Vaccines Help Some Covid Long Haulers

By Will Stone, Kaiser Health News

An estimated 10% to 30% of people who get covid-19 suffer from lingering symptoms of the disease, or what’s known as “long covid.”

Judy Dodd, who lives in New York City, is one of them. She spent nearly a year plagued by headaches, shortness of breath, extreme fatigue and problems with her sense of smell, among other symptoms.

Dodd worried that this “slog through life” was going to be her new normal. But everything changed after she got her covid vaccine.

“I was like a new person. It was the craziest thing ever,” said Dodd, referring to how many of her health problems subsided significantly after her second shot.

As the U.S. pushes to get people vaccinated, a curious benefit is emerging for those with this post-illness syndrome: Their symptoms are easing and, in some cases, fully resolving after vaccination.

It’s the latest clue in the immunological puzzle of long covid, a still poorly understood condition that leaves some who get infected with wide-ranging symptoms months after the initial illness.

The notion that a vaccine aimed at preventing the disease may also treat it has sparked optimism among patients, and scientists who study the post-illness syndrome are taking a close look at these stories.

“I didn’t expect the vaccine to make people feel better,” said Akiko Iwasaki, an immunologist at the Yale School of Medicine who’s researching long covid.

“More and more, I started hearing from people with long covid having their symptoms reduced or completely recovering, and that’s when I started to get excited because this might be a potential cure for some people.”

While promising, it’s still too early to know just how many people with long covid feel better as a result of being vaccinated and whether that amounts to a statistically meaningful difference.

In the meantime, Iwasaki and other researchers are beginning to incorporate this question into ongoing studies of long haulers by monitoring their symptoms pre- and post-vaccination and collecting blood samples to study their immune response.

There are several leading theories for why vaccines could alleviate the symptoms of long covid: It’s possible the vaccines clear up leftover virus or fragments, interrupt a damaging autoimmune response or in some other way “reset” the immune system.

“It’s all biologically plausible and, importantly, should be easy to test,” said Dr. Steven Deeks of the University of California-San Francisco, who is also studying the long-term impacts of the coronavirus on patients.

Patient Stories Offer Hope

Before getting the vaccine, Dodd, who’s in her early 50s, said she felt as if she had aged 20 years. She had trouble returning to work, and even simple tasks left her with a crushing headache and exhaustion.

“I’d climb the subway stairs and I’d have to stop at the top, take my mask off just to get air,” Dodd said.

After she got her first dose of the Pfizer vaccine in January, many of Dodd’s symptoms flared up, so much so that she almost didn’t get her second dose.

But she did — and a few days later, she noticed her energy was back, breathing was easier and soon even her problems with smell were resolving.

“It was like the sky had opened up. The sun was out,” she said. “It’s the closest I’ve felt to pre-covid.”

In the absence of large studies, researchers are culling what information they can from patient stories, informal surveys and clinicians’ experiences. For instance, about 40% of the 577 long-covid patients contacted by the group Survivor Corps said they felt better after getting vaccinated.

Among the patients of Dr. Daniel Griffin at Columbia University Medical Center in New York, “brain fog” and gastrointestinal problems are two of the most common symptoms that seem to resolve post-vaccination.

Griffin, who is running a long-term study of post-covid illness, initially estimated that about 30% to 40% of his patients felt better. Now, he believes the number may be higher, as more patients receive their second dose and see further improvements.

“We’ve been sort of chipping away at this [long covid] by treating each symptom,” he said. “If it’s really true that at least 40% of people have significant recovery with a therapeutic vaccination, then, to date, this is the most effective intervention we have for long covid.”

A small U.K. study, not yet peer-reviewed, found about 23% of long-covid patients had an “increase in symptom resolution” post-vaccination, compared with about 15% of those who were unvaccinated.

But not all clinicians are seeing the same level of improvement.

Clinicians at post-covid clinics at the University of Washington in Seattle, Oregon Health & Science University in Portland, National Jewish Health in Denver and the University of Pittsburgh Medical Center say only a small number of patients — or none at all — have reported feeling better after vaccination.

