Updates in Opioid Alternatives

The opioid crisis is a public health emergency that has had a devastating impact on the US, taking the lives of a staggering 80,411 people in 2021 alone. This epidemic has been a tragedy for those who have lost their lives, and researchers and policymakers alike are searching for ways to put an end to this crisis. Various research labs are exploring alternative analgesics to opioids that offer hope for a brighter, safer future. Join us as we delve into the hopeful and necessary developments in this field.

Combating the Opioid Epidemic with Safer Alternatives

Ongoing research into pain management alternatives, non-opioid medications, and addiction treatment approaches are some of the main methods being used to address the opioid crisis. The FDA is included in this push towards safer alternatives, and they released a draft guidance in 2022 to encourage the development of non-addictive alternatives to opioids for managing acute pain. The aim is to reduce opioid exposure and prevent new addictions, and the guidance outlines recommendations for companies developing non-opioid analgesics, addressing aspects such as drug development programs, labeling claims regarding opioid use reduction, and the use of expedited FDA programs to support development. Although public health measures are equally paramount to the reduction of opioid deaths, the search continues for the optimal pain reliever: one that reduces pain but does not induce an addictive or dependent response.

Pioneers in Opioid Alternative Research

Most opioids on the market today—including morphine, oxycodone, and codeine—target the Mu opioid receptor, which is found on the surface of certain cells in the body, including neurons in the central nervous system. The Mu receptor plays a crucial role in mediating the effects of opioid drugs, and when activated by opioid drugs or endogenous opioids, the Mu opioid receptor initiates a cascade of intracellular events that result in various physiological and psychological responses. These responses include pain relief, sedation, euphoria, respiratory depression, and the potential for addiction. Understanding the Mu opioid receptor and its interactions with opioids is important for developing new medications to treat pain effectively while minimizing the risk of adverse effects and addiction. Researchers are actively studying the Mu opioid receptor and its signaling pathways to develop safer and more targeted treatments for pain management.

Academic institutions, including Shandong University, Yantai University, and Tulane University, are working on novel analgesics that target the Mu opioid receptor. Shandong and Yantai Universities are collaborating to create a Mu-receptor agonist that has a favorable toxicity profile for a novel analgesic. Tulane University’s James Zadina, PhD, in collaboration with the University of Arizona, is also developing an opioid alternative analgesic. Zadina’s breakthrough revolves around a novel opioid alternative pain medication derived from a cyclic peptide that specifically targets the Mu receptor, and this innovative analgesic demonstrates remarkable effectiveness against a wide spectrum of pain, including acute, neuropathic, inflammatory, postoperative, and visceral pain. In fact, its efficacy surpasses that of morphine in certain rodent models, presenting a promising solution for pain management. Unlike its counterparts, this alternative does not possess the same addictive potential, offering hope for individuals suffering from chronic pain, recent injuries, or those undergoing surgical procedures. By minimizing the risk of addiction, this groundbreaking development ensures that patients can receive effective pain relief without compromising their long-term well-being.

Other esteemed universities are actively engaged in exploring different innovative strategies such as utilizing other market drugs and discovering new compounds to address opioid use disorder and improve pain management. Geneva University Hospitals conducted a study where palliative care adults were given intranasal dexmedetomidine—a drug used for sedation—for pain relief, finding this drug to be a feasible alternative to opioids for long-term nursing care. The University of Arkansas is taking a different approach by looking at therapeutic compounds for opioid use disorder, and the University of Warwick is approaching pain medication by creating a compound that targets a specific G-protein receptor. Studying different pharmaceutical targets for pain relief opens the door for innovative solutions that will hopefully one day provide an end to this crisis.

As of October 2022, pharmaceutical companies have 16 new pain medications in Phase III trials with indications ranging from post-operative pain to chronic pain. One such example from this long list of new pain medications is Vertex Pharmaceutical’s compound which was created from research on sodium channels located on pain-sensing neurons. The implications of each of these advancements extend far beyond a single solution: they hold the potential to revolutionize the way people approach pain treatment, benefiting countless individuals worldwide.

Looking Ahead: The Promise of Opioid Alternatives

The opioid epidemic has had far-reaching consequences, devastating lives and straining vital public resources. However, through visionary research conducted at many academic, pharmaceutical, and governmental institutions, a brighter path has emerged. Opioid alternative drugs hold immense potential in reshaping the landscape of pain management, offering effective analgesia while minimizing the detrimental side effects and addiction risks associated with traditional opioids. With collaborative efforts from various high-level universities and a big push from government institutions such as the FDA and the Department of Veterans Affairs, a future where patients can find solace from pain without compromising their well-being is hopefully within reach. As the world embraces these exciting developments, we stand poised on the cusp of a transformative era in pain medicine—a future where compassion, innovation, and improved patient outcomes can converge.

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The Tulane Medicine team, who is also the Tulane Digest Team, is partnering at BIO 2023 this week. You can send a request through the BIO partnering system, or email us directly to arrange a time to connect.

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Curated Research and Research-Related News Summaries, Analyses, and Syntheses. Published on behalf of The Tulane University School of Medicine. Content is generated by reviewing scientific papers and preprints, reputable media articles, and scientific news outlets. We aim to communicate the most current and relevant scientific, clinical, and public health information to the Tulane community – which, in keeping with Tulane’s motto, “Not for Oneself but for One’s Own”, is shared with the entire world.

Kaylynn J. Genemaras, PhD: Editor-in-Chief

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Special thanks to James Zanewicz, JD, LLM, RTTP, and Elaine Hamm, PhD, for copyediting assistance