenoceptors to suppress pain. However, these substances often lead to cardiovascular instability. By focusing on noradrenaline levels and α2B-adrenoceptors, the team hypothesized that selectively blocking α2B-adrenoceptors could elevate noradrenaline levels, thus activating α2A-adrenoceptors and providing pain relief without cardiovascular risks.

To achieve this, the researchers utilized a novel technology known as the TGFα shedding assay to identify selective inhibitors of α2B-adrenoceptors and measure the activity of individual α2-adrenoceptor subtypes. This approach led to the discovery of the world’s first selective α2B-adrenoceptor antagonist.

Clinical Trials and Promising Results

Following successful administration of the compound to mice and comprehensive non-clinical safety assessments, clinical trials led by physicians at Kyoto University Hospital were conducted. Both the Phase I trial in healthy volunteers and the Phase II trial in patients experiencing postoperative pain after lung cancer surgery showed highly promising results.

Building on these positive outcomes, preparations are now in progress for a large-scale Phase II clinical trial in the United States, in partnership with BTB Therapeutics, Inc, a venture company originating from Kyoto University.

Implications for the Opioid Crisis

As Japan’s first non-opioid analgesic, ADRIANA holds the potential to not only alleviate severe pain for patients globally but also to play a crucial role in tackling the opioid crisis—a pressing social issue in the United States—and contribute to international public health efforts.

“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,” says Hagiwara.

Looking Forward: A New Chapter in Pain Management

The development of ADRIANA represents a significant milestone in the quest for safer pain management solutions. As the opioid crisis continues to challenge healthcare systems, the introduction of a non-opioid alternative like ADRIANA could mark a pivotal shift in how pain is treated worldwide.

Experts are optimistic that ADRIANA’s success could inspire further research into non-opioid pain relief options, ultimately reducing the dependency on opioids and improving patient outcomes. As clinical trials progress, the global medical community eagerly anticipates the potential impact of this groundbreaking analgesic.