“I’ve heard anecdotes of people feeling worse, and you can scientifically come up with an explanation for it going in either direction,” said UCSF’s Deeks.

Why Are Patients Feeling Better?

There are several theories for why vaccines could help some patients — each relying on different physiological understandings of long covid, which manifests in a variety of ways.

“The clear story is that long covid isn’t just one issue,” said Dr. Eric Topol, director of the Scripps Research Translational Institute, which is also studying long covid and the possible therapeutic effects of vaccination.

Some people have fast resting heart rates and can’t tolerate exercise. Others suffer primarily from cognitive problems, or some combination of symptoms like exhaustion, trouble sleeping and issues with smell and taste, he said.

As a result, it’s likely that different therapies will work better for some versions of long covid than others, said Deeks.

One theory is that people who are infected never fully clear the coronavirus, and a viral “reservoir,” or fragments of the virus, persist in parts of the body and cause inflammation and long-term symptoms, said Iwasaki, the Yale immunologist.

According to that explanation, the vaccine might induce an immune response that gives the body extra firepower to beat back the residual infection.

“That would actually be the most straightforward way of getting rid of the disease, because you’re getting rid of the source of inflammation,” Iwasaki said.

Griffin at Columbia Medical Center said this “viral persistence” idea is supported by what he’s seeing in his patients and hearing from other researchers and clinicians. He said patients seem to be improving after receiving any of the covid vaccines, generally about “two weeks later, when it looks like they’re having what would be an effective, protective response.”

Another possible reason that some patients improve comes from the understanding of long covid as an autoimmune condition, in which the body’s immune cells end up damaging its own tissues.

A vaccine could hypothetically kick into gear the “innate immune system” and “dampen the symptoms,” but only temporarily, said Iwasaki, who has studied the role of harmful proteins, called autoantibodies, in covid.

This self-destructive immune response happens in a subset of covid patients while they are ill, and the autoantibodies produced can circulate for months later. But it’s not yet clear how that may contribute to long covid, said John Wherry, director of the Institute for Immunology at the University of Pennsylvania.

Another theory is that the infection has “miswired” the immune system in some other way and caused chronic inflammation, perhaps like chronic fatigue syndrome, Wherry said. In that scenario, the vaccination might somehow “reset” the immune system.

With more than 77 million people fully vaccinated in the U.S., teasing apart how many of those with long covid would have improved even without any intervention is difficult.

“Right now, we have anecdotes; we’d love it to be true. Let’s wait for some real data,” said Wherry.

This story is part of a partnership that includes NPR and Kaiser Health News (KHN), a national newsroom that produces in-depth journalism about health issues.

Pilot Study Shows Neuromodulation Effective for Postoperative Pain

By Pat Anson, PNN Editor

In recent years, many U.S. hospitals have adopted policies that reduce or eliminate the use of opioids after surgery. For some, that means giving their patients Tylenol or Lyrica for postoperative pain. For others, it means trying neuromodulation — a non-pharmacological therapy that new research shows may have some potential.

In a placebo-controlled pilot study led by researchers at University of California San Diego, patients who received percutaneous peripheral nerve stimulation (PNS) had significant reductions in their pain levels after outpatient joint surgery.

Percutaneous PNS is a form of neuromodulation that involves the placement of a tiny wire or “lead” alongside a peripheral nerve. The implanted lead is then connected to a small external pulse generator that sends a mild electric current to the nerve, interrupting pain signals. PNS has been used for years to treat chronic pain, but this was the first clinical trial to assess its use for postoperative acute pain.    

In the pilot study, 65 adult patients scheduled for operations on their shoulders, knees or ankles had leads placed before surgery in the affected joint. After surgery, half of the patients were given neuromodulation, while the other half received a "sham" treatment with a pulse generator that appeared active but did not deliver any electric current.

