(2R,6R)-Hydroxynorketamine for Acute Pain

This trial tests a new drug, (2R,6R)-hydroxynorketamine (HNK), to determine its effectiveness in reducing acute pain without the addictive risks of opioids. HNK, related to ketamine, may relieve pain with fewer side effects. The study examines the drug's impact on pain and emotions by analyzing brain activity. Ideal candidates are healthy adults without chronic pain or psychiatric conditions who can attend appointments at the NIH Clinical Center in Bethesda, Maryland. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Yes, participants must stop taking any prescription or nonprescription drugs, including over-the-counter medicines, herbal remedies, or dietary supplements, at least 14 days before receiving the study drug.

Earlier studies have shown promising safety results for (2R,6R)-hydroxynorketamine (HNK) in humans. Research indicates that HNK, derived from ketamine, might relieve pain similarly to ketamine but with fewer side effects. Importantly, HNK does not carry the same addiction risk as ketamine.

Although researchers have not extensively studied HNK's safety for pain management, existing data is encouraging. For instance, studies in mice have shown that HNK can reduce pain without the negative effects often seen with other pain medications.

Most treatments for acute pain rely on opioids or non-steroidal anti-inflammatory drugs (NSAIDs), which can have significant side effects and risks. But (2R,6R)-hydroxynorketamine, or (2R,6R)-HNK, works differently by targeting the NMDA receptors in the brain, potentially leading to pain relief without the same addictive properties or side effects associated with opioids. Researchers are excited about (2R,6R)-HNK because it may offer fast-acting pain relief and a safer alternative to traditional pain medications, reducing the risk of dependency and improving patient outcomes.

Research has shown that (2R,6R)-hydroxynorketamine (HNK) might reduce pain similarly to ketamine but with fewer side effects. Animal studies have found that HNK effectively relieves sudden inflammatory pain and post-surgical pain. However, other research suggests it might not work for all types of sudden pain. Some studies highlight its potential to reduce sensitivity to touch (mechanical allodynia) and improve nerve-related pain, with results similar to current treatments. In this trial, participants will receive a single intravenous infusion of HNK, a placebo, or no treatment to assess its effectiveness in treating sudden pain in humans. Overall, while HNK appears promising, its effectiveness remains under study.¹³⁴⁵⁶