Fentanyl

April 1, 2026 -- Researchers at the National Institutes of Health (NIH) have identified a novel, highly potent opioid that shows potential as a therapy for both pain and opioid use disorder. In a study published in Nature, the team observed the new drug’s effect in laboratory animals. They showed that it has high pain-relieving effects without causing respiratory depression, tolerance or other indicators of potential for addiction in humans. Positive safety profile of novel drug compound is surprise for class of synthetic opioids shelved years ago. “Opioid pain medications are essential for medical purposes, but can lead to addiction and overdose,” said Nora D. Volkow, M.D., director of NIH’s National Institute on Drug Abuse (NIDA). “Developing a highly effective pain medication without these drawbacks would have enormous public health benefits.” The team investigated formulations of an understudied class of synthetic opioid compounds, known as nitazenes. Nitazenes selectively engage mu-opioid receptors, primary targets for opioid drugs in the brain and peripheral nervous system. However, nitazenes had been shelved in the 1950s due to their excessive potency. The scientific team revisited this class of compounds with a focus on harnessing their selectivity for the mu opioid receptor and engineering new nitazenes with a safer pharmacological profile. “Our goal was to study the profile, or pharmacology, of these drugs,” said Michael Michaelides, Ph.D., senior author and NIDA investigator. “We wanted to decrease the potency and create a potential therapeutic. What we discovered exceeded our expectations.” The team focused initially on a chemical formulation called FNZ that could be administered to rats and tagged with a radioisotope for positron emission tomography (PET). PET imaging enables tracking of the drug in real time throughout the rat brain. The team discovered that FNZ entered the brain only briefly, for approximately five to 10 minutes. Yet pain relief, known as analgesia, persisted for at least two hours. Knowing that nitazenes can have active metabolites, or by-products, the team investigated whether an FNZ metabolite might be responsible for the prolonged effect. That investigation revealed DFNZ, another opioid dubbed a “superagonist” for its extremely high efficacy at the mu opioid receptor. Whereas FNZ carries serious risks, including depressed breathing and high potential for addiction, DFNZ appears to sidestep these liabilities. At preclinical therapeutic doses, DFNZ produced a moderate and sustained increase in brain oxygen rather than depressing respiration. Repeated doses of the drug did not result in tolerance, drug dependency, or meaningful withdrawal effects. Among 14 classic opioid withdrawal symptoms, the researchers only observed irritability, as measured by vocalization, when handling DFNZ-treated rats. To test the drug’s rewarding effects, an important component of their addictive potential, the team studied its effects in rats who had been trained to press a lever for a dose of the pain-relieving drug. They found that animals readily self-administered DFNZ, indicating that it does produce some rewarding effect. However, when the drug was replaced with saline, animals stopped the drug-seeking behavior. The immediate behavior change is in contrast with what researchers see with other opioids such as heroin, morphine, and fentanyl. In those cases, animals typically persist in seeking the drug even after it is removed. Further investigation revealed a likely neurochemical explanation. While DFNZ increases slow-acting dopamine release in the brain's reward circuitry, it does not trigger the rapid dopamine bursts associated with the formation of strong drug-cue associations, the conditioned responses that drive craving and relapse in addiction. “DFNZ has an unprecedented pharmacology for an opioid,” Michaelides said. “It is a potent and high-efficacy analgesic, but in certain contexts it resembles partial agonists, drugs that activate the receptor with low efficacy, which is what scientists think is needed for safety. Its capacity to be administered at therapeutic doses without producing respiratory depression is very important." The teams’ findings challenge the prevailing view that high-efficacy mu-opioid receptor drugs are unsuitable for development as safe analgesics. In fact, the authors of the paper maintain that DFNZ should be explored for use in treatment for opioid use disorder and may be preferable to current opioid agonist medications, which have an associated risk of causing respiratory depression. The research team will pursue additional preclinical studies to support an application for regulatory approval to conduct studies of DFNZ in humans. They believe several patient populations may benefit from DFNZ, including those in surgical settings and with cancer-related or chronic pain who have a particularly high need for effective pain treatment. This research was supported in part by the NIH Intramural Research Program and by NIH/NIDA grant DA056354. About the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. For more information about NIDA and its programs, visit www.nida.nih.gov. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. NIH…Turning Discovery Into Health ® Michaelides M., Rice K., Skiniotis G., et al. A μ opioid receptor superagonist analgesic with minimal adverse effects. Nature. 2026. DOI: 10.1038/s41586-026-10299-9 . Source: NIH