Patients in both groups received opioids as needed for their postoperative pain, and after one week their pain scores and opioid use were compared.

Researchers reported in the journal Anesthesiology that the results were “much greater than we had anticipated.” Pain scores were over 50 percent lower in patients who received neuromodulation. The mean pain score (on a zero to ten scale) was 1.1 in patients receiving PNS treatment, compared to 3.1 in the sham group.

Nerve stimulation was also associated with an 80 percent reduction in opioid consumption. The median opioid dose (oral morphine equivalent) in the first week after surgery was 5 milligrams in the active treatment group, compared to 48 milligrams in the sham group.

“This multicenter, randomized, double-masked, sham- controlled pilot study provides evidence that ultra-sound-guided percutaneous peripheral nerve stimulation concurrently improves analgesia and decreases opioid requirements to a statistically significant and clinically meaningful degree for at least a week after moderately to severely painful ambulatory orthopedic surgery,” wrote lead author Brian Ilfeld, MD, a professor of anesthesiology at UC San Diego.

Ilfeld and his colleagues say the pain-relieving benefits of neuromodulation continued after the leads were removed 14 days after surgery, but they appeared to wear off after one month. They plan on conducting a larger clinical trial with 250 surgery patients and to follow them for a year to see if there are any long-term benefits from neuromodulation.

Contrary to popular belief, opioid addiction is rare after surgery. A large 2016 study found only 0.4% of older adults were still taking opioids a year after major elective surgery. Another large study in 2018 found only 0.2% of patients who took opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or had a non-fatal overdose.

Nevertheless, the now defunct American Pain Society (APS) released guidelines in 2016 that encourage physicians to use non-opioid medication such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin (Neurotin) and pregabalin (Lyrica) for post-operative pain. The APS also recommended non-pharmacological therapies such as cognitive behavioral therapy and transcutaneous elective nerve stimulation (TENS) as adjunct treatments.

The lead author of the APS guideline was Roger Chou, MD, who also co-authored the 2016 CDC opioid guideline.

Urine Tests Show Medical Cannabis Often Mislabeled

By Pat Anson, PNN Editor

Pick up almost any canned or packaged food in a grocery store and you’ll see a lengthy list of its ingredients, right down to the amount of sodium, fat, vitamins and calories in each serving.

That kind of attention to detail – and truth in advertising -- continues to elude the cannabis industry, according to a new study that found the amount of THC and CBD listed on many medical cannabis products to be wildly inaccurate.

Researchers at Massachusetts General Hospital didn’t test the products themselves, but instead analyzed urine samples from nearly 100 patients who frequently used medical cannabis to treat their pain, anxiety, depression or insomnia. Vaping was the most common form of administration, but patients also smoked or ingested cannabis products purchased at Boston-area dispensaries.   

Laboratory testing showed no CBD metabolites in about a third of the urine samples from patients who said they used cannabis products that were mostly CBD or had equal parts THC and CBD. THC was detected in nearly 80% of those samples, including ones from patients who thought they were only ingesting CBD.

The distinction is important because THC (tetrahydrocannabinol) is the psychoactive ingredient in cannabis that can make users high, while CBD (cannabidiol) is the chemical compound believed to have health benefits.

"People are buying products they think are THC-free but in fact contain a significant amount of THC," says lead author Jodi Gilman, PhD, an investigator in the Center for Addiction Medicine in Massachusetts General’s Department of Psychiatry. "One patient reported that she took a product she thought only contained CBD, and then when driving home that day she felt intoxicated, disoriented and very scared."

About 20% of patients who used a vaporizer had no detectable levels of either THC or CBD in their urine. Researchers think that’s because some vaping devices may not heat cannabis products sufficiently for patients to inhale the active ingredients. THC was more likely to be found in patients who smoked cannabis or ingested it orally.

"A lot of questions about the content of the products and their effects remain," says Gilman. "Patients need more information about what's in these products and what effects they can expect."

