How Stem Cells Can Reverse Opioid Tolerance - Iffie Okoronkwo, M

How Stem Cells Can Reverse Opioid Tolerance

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On January 10, Pennsylvania Governor Tom Wolf declared a disaster emergency to fight the scourge of heroin and opioid abuse in his state, which has one of the highest overdose rates in the country.

“Pennsylvania’s opioid crisis impacts all areas of the state – including urban, suburban and rural communities and all ages including both young people and older Pennsylvanians – and is unprejudiced in its reach and devastation,” the declaration says. Virginia and other states have issued similar declarations.

Gov. Wolf’s effort comes five months after President Trump declared the opioid crisis a national public health emergency and two months after the president’s opioid commission released its final report, recommending more federal funding for addiction treatment, further restrictions on opioid prescribing, and the development of new non-opioid painkillers.

However, the commission’s report spent little time discussing an issue that is key to confronting the problems of opioid addiction and overdose – opioid tolerance. “Tolerance” is defined as a decrease in effect following repeated or prolonged use of a drug, which can result in the need for higher and higher doses to achieve the same result. For patients suffering from acute or chronic pain, this means that they need more pills to alleviate their pain.

Opioid tolerance can lead to a dangerous cascade of consequences. According to researchers at the National Institutes of Health, “the repeated administration of any opioid almost inevitably results in the development of tolerance and physical dependence.”

Although not all who become opioid tolerant become addicted, the World Health Organization asserts that people dependent on opioids are the group most likely to suffer an overdose. Given the seriousness of the problem, researchers have been looking for a way to prevent opioid tolerance and keep opioid users in a state of analgesia. In that quest, some have found an answer in stem cells.

In a recent study, Dr. Jianguo Cheng and scientists at the Cleveland Clinic and the Affiliated Hospital of Qingdao University in China hypothesized that mesenchymal stem cells (MSCs) could prevent or reverse opioid tolerance and opioid-induced hyperalgesia because of their profound anti-inflammatory properties.

To prove their hypothesis, they induced opioid tolerance in laboratory mice and rats by injecting them with morphine for four weeks. Astoundingly, after administering MSC therapy to the opioid-tolerant rodents, tolerance was reversed within as little as 2 days. The injections appeared to be completely safe. All of the rodents showed normal movement, food and fluid intake, and body weight gain. Their livers, kidneys and other major organs continued to function normally.

The authors concluded that MSCs have “enormous potential to profoundly impact clinical practice and improve opioid efficacy and safety.” Their study builds on previous research that found MSC therapy “does not produce unwanted side effects and is well tolerated and safe.” Rejection of the stem cells was not an issue because MSCs are immune-privileged.

America’s opioid problem is as destructive as ever. If the states and the president’s commission truly seek novel, innovative and readily-implementable solutions to the opioid crisis, tolerance is a critical target and stem cell therapy may be a viable solution. Patients in pain need solutions now.


Iffie Okoronkwo, M.D. is a Spine and Sports Rehabilitation Medicine and Pain Management physician at Manhattan Spine and Sports Medicine (, a private practice based in New York City with 40 years of experience providing the finest expert medical care and services to patients around the world.

Dr. Iffie is board certified in Physical Medicine and Rehabilitation and, as a physiatrist, utilizes ultrasound guided injections, fluoroscopy guided injections, PRP, regenerative medicine, and more to evaluate and treat a variety of conditions affecting muscles, joints, ligaments, and nerves.