Vancouver, British Columbia--(News - March 30, 2026) - PreveCeutical Medical Inc. (CSE: PREV) (OTCQB: PRVCF) (FSE: 18H0) (" PreveCeutical " or the " Company "), a health sciences company that develops innovative options for preventive and curative therapies utilizing organic and nature-identical products, is pleased to announce the appointment of Dr. Raj S. Pruthi, MD, MHA, FACS, to its Board of Directors. Dr. Pruthi is an accomplished physician-scientist and executive with more than 20 years of experience spanning academic medicine, global pharmaceutical leadership, and biotechnology innovation. In his new role, he will contribute to shaping the Company's clinical development strategy and advancing key initiatives, including its Sol-gel program, Nature Identical™ peptide platform, non-addictive pain management therapies, and dopamine-based treatments targeting Parkinson's disease. Bringing extensive experience in clinical trial design, regulatory strategy, and organizational leadership, Dr. Pruthi has worked closely with global regulatory agencies such as the FDA and EMA and has been actively involved in capital markets initiatives. He currently serves as Chief Medical Officer of Relmada Therapeutics, Inc., a position he has held since June 2025. There, he leads development of the NDV-011 bladder cancer program, including a Phase 2 study and preparations for a global Phase 3 registrational trial expected to commence in early 2026. His responsibilities have included stakeholder engagement, trial execution, and collaboration with investors and regulatory authorities. He also played a central role in financing efforts that generated over $100 million through a public offering and an additional $160 million via a PIPE transaction. From 2022 to 2024, he held senior leadership roles in oncology at Johnson & Johnson Innovative Medicine (Janssen), where he contributed to late-stage clinical development, including multiple Phase 3 trials and regulatory submissions. His work supported approvals from both the FDA and EMA, including the approval of TAR-200 in 2025 for certain bladder cancer patients. He also incorporated patient-reported outcomes and digital health tools into clinical study designs. Before transitioning to industry, Dr. Pruthi spent over two decades in academia, serving as a tenured professor and Chair of Urology at leading institutions such as the University of California, San Francisco and the University of North Carolina. He is recognized for pioneering robotic surgical techniques and has shared his expertise internationally. His academic record includes more than 220 peer-reviewed publications, numerous book chapters, and hundreds of scientific presentations, along with leadership roles in national clinical guideline development. Dr. Pruthi received his medical degree from Duke University, completed his surgical and urology training at Stanford University, and earned a Master of Health Administration from the University of North Carolina at Chapel Hill. He is board-certified in urology and a Fellow of the American College of Surgeons. "I am excited to join PreveCeutical at an important stage of its evolution," said Dr. Pruthi. "The Company's commitment to developing innovative therapies based on natural and nature-identical compounds aligns closely with my professional interests. I look forward to working with the team to advance its clinical programs and address significant unmet medical needs." Stephen Van Deventer, Chairman and CEO of PreveCeutical, added: "We are very pleased to welcome Dr. Pruthi to our Board. His extensive experience in clinical development, regulatory strategy, and leadership will be invaluable as we continue to advance our pipeline. His expertise strengthens our ability to deliver innovative therapies and achieve meaningful progress across our programs." About PreveCeutical Medical Inc. PreveCeutical is a health sciences company that develops innovative options for preventive and curative therapies utilizing organic and nature identical products. PreveCeutical aims to be a leader in preventive health sciences and currently has five research and development programs, including: dual gene therapy for curative and prevention therapies for diabetes and obesity; the Sol-gel Program; Nature Identical™ peptides for treatment of various ailments; nonaddictive analgesic peptides as a replacement to the highly