The study findings, published in JAMA Network Open, are the latest to show that the actual ingredients in cannabis products vary considerably from their labels. Although 36 states and Washington DC have legalized medical cannabis, there is little consistency in labeling, regulating or testing medical cannabis, as there is for food, supplements and pharmaceutical drugs.

A 2015 study of cannabis edibles sold in California and Washington found that only 17% were labeled accurately. Over half had significantly less CBD than labeled and some had negligible amounts of THC.   

A recent study conducted by the Food and Drug Administration of 147 hemp and cannabis products found that less than half contained CBD within 20% of their label declarations.   

Do You Have Central Sensitization or Intractable Pain?

By Forest Tennant, PNN Columnist

Chronic pain patients may now be told by their doctor, nurse practitioner or pharmacist that they have “central sensitization” (CS). This vague, non-descriptive term is unfortunate in many ways. Nevertheless, it appears to be here to stay. 

Since Intractable Pain Syndrome (IPS) is a far more serious condition that requires an aggressive, multi-component treatment approach, it is essential to know the difference between IPS and CS. 

Going forward, we believe that it will be increasingly difficult to obtain some medications unless you have IPS. Therefore, it is of vital importance to not only know if you have IPS, but you must be able to clearly explain it to your physicians, family and insurance carrier. If you have simple chronic pain or CS, you could be quite limited in obtaining many prescription medications. 

Definition of Central Sensitization: Amplification or heightened pain above what would normally be expected from tissue damage or injury. 

CS occurs when brain tissue starts to alter due to excess electric currents that originate in damaged or injured tissue. Brain tissue alteration is referred to as neuroplasticity. CS can often be recognized if pain advances, because it begins to cause insomnia and requires daily, rather than “as-needed” medication. 

CS is the forerunner or precursor of IPS. Almost all persons with IPS have had or currently have CS. There is a movement among medical practitioners to recognize CS and treat it with drugs like duloxetine (Cymbalta) or pregabalin (Lyrica) to prevent it from advancing to IPS. 

Definition of Intractable Pain Syndrome: Constant, incurable pain with cardiovascular, endocrine and autoimmune complications.

Only some medical conditions cause IPS. The most common are arachnoiditis, Ehlers-Danlos syndrome, brain injury and Reflex Sympathetic Dystrophy (RSD or CRPS). 

Levels of estradiol and testosterone often go down with IPS, causing symptoms which include amenorrhea in women (missed menstrual periods), impotence in men, fatigue, loss of sex drive, osteoporosis and loss of teeth.

Your autoimmune system will also be affected by IPS, causing elevation of inflammatory markers, cytokines, proteins, and white blood cells.

This could result in symptoms of fibromyalgia, thyroiditis, carpel tunnel syndrome, TMJ, mast cell activation, and migratory joint pains.  

Pain from IPS will cause elevations of pulse and blood pressure. Cortisone and insulin levels will also go up, causing elevations in glucose and cholesterol.

“Going forward, we believe that it will be increasingly difficult to obtain some medications unless you have IPS... If you have simple chronic pain or CS, you could be quite limited in obtaining many prescription medications.”

— Forest Tennant

It is up to the pain patient with IPS to educate all concerned parties that their CS has turned into IPS and that it is a serious syndrome with cardiovascular, endocrine, and auto-immune complications. 

Each person with constant pain needs to catalogue the above manifestations and make a record to give to your medical practitioners and pharmacist. If you haven’t had blood tests for hormone and autoimmune dysfunction, you must request these be done. Please review our website and obtain materials on IPS for your medical practitioners and pharmacist. 

Forest Tennant 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.   

Few Patients on Long-Term Opioids Engage in Risky Behavior

By Pat Anson, PNN Editor

Only a small percentage of pain patients on long-term opioid therapy ask for higher doses, renew their prescriptions early or divert their medication to another person, according to a new study that challenges many common assumptions about prescription opioids.

For five years, Australian researchers followed over 1,500 patients taking opioid pain medication, with annual interviews asking them about their opioid use and behavior. The study is believed to be the first of its kind to follow patients on opioid therapy for such a long period.   

