It’s Time to Talk About Fentanyls, Plural

By Roger Chriss, PNN Columnist

The U.S. overdose crisis saw over 100,000 deaths in the year ending May 2021, driven primarily by illicitly produced fentanyl. But fentanyl is both a specific drug and a class of drugs, a distinction that is not always appreciated or understood.

At a December 2 meeting of the House Energy and Commerce’s Subcommittee on Health, Rep. Anna Eshoo (D-CA) was puzzled by testimony calling for more research into fentanyl and its chemical cousins, known as analogues.

“I don’t quite understand the need to study fentanyl, we already know what it does. It is not clear to me. Everyone has stated how devastating fentanyl is,” said Eschoo. “What is it that we don’t know about this?”

In fact, a great deal is unknown about the fentanyls causing overdoses, including their potency and potential drug interactions. As the National Institute on Drug Abuse explains, there are 15 to 30 different fentanyl analogues, including acetylfentanil, carfentanil and furanofentanyl, each with its own potency.

Fentanyl itself was first synthesized in 1959 by Paul Janssen. It entered medical use in 1968 in the form of fentanyl citrate as a general anesthetic, and has since been used in chronic pain, palliative care and combat medicine.

The two other common pharmaceutical fentanyls are sufentanil and remifentanil. The former was first synthesized in 1974 and the latter was developed in the early 1990s. Sufentanil is the most potent prescription opioid currently available, and is the only one strong enough to displace buprenorphine and provide analgesia. Remifentanil, by contrast, has a faster onset and recovery time.

But these are not the fentanyls appearing in most drug deaths, which are known collectively as illicitly manufactured fentanyl (IMF) or clandestine fentanyl. Such drugs have a substantial chemical similarity to pharmaceutical fentanyls, going by names like 4-fluoroisobutyryl fentanyl, lofentanyl and valeryl fentanyl.

Each fentanyl has its own characteristics. For instance, a new study of 13 fatal overdoses in Michigan involving valeryl fentanyl found that blood samples from the same decedent tested both positive and negative for the drug. This indicates that valeryl fentanyl has unique pharmacokinetics, which could make it more difficult for medical examiners to detect in overdose cases.

Similarly, a recent study in Psychopharmacology on a fentanyl analog called cyclopropylfentanyl found that when the drug was given to rats it “displays much greater analgesic potency when compared to morphine, suggesting that cyclopropylfentanyl poses increased overdose risk for unsuspecting users.”

Fentanyl’s ‘Evil Cousin’

But in many cases, the lethal dose of an illicit fentanyl can only be guessed at. As Josh Bloom recently explained in the American Council on Science and Health, fentanyl’s “evil cousin” mefentanyl may be 35 times more potent than prescription fentanyl. Even worse, standard test strips for fentanyl are only modestly effective in detecting mefentanyl,

“It's a damn good thing that mefentanyl isn't one of the common fentanyls pouring into this country,” wrote Bloom. “Imagine if a much more potent analog of fentanyl (was) widely circulating in the US with no way to detect it preemptively. Nightmare.”

Further, how fentanyls combine with other drugs requires investigation. For instance, a recent report of a person smoking a drug mixture that combined a potent fentanyl analog with a psychostimulant suggests that drug traffickers are creating new designer drugs to reduce the risk of their customers dying from respiratory depression.

Some fentanyls are so potent and chemically complex that higher doses of the overdose reversing drug naloxone are needed. A new study in the International Journal of Pharmaceutics suggests that naloxone may have to be modified to work better against illicit fentanyls. The study authors are working on a derivative of naloxone named NX-90 that may have a better pharmacological profile.

So this is why the plural is essential. We need to know as much as possible about pharmaceutical fentanyl and its chemical cousins remifentanil and sufentanil in order to improve clinical care. And we need to know as much as possible about illicit fentanyls in order to detect them accurately and develop better overdose rescue drugs.

Last, we need to keep an eye out for new synthetic opioids like protonitazene and isotonitazene, which are emerging regularly and are even more potent than fentanyl.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research. 

Little Evidence Opioid Use by Children Leads to Addiction

By Pat Anson, PNN Editor

Healthcare providers have become more cautious in recent years about giving opioid pain medication to children, fearing that even short-term use could lead to a lifetime of addiction or even a fatal overdose.

But in a review at the University of Alberta, pediatric researchers found little evidence to support a link between short-term opioid use in childhood and opioid use disorder (OUD) later in life.

“We actually didn’t find a lot of evidence to directly answer our question,” said senior author Michele Dyson, PhD, assistant professor of pediatrics in the Faculty of Medicine & Dentistry and associate director of the Alberta Research Centre for Health Evidence.

“If opioids are used as indicated, they can be a safe and effective strategy for pain management,” she said. “In some cases, they really are part of the best treatment plan to manage a child’s pain.”

Dyson and her colleagues reviewed 21 observational studies involving nearly 50 million patients under the age of 18 who were exposed to opioids for less than 14 days. Most of the studies were considered low quality and did not look at the duration of opioid use.

One study did show a potential link between short-term exposure and later abuse. But researchers concluded the findings overall were not definitive because they did not specify duration of exposure or lacked a control group. Their findings are reported in the journal Pediatrics.

“There is limited evidence to determine if short-term therapeutic exposure to opioids in childhood is
definitively associated with future nonmedical opioid use or development of an OUD; however, this review suggests a link between lifetime therapeutic opioid use (unknown duration) and nonmedical opioid use. The existing evidence on risk factors for nonmedical opioid use or OUD after short-term therapeutic exposure is unclear,” researchers concluded.

Conflicting Advice

Whether opioid medication is appropriate for children is a controversial issue. Earlier this year, the World Health Organization (WHO) released new guidelines recommending that opioids only be used for children who are dying or seriously ill and not expected to recover.

Like the Alberta study, a WHO advisory panel found little good quality research on how to treat childhood pain, but recommended that children with chronic pain be treated with physical therapy and psychological interventions such as cognitive behavioral therapy.  

An international study in The Lancet came to a very different conclusion, warning that opioid prescribing guidelines intended for adults are being “inappropriately applied to young people.” Because of the stigma associated with opioids, researchers said childhood pain was often untreated or poorly treated, leading to chronic pain, disability and other negative consequences in adulthood.

“Health-care professionals, young people, and parents continue to hold misconceptions and believe myths about opioid use in pediatric patients, whereby the media depicts opioids as the villain and the underlying reason for substance misuse,” researchers said. “Opioids have their place in pediatric pain medicine.”

That finding is at odds with a 2018 warning from the U.S. Food and Drug Administration, which said that cough and cold medications containing opioids pose “serious risks” to children and should no longer be prescribed to patients younger than 18.

A recent study found that opioid misuse is relatively rare in U.S. adolescents and young adults. Less than 1% of those who filled an opioid prescription for the first time overdosed or developed opioid use disorder within the next 12 months.

The conflicting advice can be confusing to both parents and providers.

“Parents see stories about overdoses in the news and are afraid for their children, while physicians and prescribers are also worried because they don’t know what the evidence is,” says Dyson. “Health-care providers don’t want to cause harm, and at the same time, they still want to be able to treat pain appropriately.”

Dyson and her team at the University of Alberta have developed a series of infographics to help physicians, parents and young people recognize that opioid pain relievers are sometimes needed.

One such graphic plainly states: “Opioids don’t have to be scary!”

