The Quest for New Pain Medications: Developments in Non-Opioid Painkillers Offer Hope for Pain Relief without Addiction

The opioid crisis has been a significant public health concern, leading to changes in formulary guidelines regarding opioid use. In response, scientists worldwide are intensifying their efforts to develop non-opioid painkillers. This article explores these efforts and the promising alternatives on the horizon.

Emerging Non-Opioid Painkillers

In response to the danger of opioid use and concurrent with The Centers for Disease Control and Prevention (CDC) guidelines, promising developments in non-opioid painkillers are offering hope for patients and clinicians alike. Several new non-opioid medications have emerged on the market, offering novel mechanisms of action and reduced risks of addiction.


Recently, scientists have developed a new non-opioid painkiller called BnOCPA (benzyloxy-cyclopentyladenosine), which has shown promising results in test model systems.[1] BnOCPA is a potent and selective analgesic that does not induce sedation or affect motor function.[2] Many drugs act via proteins on the cell surfaces that activate adapter molecules called G proteins. The activation of G proteins can lead to many cellular effects. BnOCPA is unique in that it only activates one type of G protein, leading to very selective effects and thus reducing potential side effects.

Dr. Mark Wall, from the School of Life Sciences at the University of Warwick, who led the research said, “The selectivity and potency of BnOCPA make it truly unique and we hope that with further research it will be possible to generate potent painkillers to help patients cope with chronic pain.”[3]

Furthermore, BnOCPA is not only effective in relieving pain, but also non-addictive, offering a significant advantage over traditional opioid painkillers.[4]

  1. VX-548

Another experimental pain drug that may offer an alternative to opioids has shown promise in two small clinical trials for acute pain. Vertex Pharmaceutical’s compound, called VX-548, outperformed a placebo in phase 2 trials for two types of postsurgical pain.

As discussed in our recent article, Could There Be a Medication That Combats Acute Pain Without Serious Systemic Side Effects Like Addiction?,[5] these trials show positive results and more importantly strengthen the proof-of-principle for continuing down this path for an effective analgesic without serious addicting side effects. These promising results pave the way for larger trials that could lead to regulatory approval.

  1. Naltrexone

Yet another promising trial has shown potential for non-opioid treatment for patients, specifically, patients with orofacial and chronic pain. Unlike traditional pain management that focuses on treating the injury or trauma site, this study used low doses of naltrexone (0.1-4.5 mg), which work by acting on a unique cellular pathway in the nervous system. In this way, chronic pain relief was delivered without opioids and therefore, without the risk of addiction.

In the study, conducted by the University of Michigan School of Dentistry, first author Elizabeth Hatfield said, “We found a reduction in pain intensity and improvement in quality of life, and a reduction in opioid use for patients with chronic pain.”[6]

Furthermore, “low-dose naltrexone begins to address the cause of pain and not just mask it, which allows us to better target diseases causing chronic pain, as well as potentially consider pain control outside of opioid use,” Hatfield reported.[7]

Other Emerging Medications

In a recent Newsweek article, Pain Relief Without Opioids: Alternative Treatments That Work, David H. Freedman reported that “sixteen new non-opioid pain-relief drugs are currently in phase III trials, which means some of them could come to market in the next few years, and some may be available now to patients willing to be part of a trial.”[8]

“In addition, eight new pain-relief drugs based on cannabis-derived compounds are currently in phase III trials. Another highly experimental drug, AT-121, is not as far along the testing pipeline, but early studies show that it may ease pain and help with opioid addiction recovery.”[9]

Future Clinical Implications and Patient Benefits

The development of these new non-opioid medications carries significant implications for the future of clinical practice. Healthcare providers will have additional tools at their disposal to tailor pain management strategies to individual patient needs. The reduced risk of addiction and adverse effects associated with these emerging medications will contribute to a safer and more patient-centered approach to pain relief.


While the advent of non-opioid medications represents a major advancement, challenges persist. Further research is needed to expand our understanding of the long-term effects, optimal dosages, and potential interactions with other medications. Additionally, efforts to raise awareness among healthcare professionals and patients about these alternatives will be crucial to ensuring their widespread adoption.

In response to the opioid crisis, The CDC released guidelines for prescribing opioids, reflecting the latest scientific understanding and clinical best practices.[10] A summary of these most recent guidelines follows:

The 2022 Clinical Practice Guideline for Prescribing Opioids for Pain addresses four key areas:

  1. Determining whether to initiate opioids for pain.
  2. Selecting opioids and determining opioid dosages.
  3. Deciding the duration of the initial opioid prescription and conducting follow-up.
  4. Assessing risk and addressing potential harms of opioid use.

The CDC’s guideline also emphasizes the importance of individualized patient care, safe and effective pain management options, and improved communication between clinicians and patients. Reducing risks associated with opioid pain therapy, including opioid use disorder, overdose, and death, are also discussed.[11]

For more in-depth information on opioid management, the CDC published a webinar in the Clinician Outreach and Communication Activity (COCA) Call Series. The webinar discusses CDC recommendations, implementation principles, and approaches to maximize benefits and minimize risks when starting, continuing, or discontinuing opioids for pain. To access the CDC webinar, click here:


The ongoing development of non-opioid painkillers and the updated CDC guidelines represent significant strides in pain management. These advancements underscore the importance of patient-centered care and the need for safe, effective, and individualized treatment options.

If you have any questions about the new CDC guidelines for opioid management, please contact us.