Most of the patients suffered from chronic back, neck or arthritis pain, and were taking opioids for at least 6 weeks at the start of the study, including about 15% who were taking high doses exceeding 200 MME (morphine milligram equivalent) per day. The CDC opioid guideline recommends that daily doses not exceed 90 MME.  

Researchers found that “problematic opioid use” was infrequent and steadily declined over time, with less than 10% of patients asking for higher doses or for a prescription to be renewed early. Less than 5% of patients tampered with their medications or diverted them to another person.     

“Contrary to the predominant thinking in pain management, the findings of this study suggest considerable fluidity in opioid use over time among many patients with CNCP (chronic non-cancer pain) who use opioids,” wrote lead author Louisa Degenhardt, PhD, Deputy Director of the National Drug and Alcohol Research Centre at University of New South Wales.

By the end of the study, patients were more likely to have stopped taking opioids (20%) than they were to be diagnosed with opioid dependence (8%), suggesting that long-term opioid use does not always lead to dependence or addiction. Even when they were diagnosed as opioid dependent, most patients did not meet the criteria for dependence the following year, suggesting the original diagnosis was faulty.

JAMA Network Open

Researchers noted there was “substantial variation” in how patients answered questions from year to year about their opioid use and behavior. Most who reported risky behavior did so in only one of the annual interviews.  

“This finding challenges a common view that the risk of opioid-related behaviors is static and that risk assessment at the start of opioid treatment can predict which patients will develop opioid use disorder,” researchers concluded in JAMA Network Open. “By contrast, individuals who engage in opioid-related behaviors change over time, which also suggests that opioid behaviors of concern need not persist.”

“This study shows what most clinicians treating CNCP with opioids already know, which is that most individuals do fine with chronic opioid therapy. It is only a few people who develop a problem, and that can’t be easily predicted based on a person's early behaviors associated with opioids prescribed for pain,” said Dr. Lynn Webster, a PNN columnist and past president of the American Academy of Pain Medicine.

“It refutes the argument that patients on chronic opioid therapy inevitably will abuse, become addicted, or never cease using opioids once started.” 

Webster noted that most people in the study were stable and few demonstrated any abuse or harm from opioids, including those on high doses who were less likely to ask for more medication.

“I think the overriding message of this study is that the one-size-fits all approach to using opioids for CNCP is flawed. The idea that everyone should be at a low level doesn't address individual needs,” Webster said.

No Relationship Between Rx Opioids and Injury Deaths

Another new study that challenges conventional thinking about prescription opioids found that high doses are not associated with higher rates of trauma-related death.

Researchers at Case Western Reserve University looked at mortality rates in all 50 states from 2006 to 2017, comparing them to the amount of opioids prescribed during the same period.

The researchers believed they would find a relationship between opioids and higher death rates. Their theory was that people on opioids were more likely to be impaired, which would lead to more car crashes, accidents, drownings, suicides and other types of trauma death.

But in findings reported in the journal Injury, there was no association between the two.

“In every state examined, there was no consistent relationship between the amount of prescription opioids delivered and total injury-related mortality or any subgroups, suggesting that there is not a direct association between prescription opioids and injury-related mortality,” wrote lead author Esther Tseng, MD, a trauma surgeon and professor at CWRU.

It's important to note that Tseng and her colleagues did not look at fatal overdoses caused by prescription opioids. Previous research by the CDC has found that deaths linked to opioid pain medication have been relatively flat for nearly a decade. The vast majority of overdoses involve illicit fentanyl and other street drugs.    

Harvard Study Finds Cannabis Effective for Chronic Pain

By Pat Anson, PNN Editor

Long-term use of medical cannabis may be an effective treatment for chronic pain, according to a small study by researchers at Harvard Medical School and McLean Hospital in Boston.