View fullsize

UNIVERSITY OF ALBERTA INFOGRAPHIC

“While we can’t say for sure that a short-term prescription for pain is linked with misuse, there is some evidence that that could happen,” she explained. “There is likely some risk, but it needs to be balanced with the harms of stigmatizing opioid use and under-treating pain, which comes with its own significant short- and long-term consequences.”

Are You in Palliative or Curative Care?

By Dr. Forest Tennant, PNN Columnist

If you are in medical treatment for a chronic disease, you are either in curative or palliative care. Every patient with intractable pain syndrome (IPS), their family and physicians need to be very clear as to which category they are in.

A major reason that IPS patients can’t get the help they need is because they have not made the determination and been declared to be in palliative care. If you are not in palliative care, you may be restricted from obtaining certain drugs, dosages and financial benefits you need for your well-being. 

What is Curative Care?

Curative care is treatment that is focused on resolving a specific disease or disorder that is causing symptoms such as pain, fatigue, depression or physical impairments. Treatment can be directed either at total or partial cure of the disease or disorder.

What is Palliative Care?

Palliative care is symptomatic treatment to provide relief and quality of life to someone with an incurable condition. Palliative care will also hopefully prevent an incurable disease or disorder from worsening and causing further complications.

There are two reference books published for physicians so they can quickly look up the latest on diagnosis and treatment.  Their definitions of palliative care are given here to help all parties know which care -- palliative or curative --- best fits any given patient.

“Palliative care is medical care focused on improving quality of life for people living with serious illness. Serious illness is defined as a condition that carries a high risk of mortality, negatively impacts quality of life and daily function and/or is burdensome in symptoms, treatments and caregiver stress.” -- Current Medical Diagnosis and Treatment

“Palliative care is treatment that is focused on pain and symptom management as well as quality of life for patients and their families. It can be rendered at any point in the course of treatment of illness, whether that illness is life threatening or not.” – Current Therapy

The World Health Organization defines palliative care as “prevention and relief of suffering in adults or pediatric patients and their families facing the problems associated with life-threatening illness.”

Misconceptions About Palliative Care

There are many misconceptions about what qualifies a patient to be palliative care. Here are just some of the common misconceptions and fallacies:

• Must be at “end-of-life.” No! An incurable disease may occur at any age.

• Must be in a hospice. No!

• Must be on Medicare. No!

• Must be in a nursing home, assisted living or hospital. No!

• Must have cancer. No! Palliative care applies to any incurable disease.

• Must enroll in a program called “palliative” or with a “palliative care organization.” No!

• Must go to a doctor who specializes in palliative care. No!

• Palliative care requires the patient to have a permit or certificate. No!

Even though there are some physicians and programs that specialize in palliative care, any MD or DO can declare a patient to be “palliative” and provide the necessary medication for relief of pain and other symptoms.

You may have to be declared to be in “palliative care” and have it stated in your medical record, so that you can obtain the medications and dosages to adequately relieve your pain. Federal guidelines specifically exempt palliative care patients from a recommendation that daily opioid doses not exceed 90 milligrams morphine equivalence (MME). If you have not been declared to be in palliative care and it isn’t in your medical record, your opioid dosage may be reduced. 

Presenting Your Case for Palliative Care

In order to obtain proper care and necessary medications in today’s healthcare system, you will likely need to be declared “palliative” by one of your personal physicians. This declaration will need to be recorded in your medical record and all concerned parties informed of it. Your pharmacy, insurer, laboratory and other healthcare providers should all be told that you are in palliative care.  

Most IPS patients need palliative care and meet the necessary requirements to be declared as palliative. One of your doctors needs to simply write into your medical record the name of your incurable disease, and that your treatment will focus on symptom management, comfort and quality of life. There is no requirement to state how long you may live.

The only required documentation is a written chart note in your medical record by a licensed physician in your state. They will need to state the specific name of your incurable disease and that you are in palliative care.

Every IPS patient and family needs to determine whether their treatment needs to be palliative or curative.  While everyone would like a cure, this may not be practical or possible.  What evidence or experience tells you that you can achieve a cure?  It may be depressing to recognize that a complete cure is not possible, but you must face reality.

Keep in mind that an incurable disease and pain doesn’t have to keep you from having a meaningful, productive and good quality of life. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here. The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Stem Cells Could Help Diabetics Produce Their Own Insulin

By Pat Anson, PNN Editor

With insulin prices soaring out-of-reach for many U.S. patients, there’s hope on the horizon for people with Type 1 diabetes. Researchers are making significant progress in developing stem cell therapies that could restore their ability to produce their own insulin.

Interim findings from two early stage clinical trials, published today in the journals Cell Stem Cell and Cell Reports Medicine, show that pancreatic endoderm cells derived from human pluripotent stem cells (PSCs) began producing insulin in diabetic patients within months of being implanted in a tiny device under the skin.

While the amount of insulin secreted by the cells was not enough to cure Type 1 diabetes, they were sufficient enough to reduce the insulin requirements of some patients by as much as 20% and increase the amount of time spent in their targeted blood glucose range. Both studies showed that the stem cells can survive up to 59 weeks after implantation.

"A landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes," says Eelco de Koning, MD, of Leiden University Medical Center in the Netherlands, who co-authored a commentary published in Cell Stem Cell. "Despite the absence of relevant clinical effects, this study will remain an important milestone for the field of human PSC-derived cell replacement therapies as it is one of the first to report cell survival and functionality one year after transplantation."

There are a number of caveats here. Less than three dozen patients participated in the Phase 1/2 studies, the outcomes were highly variable, and there were no control groups to compare the results with. The implanted stem cells were also derived from donors – meaning the patients had to take immunosuppressive drugs to prevent their bodies from rejecting the implants, leaving them vulnerable to infections. At least two patients experienced serious adverse events associated with having their immune systems suppressed.

Researchers still need to determine at what stage the stem cells are optimal for transplantation and the best place to implant them. It is also not clear how long the cells remain effective and whether the need for immunosuppressive therapy can be eliminated.

But the studies demonstrate that stem cells can mimic the insulin-producing pancreas cells that diabetics lack.

“A landmark has been set. The possibility of an unlimited supply of insulin-producing cells gives hope to people living with type 1 diabetes.”

— Eelco de Koning, MD

"The clinical road to wide implementation of stem cell-derived islet replacement therapy for type 1 diabetes is likely to be long and winding,” de Koning says. "But an era of clinical application of innovative stem-cell based islet replacement therapy for the treatment of diabetes has finally begun."    

About 460 million people worldwide have diabetes mellitus, a disorder in which the body does not produce enough insulin, causing blood sugar (glucose) levels to be abnormally high.  In Type 1 diabetes, the body’s immune system attacks the insulin producing cells of the pancreas. Left untreated, diabetes damages blood vessels and significantly raises the risk of stroke, heart attack and diabetic neuropathy.

Diet, exercise and regular insulin injections can help control Type 1 diabetes. But with insulin selling for about $300 a vial in the United States – 10 times more than in other developed countries --  some diabetics have rationed or even stopped taking the life-saving injections.

Another encouraging stem cell study -- involving just one patient -- was recently reported by Vertex Pharmaceuticals. A chronically ill man with Type 1 diabetes who has been taking insulin injections for decades – up to 34 units per day – began producing his own insulin after being injected with an experimental stem cell product called VX-880.