addictive analgesics such as morphine, fentanyl and oxycodone; and a therapeutic product for treating athletes who suffer from concussions (mild traumatic brain injury). For more information about PreveCeutical, please visit our website or follow us on Twitter and Facebook . On Behalf of the Board of Directors, PreveCeutical Medical Inc. " Stephen Van Deventer" Chairman & Chief Executive Officer For further information, please contact: Stephen Van Deventer (604) 306-9669 info@PreveCeutical.com Forward-Looking Statements: This news release contains forward-looking statements and forward-looking information (collectively, "forward-looking statements") within the meaning of applicable Canadian and U.S. securities legislation, including the United States Private Securities Litigation Reform Act of 1995. All statements in this news release that are not purely historical are forward-looking statements and include any statements regarding beliefs, plans, expectations and orientations regarding the future, including, without limitation, the continued research interests of PreveCeutical, PreveCeutical's anticipated business plans, and its prospects of success in executing its proposed plans. Often, but not always, forward-looking statements can be identified by words such as "will", "pro forma", "plans", "expects", "may", "should", "budget", "schedules", "estimates", "forecasts", "intends", "anticipates", "believes", "potential", "proposes" or variations of such words including negative variations thereof and phrases that refer to certain actions, events or results that may, could, would, might or will occur or be taken or achieved. Forward-looking statements are based on certain assumptions regarding PreveCeutical, including expected growth, results of operations, including PreveCeutical's research and development activities, performance, industry trends, growth opportunities, that PreveCeutical will be granted requisite expedited approvals by world health, retain and attract qualified research personnel and obtain and/or maintain the necessary intellectual property rights needed to carry out future business activities. Actual results could differ from those projected in any forward-looking statements due to numerous factors including, risks and uncertainties relating to: complexities and delays in connection with research and development activities and the actual results of research and development activities; the ability of PreveCeutical to, among other things, protect its respective intellectual property, obtain any required governmental, regulatory or stock exchange approvals, permits, consents or authorizations required, including Canadian Securities Exchange acceptance of any planned future activities and obtaining expedited requisite approvals from world health agencies; and the ability of PreveCeutical to commercialize products, pursue business partnerships, complete their research programs as planned, and obtain the financing required to carry out their planned future activities. Other factors such as general economic, market or business conditions or changes in laws, regulations and policies affecting the biotechnology or pharmaceutical industry may also adversely affect the future results or performance of PreveCeutical. These forward-looking statements are made as of the date of this news release and, unless required by applicable law, PreveCeutical assumes no obligation to update the forward-looking statements or to update the reasons why actual results could differ from those projected in these forward-looking statements. Although PreveCeutical believes that the statements, beliefs, plans, expectations, and intentions contained in this news release are reasonable, there can be no assurance that those statements, beliefs, plans, expectations, or intentions will prove to be accurate. Readers should consider all of the information set forth herein and should also refer to other periodic reports provided by PreveCeutical from time-to-time. These reports and PreveCeutical's filings are available at . Neither the Canadian Securities Exchange (CSE or CNSX Markets), its Regulation Services Provider (as that term is defined in policies of the CSE), nor any other regulatory authority accepts responsibility for the adequacy or accuracy of this release. Any link in this press release to external information or other resources is provided for reference only, and such information or resources might change from time to time, and may include forward-looking statements as described above, and are subject to the above disclaimers under this heading forward-looking statements. Readers are cautioned that forward-looking statements are not guarantees of future performance or events and, accordingly, are cautioned not to put undue reliance on forward-looking statements due to the inherent uncertainty of such statements. To view the source version of this press release, please visit