As a test, researchers only injected him with about half the targeted amount of VX-880, but within 90 days the man had reduced his need for insulin injections by 91 percent.

“These results from the first patient treated with VX-880 are unprecedented. What makes these results truly remarkable is that they were achieved with treatment at half the target dose,” Bastiano Sanna, PhD, Executive Vice President of Vertex, said in a statement. “While still early, these results support the continued progression of our VX-880 clinical studies, as well as future studies using our encapsulated islet cells, which hold the potential to be used without the need for immunosuppression.”

Vertex plans to expand the study to eventually include up to 17 patients, at multiple sites in the U.S. and Canada.

Patients and Doctors Finally Talking About Medical Cannabis

By Pat Anson, PNN Editor

Communication is important in every relationship, especially between doctors and patients. And a new survey suggests that the stigma that has long kept cannabis a dirty secret in the exam room may finally be disappearing.   

The survey of 445 healthcare providers who treat chronic pain found that 72% of them have patients who requested or asked about medical cannabis in the last 30 days. Patients asked about cannabis far more often than other alternative pain treatments, such as acupuncture (37%), physical therapy (13%) and massage (10%).

The online survey was recently conducted by Cannaceutica, a healthcare company developing a line of cannabis products to treat pain. A variety of providers participated in the survey, including general practitioners, pain management specialists, neurologists, rheumatologists, and nurse practitioners.

People weren’t always so willing to talk to healthcare providers about cannabis, fearing they’d be seen as pot heads or even be dropped as patients. National surveys conducted in 2018 and 2019 found that less than 40% of patients told their doctors about their cannabis use.  

More patients are talking about cannabis today, and more doctors are willing to listen. The vast majority of providers (81%) in the Cannaceutica survey believe cannabis will play a role in the future management of chronic pain, but only one in four are likely to recommend it now. The primary factors holding them back are legal and regulatory issues, and the lack of good quality cannabis research.

Medical cannabis is legal in 36 states, but remains illegal at the federal level. If cannabis were legalized federally, 74% of providers said they would be likely to recommend it to a patient.

To increase their comfort level about recommending cannabis, providers want to see more research and documentation about cannabis as a pain treatment. Nearly two-thirds (64%) said patients were their main source of information about cannabis, followed by the internet (44%) and medical journals (40%).

Over half the providers surveyed said current treatment options are insufficient to treat chronic pain (56%) and that they were actively seeking alternatives (58%) for their patients. It’s worth noting that pain management specialists were most likely to say current treatments are inadequate (59%) and that they were seeking alternative treatments (66%).  

Clinical Trial Seeks Volunteers

Cannaceutica is currently enrolling chronic pain patients in a clinical trial to test the safety and efficacy of its cannabis capsules, which contain a blend of tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as the cannabinoids cannabichromene (CBC) and cannabigerol (CBG). A recent study found that CBG boosts the potency of cannabis products used to treat chronic pain, depression, insomnia and anxiety.

The observational study is being led by University of California, Irvine researcher Dr. Marcela Dominguez. She and her team hope to enroll 107 patients in the trial, which is expected to last 14 to 16 weeks. They’re looking for people who have experienced pain for at least three months, have tried at least two different medications, and are not currently using cannabis. Patients with fibromyalgia or cancer pain are not eligible to participate.

If you would like to volunteer or get more information in the study, click here.

Rare Disease Spotlight: Valley Fever

By Barby Ingle, PNN Columnist 

As the final article in my series on rare diseases, I am going to cover something that has been impacting my life for the past 2 years and 25 days – coccidioidomycosis --- otherwise known as Valley fever. This is a health challenge that has been difficult and longer lasting than typical for a patient like me. I have headaches, chest pain and feel exhausted.

Tests show that I am still positive for Valley fever, both the active fungal infection and the antibodies my body produces to fight it. Over the past few weeks, I feel more pressure in my lungs, as if Valley fever pneumonia is returning. I am more exhausted than ever and have skin blisters again. I liken them to shingles, as I have had them multiple times over the past few years and it usually happens during periods of stress.

I took an antiviral, but maybe it is the Valley fever that is showing itself again as my breathing decreases. I can tell this by feel, as well as testing my blood oxygen levels and heart rate hourly over the past week. My coughing and shortness of breath have also increased.

Is this a new exposure or just the same old, same old? I have a close family member going through Covid currently and have been extremely careful not to get it, but I wonder. I have been tested for Covid 5 times now over the past 2 weeks with 3 home tests, a rapid test and a PCR test. All of these were negative, for which I thank God. But the symptoms of Covid and Valley fever seem to be similar.  

BARBY INGLE

When I first got the Valley fever in 2019, PNN did an article about what I was going through and the growing number of cases in the Southwest. Little did I know I would still be dealing with Valley fever more than 2 years later.

My lung specialist told me it would take about one year to get over it. The variable we did not know at that time was that I was allergic to the one medication that is invented specifically for coccidioidomycosis.

Since my diagnosis, I have been extremely tired -- more than I was with any of the other chronic and rare diseases I live with. I do not know if this is a new infection or if my immune system is compromised by all that I live with. I do know I am tired. All of the time.

It has also put my thinking and ability to handle pain into a new view. I am now very mindful of my breathing, getting oxygen appropriately, and any tingling sensations. That is the feeling I get when my oxygen levels are low. I used to worry more about the burning fire pain from RSD. That is still there and is constant, too. However, if I can’t breathe, the pain doesn’t matter as I won’t be able to live. 

How does one get coccidioidomycosis? The coccidioides fungus that causes it is found in soil of the desert Southwest and causes infection when inhaled. You can get it simply by breathing in microscopic fungus spores. Even our pets, especially dogs, can get Valley fever. It is not passed from human to human, although if you breathe the same air, you may see a cluster of people with it.

My husband Ken was tested for Valley fever after I developed it. His lungs show that he did have it, though he has a great immune system and showed no signs or symptoms. His body just beat it.

For people like me with suppressed immune systems, the risk is high for complications and severe symptoms if we become infected. I was actually misdiagnosed at first because Valley fever does resemble a flu with fever, cough, chills and chest pain. Once it turned into pneumonia and I was treated for a bacterial infection, it was figured out.

Ironically, my lung specialist thought that Ken and I probably got it from driving with the car windows down for fresh air. Valley fever cases spike when summer monsoons hit and cause dirt devils, and after earthquakes when fungal spores are kicked up into the atmosphere.

Worldwide and nationally, Valley fever is considered a rare condition. But in the U.S. Southwest and northern Mexico it is more common. If you are visiting the Southwest or live here, it is a condition you should know about and understand. The sooner you can take action against it or not be exposed to it, the better. Arizona, where I live, accounts for about two-thirds of the cases each year.   

Most infections last for a few weeks or months, but some patients like me can have symptoms that last longer. Because I experienced such a severe case at the start, I have long-term damage in my lungs and will likely continue to have challenges with my breathing and energy.  

I hope that you have enjoyed my series on rare diseases and have found the information educational, useful and motivating. I would love if more people understood the 7,000 plus rare diseases just a little better. I still have a long way to go to understand and learn about them. I have only scratched the surface. It has given me a better understanding of the diversity in conditions, the similarities that patients with rare diseases experience, and an empathy for those fellow patients who I advocate for as often as I can.

Barby Ingle lives with reflex sympathetic dystrophy (RSD), migralepsy and endometriosis. Barby is a chronic pain educator, patient advocate, and president of the International Pain Foundation. She is also a motivational speaker and best-selling author on pain topics. More information about Barby can be found at her website.

A Promising Stem Cell Therapy for Back Pain

By Gabriella Kelly-Davies, PNN Columnist

Just before sunrise on Christmas Eve last year, a delivery van from our local fish market left a bulky box of fresh prawns, oysters and lobsters on our doorstep for Christmas Day celebrations.  

Sleepily bending over, I picked up the box, unaware it was packed to the brim with enormous blocks of ice to prevent the seafood from succumbing to Australia’s stifling summer heat. As I lifted the box from the doormat, I felt a sharp pain like an electric shock run down the back of my left leg and pins and needles explode in my left foot.  

Fast forward to now, and the pain and pins and needles sensation are constant, especially when I sit to write. Like millions of other people, I have chronic lower back pain, the leading cause of disability worldwide. And like them, I too want the pain to go away without surgery.  

Two weeks ago, my pain specialist injected cortisone into my spine, reducing the pain enough to allow me to sit for meals and do a little writing. But he warned I would most likely need surgery at some point. The neurosurgeon agreed, suggesting microdiscectomy was my only option.  

As a former physiotherapist, I know that a lumbar discectomy can relieve the symptoms of nerve compression, but it doesn’t reverse the underlying degeneration of the intervertebral disc. This is why up to one third of patients continue to experience back pain after surgery and some require further operations.

In my search for non-surgical treatments, I read an article about Australian research that has led to the development of a new stem cell therapy to treat back pain. Professor Tony Goldschlager, who leads the study, is a neurosurgeon who advocates for the use of minimally invasive spinal surgery. He heads up a research team at Monash University in Melbourne that is part of the Monash Health Translation Precinct (MHTP).  

Goldschlager started his stem cell research 15 years ago. He and his team developed the stem cell therapy in the laboratory, then spent years testing it in preclinical models. The results of several studies revealed that the therapy was safe and effective. After completing these studies, the researchers began human clinical trials, testing the ability of stem cells to regenerate the intervertebral disc and reduce back pain.  

“We’ve had success both in preclinical and clinical studies of being able to restore structure and function of the disc,” Goldschlager told me. “This reduces pain and improves quality of life for patients.” 

Phase Two clinical trials saw a significant number of patients report reduced back pain for up to two years after a single injection. Phase Three trials are almost complete and while Goldschlager hasn’t received all the results from overseas studies, the data he has seen so far is promising. He is hopeful the new treatment— a single injection — will be available in two years after the final round of clinical trials concludes. 

“What excites me is that we might be able to prevent surgery all together and regenerate the disc. Most of the current treatments don’t address the underlying problem. But the stem cell injection reduces the inflammation and stimulates a regenerative process in the disc, removing the source of back pain. The stem cells can become new disc-like cells and replenish the damaged disc cells,” explained Goldschlager. 

During the last 15 years, Goldschlager and his team have published the results of their studies in peer-reviewed journals such as Spine, Nature Outlook and the Journal of Neurosurgery. In 2015, they published an extensive review of the use of stem cell therapies in lumbar disc disease. 

New Era in Medicine

While the use of stem cells heralds the dawn of an exciting new era in modern medicine, it also raises several ethical and safety concerns. Critics say many stem cell therapies are unproven, and others believe it is unethical to destroy human embryos during research or create new embryos specifically for research. 

Goldschlager is acutely aware of these concerns and in 2010 as a neurosurgery registrar, worked in a research team that published an article on the ethics of using stem cell therapies in patients with spinal cord injuries. He says the therapy his team has developed doesn’t raise ethical concerns because it is based on a proprietary adult stem cell technology from Mesoblast, an Australian biotechnology company.

The cells are derived from the bone marrow of healthy young adults who have given informed consent. Young adults are selected because the number of stem cells in our bodies reduce as we age. The cells of older people are also less effective at repairing damaged tissues and organs.

Commercial stem cell clinics usually harvest the fat, muscle or cartilage cells of their patients, process the cells in a centrifuge, then inject them back into the same patient’s body. This yields a mixed population of cells with a small and inconsistent number of stem cells. Adults of all ages are offered this treatment, even though it might not work for older patients because their stem cells are not as plentiful or robust as those of younger ones. These treatments can cost thousands of dollars, are often ineffective, and come with a heightened risk compared to a pure, tested proprietary off-the-shelf product.  

Another reason for caution is that some of the clinicians who provide stem cell treatments lack sufficient training and accreditation, increasing the risk of safety and efficacy issues. It is critically important for patients to check the qualifications of clinicians who offer stem cell therapies and to understand how the cells used at these clinics are created. The therapy should have been through rigorous clinical trials to demonstrate safety and efficacy.  

While new stem cell treatments offer hope to millions of people who live with degenerative spinal conditions, they are not a “miracle cure.” Still, I hope I’ll have the option of trying Professor Goldschlager’s technique once it is available.

Gabriella Kelly-Davies lives with chronic migraine.  She recently authored “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

People in Pain Fight What Others Can’t Understand

By Carol Levy, PNN Columnist

“We are so fond of one another, because our ailments are the same.” Jonathan Swift.

That does not apply to those of us with chronic or intractable pain. Our “ailments” are different. Very different. Painful conditions caused by genetics, trauma, medical error or sheer bad luck. Many healthy people don’t know such pain can exist.

In the 1980's, organ transplant rejection was thought to be psychological. Then they learned that it is not in the mind. It is the body doing the rejecting.

Forty years later, many doctors still believe chronic pain is in the psyche. Hopefully, more are accepting that the mind is involved in chronic pain and helps determine how we respond to it, but it’s not where the pain originates.

As difficult as it is for us to accept persistent pain and the resultant disabilities, it makes it even harder when doctors, family, friends and colleagues say, “Oh, c'mon. It's not that bad. You just think it is. So you can think it into being better.”

Mindfulness, relaxation techniques and meditation are helpful -- to the mind. They help some of us deal with the pain, but most still need the benefit of opioids and other pain medications, treatments and physical therapy.

“I don't want my pain and struggle to make me a victim. I want my battle to make me someone else's hero.” Unknown author.

How often do we hear that? First usually comes the praise: “You are a true pain warrior.” Then the gut punch: “Your pain and struggle are such a good example to others who suffer. You should be grateful. That’s why you have the pain, to be an example.”

I'm sorry, but I don't want to be in pain every day so someone else can learn from my fight. It is a nice side benefit, but it is not why I fight the pain.

Chronic pain does make us different from others. We talk about it a lot, online and elsewhere. Cancer, diabetes, heart disease and other well-known illnesses -- people know and understand them. But Ehlers Danlos, CRPS, trigeminal neuralgia, arachnoiditis and other names too long to list are still the stranger in the room.

It is a struggle for us every day. We fight what others can't and don't want to understand.  Because it is a feared ailment once they know it exists.

Our fight is with us at all times, in whatever we do or try to do. It is daunting.

“Promise me you'll always remember: You're braver than you believe, and stronger than you seem, and smarter than you think.” A.A. Milne

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.

12 Holiday Gifts on Living With Chronic Pain and Illness

By Pat Anson, PNN Editor

Would you like to know how to avoid paying for inflated medical bills? Where and how to find a good CBD pain reliever? What really killed Elvis Presley? And just who is Patient Z?

The answers to these and other questions can be found in our annual holiday gift guide. If you live with chronic pain or illness and want to have a friend or family member get a better understanding of what you're going through -- here are 12 books that would make great gifts over the holidays. Or you can always “gift” one to yourself.

Click on the book cover to see price and ordering information. PNN receives a small amount of the proceeds -- at no additional cost to you -- for orders placed through Amazon.

The Pain Gap by Anushay Hossain

Anushay Hossain nearly died during 30 hours of labor in a U.S. hospital, her pain so severe due to a botched epidural that she shook uncontrollably. An emergency C-section saved her and the baby. That traumatic experience led Hossain to write this book about sexism and racism in healthcare, in which she shares the real life stories of women who have been “dismissed to death” by medical neglect.

The Strange Medical Saga of Elvis Presley by Forest Tennant

Ever since Elvis Presley’s death in 1977 at the age of 42, rumors have persisted about what happened. Did Elvis die of a heart attack or drug overdose? Dr. Forest Tennant sets the record straight with an inside look at Presley’s chronic health problems, including the possibility that he had Ehlers Danlos syndrome, a connective tissue disease that made it easier for Elvis to gyrate and dance — but ultimately may have led to his early death.

All’s Well by Mona Awad

A novel about a frustrated actress whose career is cut short by chronic pain. She reinvents herself as a college theater director, only to find her student cast is openly skeptical about her pain. To get revenge, she finds ways for people who dismiss her pain to experience it for themselves. Written by best-selling author — and chronic pain sufferer — Mona Awad.

Chronically Empowered by Jessica Cassick

This book is a collection of inspirational short stories told by 65 artists, entrepreneurs and advocates who all live with a chronic illness. Each author describes how they struggled to overcome the adversity that comes with a life-changing illness, and learned how to adapt and thrive through passion and advocacy.

The Way Out by Alan Gordon

Psychotherapist Alan Gordon believes pain sufferers can break the cycle of chronic pain through the use of Pain Reprocessing Therapy (PRT), a form of mindfulness and cognitive behavioral therapy. PRT is based on the premise that the brain can generate pain even after an injury has healed, and that people can “unlearn” that pain by forming new brain connections.

Patient Z by Stefan Franzen

A comprehensive and well-researched book by chemistry professor Stefan Franzen, PhD, that looks at pain, addiction and the opioid crisis through the eyes of a patient. “Patient Z” can’t find good pain care because opioid medication has been criminalized and the field of pain management hijacked by regulators, anti-opioid activists and drug companies. There are millions of people like Patient Z who are caught in the middle of a growing pain crisis.

The Essential Guide to CBD by Reader’s Digest

You know CBD has gone mainstream when the Reader’s Digest publishes a book about it. This beginner’s guide to cannabidiol explains how CBD works and various ways to consume it, with anecdotes from people who use CBD to relieve pain and over two dozen medical conditions, from anxiety and migraines to acne and PTSD. The book is easy to understand and backed up with research — with good advice on where to buy reliable CBD products.

Recovery from Lyme Disease by Dr. Daniel Kinderlehrer

A book for both doctors and patients on a tick-borne disease that has infected over one million Americans, about 20% of them becoming chronically ill. Dr. Daniel Kinderlehrer became infected himself, and used his background in holistic and internal medicine to develop an integrative guide to diagnosing and treating Lyme disease with antibiotics, disulfiram, cannabis and other promising new therapies.

Exercised by Daniel Lieberman

Harvard professor Daniel Lieberman looks at the evolutionary history and myths about physical exercise. While important for overall health, Lieberman says exercise in small doses — simply getting up and moving — can be just as effective as running marathons or becoming a gym rat. Even just learning how to sit properly can exercise core muscles, help keep you fit, and significantly reduce back pain.

An Anatomy of Pain by Dr. Abdul-Ghaaliq Lalkhen

Anesthesiologist Abdul-Ghaaliq Lalkhen takes a deep dive into how the human mind and body experience pain and adapt to it. Lalkhen says pain is a complex mix of nerve endings, psychology, social attitudes and a person’s tolerance for discomfort. Each individual and circumstance is different. While acute pain from a broken bone or injury is easily accepted by society, pain that becomes chronic is often misunderstood and stigmatized.

Drug Use for Grown-Ups by Carl Hart

Columbia University psychology professor Carl Hart says all recreational drugs should be legally available for adult consumption. A regulated drug supply with uniform quality standards would be safer, create jobs, generate millions of dollars in tax revenue, and reduce accidental drug overdoses. Hart believes current drugs laws are unjust and their enforcement often racist.

Never Pay the First Bill by Marshall Allen

ProPublica reporter Marshall Allen wrote this book as a “guerilla guide” for patients who want to understand and contest inflated medical bills. One of his unconventional tips is to bypass your health insurance by purchasing drugs and medical devices on your own, without the markup seen in some insurer-negotiated rates. Allen also explains what to do and say in the hospital to avoid paying for procedures that are unnecessary.

These and other books and videos about living with chronic pain and illness can be found in PNN’s Suggested Reading section.

The High Price of Being Your Own Advocate

By Cynthia Toussaint, PNN Columnist

I’ve always encouraged women in pain to be strong advocates for their care. But after decades of pushbacks and harassment from the medical community for doing just that, I’m starting to question whether self-advocating does more harm than good.

The U.S. healthcare system is flat-out busted because it revolves around making money rather than making people well. The “standard of care” model of medicine is tried and true as profit generating, while it cloaks itself in the deceit of what’s in the patient’s best interest.

While individualized “patient-centered care” is often touted, and makes great buzzwords for marketing material, whenever I elect something out of the norm, my healthcare providers harass and bully me to return to their cookie-cutter model. When I don’t comply, my “care” gets ugly, causing me physical and emotional harm.  

I’ve bucked up against this thuggery for 39 years, the first 20 fighting an HMO. That was the trust breaker for me. After escaping that illness-provoking gulag, I felt certain that at last my care choices would be respected. I was wrong.

While a fresh pain management doctor initially helped, he soon pushed hard for interventions that I instinctively knew weren’t right for me. When I repeatedly said no to prescription fentanyl, ketamine infusions, two spinal cord stimulators and an intrathecal pump, this MD often called to bawl me out before slamming down the phone. For a time I put up with his tantrums because he was the first doctor who validated my Complex Regional Pain Syndrome (CRPS) diagnosis. But at last, my health couldn’t take his abuse and I cut this jackal loose.   

Cancer Diagnosis    

It gets worse. Twenty-two years ago, when I was first diagnosed with ductal carcinoma in situ (aka, “Stage Zero” breast cancer), my oncologist told me I had three months to live if I didn’t undergo surgery, chemotherapy and radiation.

Because my CRPS was a ginormous complication and to me the treatment didn’t match the diagnosis, I chose to “wait and watch.” That doctor was irate, even calling my home to press me into “life-preserving” treatment. Perhaps worse, he never celebrated the reality that my “cancer” ultimately came to nothing. Over the years, I’ve watched ductal carcinoma become a controversial diagnosis because of the over-treatment associated with it. Wow, I was almost a statistic.

In 2019, when I was diagnosed (in the other breast) with real cancer, stage 2 triple-negative, my first thought was, “God, please no, please, please, don’t make me wrangle with the western healthcare system again!”

In short order, I learned that cancer treatment is the mother of all standard of care, and in this do-or-die arena, you don’t ask questions. You say, “Thank you, sir. May I have another?” Problem is, that memo, now and forever, means nothing to me.

Naturally, I was threatened with impending death during the six months I carefully researched and considered treatment (my tumor actually shrunk during that time.) Then, after being a “super responder” to chemo, I turned down the standard-of-care follow up surgery. My tumor was gone, confirmed by imaging, and all studies showed that I had a better chance of survival without going under the knife.

I guess it won’t come as a surprise that every oncologist who crossed my path at that time said my choice was foolhardy, even madness, then chased that declaration with another death threat.

Boy oh boy, do I pay for sticking up for me. Since then, with every scan, they find a new “concern,” be it a shadow on an image or a thickening lymph node. One imaging doctor told me straight up that my cancer had returned and they expected me to jump back into their treatment assembly line.

I was this close to being spooked into that unnecessary surgery which, due to my CRPS, would likely have destroyed my life. Thank god a colleague questioned why they hadn’t done full scans to see if the cancer had spread first, stopping me in my tracks. Lo and behold, those scans were negative for any and all cancer. No matter. My doctors insisted on the operation, denying me a second opinion, the reason given, “Whether you have a malignancy or not, you have to do surgery.” I arranged for a second opinion at another hospital that confirmed I was cancer-free. Hallelujah!

During this hellish time, I paid the advocacy price in a new, heartbreaking way. I had a 15-year internist who I trusted with my life. In fact, she guided and supported me through all of my cancer treatment decisions. She alone respected the dangers of CRPS and recommended “de-escalation” from unnecessary treatment whenever possible.

The system didn’t like her interference though, and applied pressure. She dropped me as her patient when I needed her most. That was eight months ago, and I’m still working with a therapist, using guided imagery, hypnosis and EMDR therapy (eye movement desensitization and reprocessing), to unravel the trauma of that betrayal.

No Regrets

Despite it all, I move forward.      

Decades into CRPS and a year and a half out of cancer, I’m surprisingly feeling tip-top. That is, until it’s imaging time when the pummeling takes an exhausting toll. My pain and IBS flare, I hyperventilate, stop sleeping, my body gets tight and I have anxiety attacks. I don’t dread the cancer coming back (make no mistake, that fear is REALLY bad) as much as I dread the doctors new “concern” and the ongoing communiques that keep me in a place of anger, resentment and un-wellness.

Reflecting on my chosen role as a self-advocate, I still think the pros outweigh the cons for women in pain. We need to be in control of our treatment choices, whether they’re bucking the trend or going with the flow. And just as important, we need to be ready to walk away from an uncomfortable care situation.

Despite my self-advocacy nightmares, I have no regrets. I continue to make the best choices for me in this dysfunctional, profit-driven healthcare system. Still, I yearn for their support. I wish they’d care about and root for me. I wish they’d celebrate my good health. Mostly, I wish they’d stop harming me.

As I talk with other women angry about past cancer treatment they were coerced into, many who now deal with chronic pain as a result, I’m emboldened to continue speaking out about our fear-based model of over-treatment. My heart aches for them and for those who will come.

Fear and pressure should never drive our care decisions. The way I see it, the biggest mistake we women in pain can make is to sit on the sidelines of care and not do our job as advocates. If we hand our power over to the healthcare professionals and the systems that lord over them, we’re doomed.

The cost of compliance and victimhood is too damn high.                      

Cynthia Toussaint is the founder and spokesperson at For Grace, a non-profit dedicated to bettering the lives of women in pain. She has lived with CRPS and 19 co-morbidities for nearly four decades, and became a cancer survivor in 2020. Cynthia is the author of “Battle for Grace: A Memoir of Pain, Redemption and Impossible Love.”

Does U.S. Have Opioid Crisis or Overdose Crisis?

By Pat Anson, PNN Editor

A lot of people were surprised by an alarming report from the CDC last week, showing that a record 100,306 Americans died of a drug overdose in the 12-month period ending in April, 2021. That’s a 28.5% increase in a single year.

Among those who were caught off-guard was Andrew Kolodny, MD, an opioid researcher at Brandeis University and founder of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

“I was surprised by the latest tally from the CDC showing that for the first time ever, the number of Americans who fatally overdosed over the course of a year surpassed 100,000,” Kolodny wrote in an op/ed for The Conversation that’s been republished in several major newspapers.

“The soaring death toll has been fueled by a much more dangerous black market opioid supply. Illicitly synthesized fentanyl – a potent and inexpensive opioid that has driven the rise in overdoses since it emerged in 2014 – is increasingly replacing heroin. Fentanyl and fentanyl analogs were responsible for almost two-thirds of the overdose deaths.”

It’s refreshing to see Kolodny finally address the elephant in the room – illicit fentanyl – instead of always blaming prescription opioids for America’s addiction and overdose problem. But he continues to frame the drug crisis as an “opioid crisis” when repeated studies show that multiple substances are usually involved in overdoses, including non-opioid drugs like cocaine and methamphetamine.  

“It is especially tragic that these deaths are mainly occurring in people with a disease – opioid addiction – that is both preventable and treatable. Most heroin users want to avoid fentanyl. But increasingly, the heroin they seek is mixed with fentanyl or what they purchase is just fentanyl without any heroin in the mix,” Kolodny wrote.

“Opioid-addicted individuals seeking prescription opioids instead of heroin have also been affected, because counterfeit pills made with fentanyl have become more common.”

Here Kolodny sidesteps the fact that many pain patients are turning to street drugs because of government and law enforcement policies that restrict the prescribing of opioid medication – policies that Kolodny and PROP had a significant role in creating. They’re not addicts “seeking prescription opioids instead of heroin.” They’re patients seeking pain relief.

“Our misdirected efforts to solve the overdose epidemic have led to even more deaths. As long as we myopically focus on reducing prescription opioids for people in pain, the overdose epidemic will continue and worsen,” says Lynn Webster, MD, a pain management expert, Senior Fellow at the Center for U.S. Policy (CUSP) and Chief Medical Officer of PainScript.  

“Some of those who need opioids will be driven to the streets where they will find illicit and, potentially, lethal opioids. Some people may even choose to end their own lives. Your readers may have seen the recent article that described a suit against a physician for denying opioid treatment of a patient. The patient committed suicide as a result.” 

Webster says it is wrong to single out opioids – legal or illicit – for America’s escalating drug problem when the causes are complex and embedded in society. 

“We do have an overdose epidemic. Unfortunately, policymakers and the media have wrongly categorized it as an opioid epidemic rather than a drug overdose epidemic,” says Webster. “The roots of the overdose crisis are deep and seeded in despair from major shifts in socioeconomic conditions and lack of adequate and affordable healthcare. The Covid pandemic has made clear that social and mental health issues must be addressed if the overdose crisis is to be reversed. 

“The only solution to the overdose epidemic is to lower the demand. This will require a broad approach that involves addressing socioeconomic and mental health drivers of demand. More affordable and accessible treatment is important but will not solve the crisis.” 

Invested in Opioid Crisis 

Changing the narrative about the overdose crisis won’t be easy, since so many lawyers, politicians, healthcare companies and media outlets have invested in perpetuating the “opioid crisis.” Kolodny and other PROP board members have lucrative side hustles testifying as expert witnesses in opioid litigation cases for plaintiff law firms, which stand to make billions of dollars in contingency fees if their lawsuits are successful. 

One such case was decided by a federal jury in Cleveland today, which found that Walgreens, CVS and Walmart substantially contributed to addiction and overdoses in two Ohio counties by dispensing opioids in their pharmacies. The companies said they would appeal. 

“Plaintiffs' attorneys sued Walmart in search of deep pockets while ignoring the real causes of the opioid crisis-such as pill mill doctors, illegal drugs, and regulators asleep at the switch,” Walmart said in a statement. “And they wrongly claimed pharmacists must second-guess doctors in a way the law never intended and many federal and state health regulators say interferes with the doctor-patient relationship.”

Judges in Oklahoma and California recently ruled that opioid manufacturers are not “public nuisances” and can’t be held responsible for what people ultimately do with their drugs.  

Do You Get Adequate Pain Management?

By Victoria Reed, PNN Columnist

For the last few weeks, I’ve been suffering from persistent sinus and dental pain. Sinus pain is not new to me, as I have long-standing allergies which cause swelling in the nasal passages and chronic congestion that sometimes leads to an infection. The medications that I take for my rheumatoid arthritis increase the risk for all types of infections, as they suppress the immune system.  

After seeing a doctor, a sinus infection was diagnosed. Towards the end of a course of antibiotics, I had marked improvement with the sinus symptoms, but was still having considerable pain when chewing, which radiated to my right ear and jaw.  

Initially, I assumed that the pain was related to the sinus infection, but when that didn’t go away after finishing the antibiotics, I made an appointment to see my dentist. He did the usual poking and prodding around my gums and teeth, trying to find the source of the pain, and discovered two areas that could be the culprits. He did a flushing procedure of the gums to try to alleviate the pain. 

However, after the procedure was completed, I had such severe pain that all I could do was hold my head in my hands, while tears seeped out of my eyes. The pain was as bad as the pain I had felt while giving birth without an epidural! 

After more than a few minutes, my face and jaw continued to throb and the pain had not subsided. The dentist could see that I was in quite a bit of distress. He then asked me what the pain level was before I had come in. I replied that it had been a 5, but “now it’s a 10.”  

He sat down beside me and tried to explain what he believed the problem was. It was hard to concentrate, but I was able to understand what he was saying. He told me that he thought a tooth was cracked and that I needed to see an endodontist, a root canal specialist. He also prescribed another antibiotic.  

The dentist then stood up and patted me on the shoulder with compassion. Clearly, he was sorry for having amplified my pain. I appreciated his compassion, but I was ready to leave. At that point, all I wanted was to move on to whichever provider could relieve the awful pain.  

Then, to my surprise, I was offered opioid pain medication! 

This was something I absolutely did not expect. I had root canals for severe infections in the past, but no prescription opioids had been offered and I was sent home with instructions to take over-the-counter pain relievers. The days of getting opioid medication for severe dental pain were over, I assumed.  

However, after my initial shock, I politely declined the prescription. Why? Because I already receive a mild prescription opioid for my chronic pain conditions. Sure, I could have taken the prescription and not said a word about that, but I knew that I should honor the pain management contract I had signed with my doctor.  

While I believed that a stronger medication would have been helpful for my tooth pain, I did not want to risk being ejected from my pain management program. My contract (and nearly all pain management contracts) explicitly states that I am not allowed to receive any additional opioids from any other provider.  

I turned down the possibility of immediate relief of my dental pain so that I wouldn’t lose my regular prescription for chronic pain. I felt that I had no other choice. In addition, I didn’t want to be “red-flagged” by the pharmacy as a drug seeker, even though I did have a legitimate need for the new prescription.  

The pendulum has swung too far in the effort to control opioid overdoses and many people do not receive appropriate medications to treat their pain. I realize that I am one of the lucky ones to still get a prescription opioid, and I feel for those who aren’t as fortunate as me.  

Every patient should advocate for themselves, but if you are unable or afraid to, try having a family member or friend do it for you. Don’t settle for treatment that is less than optimal. If you are unhappy with your treatment or have intolerable side effects, discuss it with your doctor and ask for a different treatment plan. Doctors generally want to help, but some may feel that their hands are tied when it comes to prescribing opioids.  

Unfortunately, chronic pain patients must continue to jump through hoops in order to be treated ethically, fairly and adequately. Many are denied appropriate treatment due to prescribing limits and doctors’ fear of prosecution for prescribing opioids. I am hopeful that with the upcoming revision of the CDC opioid guideline, things will change for the better.  

Victoria Reed lives in Cleveland, Ohio. She suffers from endometriosis, fibromyalgia, degenerative disc disease and rheumatoid arthritis. 

Overdose Crisis Reaches Grim Milestone

By Roger Chriss, PNN Columnist

The CDC announced this week that the U.S. has seen over 100,000 drug overdose deaths in the 12-month period ending May, 2021. This record-high spike in overdoses is thought to be primarily a result of pandemic lockdowns and the continuing spread of illicit fentanyl.

National Institute on Drug Abuse director Nora Volkow, MD, told NPR that the overdoses “are driven both by fentanyl and also by methamphetamines" and predicted that the surge of fatalities would continue because of the spread of more dangerous street drugs.

Connecticut this week warned that fentanyl was found in marijuana and is the suspected cause of several near-fatal overdoses in the state. “This is the first lab-confirmed case of marijuana with fentanyl in Connecticut and possibly the first confirmed case in the United States,” said state public health Commissioner Manisha Juthani, MD.

When asked if there is anything giving hope about the future of the drug crisis, PROP co-founder Andrew Koldony, MD, told Axios, “Uh... not really.”

Public health is often depressing. It is also rarely simple. We are not going to arrest, restrict or treat our way out of the drug crisis. Although harm reduction and improved access to addiction services will help, they will not be sufficient to reverse current trends.

The U.S. does not even have good data on the street drug supply. RAND researcher Bryce Pardo, PhD, looking at better and more current data in Canada, sees designer street drugs becoming even more dangerous.

“There is a recent and alarming trend toward more harmful supply of drugs sold in illegal markets in Canada. Consumers in Ontario, Alberta, and British Columbia buying powder may be at greater risk for exposure to fentanyl mixed with novel benzodiazepines,” Pardo reported in JAMA Psychiatry. “There is a need to improve monitoring and surveillance of drug consumption in the US as markets continue to trend toward more harmful drug mixtures.”

The U.S. also doesn’t have good data on drug deaths. Even the term “overdose” is problematic now. Deaths that are “opioid involved” in toxicological terms are resulting from inadvertent exposure via tainted cocaine and methamphetamine. And although fentanyl and other opioids are still involved in the majority of deaths, there are now more psychostimulant-involved deaths than there were two decades ago.

The U.S. also lacks good data on the people who died, in particular their drug use history, general health status, and other factors thought to affect drug risks and outcomes. It is easy to speculate that the stress and isolation of the pandemic exacerbated existing risks, but it is important to note that suicides did not rise in 2020 when they might have been expected to.

There is no easy policy fix here. Restricting prescription opioids and legalizing cannabis didn’t work. Ideology will not help. Legalizing drugs is a meaningless slogan since neither “drugs” nor “legalization” is well-defined. The same with old narratives and origin stories about the crisis, which may help explain what happened but contribute little about what to do next.

Safe supply is an appealing but problematic notion. There is no obvious way to test illicit substances in human trials. Illicit labs are unlikely to hold back their products any more than illicit cannabis suppliers are going to obey the law. Street drug test kits might help, if only we knew enough about the drugs and their users.

Treatment is similarly challenging. As Kolodny told Axios, “If we really want to see deaths come down in the short run, someone who's opioid addicted has to be able to access treatment more easily than they can buy a bag of heroin or fentanyl.” Though this is an admirable goal, there is no practical way to do it.

And all of this assumes that street users are opioid-addicted. More and more are not, as the increasing levels of death and harm from psychostimulants shows. Further, an increasing number of deaths are “polydrug” deaths involving two or more substances, which makes addressing risks all the more complicated.

But despair is not the appropriate response. The U.S. was facing rapidly rising rates of tobacco-related illness and death for much of the 20th century. But a combination of public health measures has cut the mortality rate from smoking in half since 1990. These measures include stricter laws and regulations, increased costs, and in an unexpected irony, stigmatization of smoking.

Many of the proposed solutions to the drug crisis have been based more on intuition than data. At this point we simply do not know which public health measures are working or how to improve them. What little data we have is often imprecise and years old, and as the crisis accelerates, the importance of granular and timely data grows. Moreover, the measures to date have often been applied piecemeal for short periods, so their real efficacy remains to be determined.

The tragedy of drug deaths cannot be understated, and the potential for far more drug deaths cannot be underestimated. But if the U.S. can improve its understanding of drugs and its response to risks and harms, we needn’t see so many more deaths moving forward.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research. 

Unusual Head-to-Head Migraine Study Pits Emgality vs. Nurtec

By Pat Anson, PNN Editor

Competition has grown intense between pharmaceutical companies in the $2 billion U.S. migraine market.

You’ve probably seen their TV commercials. Eli Lilly hired Olympic athletes to pitch Emgality, an injectable migraine preventative, while reality star Khloé Kardashian is appearing in commercials for Nurtec, an oral medication made by Biohaven Pharamceuticals

Lilly is now taking the competition a step further, with an unusual head-to-head clinical study – rare in the pharmaceutical industry – that pits Emgality against Nurtec. The company is enrolling 700 adults with episodic migraine in a randomized, double-blind, placebo-controlled trial. The so-called CHALLENGE-MIG study will directly compare the efficacy and safety of the two drugs.

“Lilly’s CHALLENGE-MIG study will help us understand how different types of preventive medications may help people achieve the goals that matter most to them. It’s exciting that insights generated in this first-of-its-kind head-to-head trial will be able to spark treatment plan discussions between people with migraine and their health care providers,” Shivang Joshi, MD, a trial investigator at Dent Neurologic Institute, said in a Lilly press release.

Emgality and Nurtec both inhibit calcitonin gene-related peptides (CGRP), a protein that causes migraine pain, but their delivery systems are very different. Emgality is injected once a month, while Nurtec is taken in a pill every other day.

Emgality was one of the first CGRP inhibitors to be approved by the FDA in 2018, while Nurtec is a relative newcomer, first approved in 2020. Nurtec’s label was recently expanded to include both migraine prevention and treatment.

The primary goal of the Lilly study is to see which drug gives patients a greater reduction in monthly headache days, with a secondary goal of measuring quality of life improvements.

“We believe patients should expect more and get more from medications that can help prevent migraine. Therefore, we look forward to sharing the findings from our Emgality versus Nurtec ODT head-to-head trial,” said Anne White, senior vice president of Eli Lilly and president of Lilly Neuroscience.

Biohaven’s CEO welcomes the study and sees it as an affirmation of Nurtec’s growing share of the market. Since it was introduced last year, Nurtec has generated about $200 million in revenue for Biohaven, with over 750,000 prescriptions filled. 

"This new head-to-head trial affirms that Nurtec ODT is perceived as the new standard of care.  The dual-therapy action of Nurtec ODT is unique and provides clear advantages to both treat and prevent migraine attacks.  Since the launch of oral acute CGRP agents, the performance of injectable CGRP (inhibitors) is now negligible to flat,” Vlad Coric, MD, CEO of Biohaven Pharmaceuticals, said in a statement to PNN. 

“Regardless of this Emgality study outcome, the Nurtec ODT value proposition will not be matched. And Nurtec ODT will have an impressive and entrenched market penetration by the completion of the proposed head-to-head study.  We continue to hear from patients, who want oral over needle-based therapies.” 

Regardless of whether it’s a pill or injection, both drugs are expensive. A supply of eight Nurtec tablets costs about $941, depending on insurance coverage. The listed price for Emgality is $627 for a single injection or about $7,524 annually.

If you’d like to know more about the study or possibly enroll in it, call the Lilly Answers Center at 1-800-545-5979.

Exercise Reduces Pain by Increasing Beneficial Bacteria

By Pat Anson, PNN Editor

Regular exercise can benefit people in many different ways, helping us lose weight, reduce the risk of heart disease, and boosting overall health.  

But researchers at the University of Nottingham have found that exercise has an unexpected benefit for people with arthritis. Regular exercise increases levels of beneficial bacteria in their digestive tracts, which reduces pain and inflammation by increasing levels of endocannabinoids – cannabis-like substances naturally produced by the body.

The study, published in the journal Gut Microbes, is believed to be the first to find a potential link between endocannabinoids, exercise and gut microbes.

"Our study clearly shows that exercise increases the body's own cannabis-type substances. Which can have a positive impact on many conditions,” says lead author Amrita Vijay, a Research Fellow at Nottingham’s School of Medicine. "As interest in cannabidiol oil and other supplements increases, it is important to know that simple lifestyle interventions like exercise can modulate endocannabinoids."

Vijay and her colleagues enrolled 78 people in their study. Half of the participants did 15 minutes of muscle strengthening exercises every day for six weeks, and the rest did nothing. Blood and fecal samples were collected from both groups.

At the end of the study, participants who exercised not only had lower pain levels, they also had significantly more Bifidobacteria and Coprococcus 3 -- bacteria that produce anti-inflammatory substances and lower levels of cytokines, which regulate inflammation.

These gut bacteria were particularly adept at raising levels of short chain fatty acids (SCFAs), which increase levels of endocannabinoids. About a third of the anti-inflammatory effects of the gut microbes was due to their ability to raise endocannabinoid levels.

Importantly, the exercise group also had lower levels of Collinsella – a bacteria known to increase inflammation that is strongly associated with processed food and diets low in vegetables.    

“In this study we show that circulating levels of ECs (endocannabinoids) are consistently associated with higher levels of SCFAs, with higher microbiome diversity and with lower levels of the pro-inflammatory genus Collinsella. We also show statistically that the anti-inflammatory effects of SCFAs are up to one third mediated by the EC system,” researchers concluded.

Previous studies have also found an association between gut bacteria and painful conditions. A 2019 study at McGill University found that women with fibromyalgia had 19 different species of bacteria that were present in either greater or lesser quantities than a healthy control group.

Bacteria associated with irritable bowel syndrome, chronic fatigue syndrome and interstitial cystitis were also found to be abundant in the fibromyalgia patients, but not in the control group.    

Having a healthy diet can also affect pain levels for migraine, neuropathy and other types of chronic pain. A recent study funded by the National Institutes of Health found that migraine sufferers who ate more fatty fish and reduced their consumption of polyunsaturated vegetable oils — frequently found in processed foods — had fewer headaches.