Thirty-seven patients suffering from arthritis, joint pain, neuropathy and other chronic pain conditions were evaluated over a six-month period while ingesting cannabis products through smoking, vaporizing, edibles, oils and other methods. All of the patients were cannabis “naive” — meaning they had never used cannabis before or had abstained from use for at least a year prior to the study.

After six months of daily treatment with cannabis, patients reported significant improvements in their pain, sleep, mood, anxiety and quality of life. Their use of opioid pain medication declined by an average of 13% and 23% after 3 and 6 months of treatment, respectively, although not to a degree that was considered significant.

A control group of 9 pain patients that did not use cannabis did not have a similar pattern of improvement in pain or other symptoms. 

“This naturalistic study of medical cannabis (MC) patients with chronic pain provides preliminary evidence that ‘real world’ MC treatment may be a viable alternative or adjunctive treatment for a least some individuals with chronic pain,” wrote lead author Staci Gruber, PhD, Associate Professor of Psychiatry at Harvard Medical School. 

“As results also revealed that individual cannabinoids appear to exert unique effects on pain and comorbid symptoms, more research is needed to potentially optimize cannabinoid-based treatments for pain.”

Gruber and her colleagues say increased exposure to tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis, appeared to be closely related to improvements in pain, while increased CBD exposure was related to improvements in mood, but not pain. Many patients reduced their use of THC as the study progressed.

“Interestingly, we have found that many patients aim to achieve symptom alleviation without experiencing the intoxicating effects of THC. Therefore, it is likely that patients are able to achieve adequate pain relief using lower doses of THC over time than initially utilized,” said Gruber, who heads the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital.

Researchers say additional studies are needed to explore how THC and CBD modulate pain and other symptoms. Their findings are published in the journal Experimental and Clinical Psychopharmacology.  

While the findings are intriguing, the small number of patients involved in this and most other cannabis studies makes it hard to draw firm conclusions.  

Last month two professional pain societies – the International Association for the Study of Pain (IASP) and the Australian and New Zealand College of Anaesthetists -- released statements saying they could not endorse the use of cannabis to treat pain because there are no large, high-quality and unbiased clinical trials of cannabis as an analgesic.

Genetics May Explain Why Women Are More Likely to Have Chronic Pain

By Pat Anson, PNN Editor

It’s no secret that women are far more likely than men to experience fibromyalgia, migraine, osteoarthritis and other chronic pain conditions. Why that is has been linked to everything from gender bias in healthcare to childhood trauma to women “catastrophizing” about their pain.  

A new study published by UK researchers in PLOS Genetics suggests that part of the reason is genetic differences between men and women.

In the largest genetic study of its kind, researchers at the University of Glasgow looked for genetic variants associated with chronic pain in over 209,000 women and 178,000 men who donated their medical and genetic data to the UK Biobank.

The researchers also investigated whether the activity of those genes was turned up or down in tissues commonly involved with chronic pain.

They found that 37 genes in men and 30 genes in women were active in the dorsal root ganglion, a cluster of nerves in the spinal cord that transmit pain signals from the body to the brain.

The findings support previous work by the same research team, which found that chronic pain originates to a large extent in the brain, and to a lesser degree in parts of the body where people “feel” pain. The study also suggests genetic differences between men and women may affect the immune system and how the two sexes respond to medication.

“Overall, our findings indicate the existence of potential sex differences in chronic pain at multiple levels… and the results support theories of strong nervous system and immune involvement in chronic pain in both sexes,” wrote lead author Keira Johnston of the University of Glasgow. "Our study highlights the importance of considering sex as a biological variable and showed subtle but interesting sex differences in the genetics of chronic pain."

Gender Bias

While genetic differences may partially explain why women are more likely to feel pain than men, gender biases may explain why they are treated differently, according to another study recently published in the Journal of Pain.

Researchers at the University of Miami found that when volunteers observed male and female patients expressing the same amount of pain, they had a tendency to view female patients' pain as less intense and more likely to benefit from psychotherapy.

The study consisted of two experiments in which adult volunteers were asked to view videos of men and women who suffered from shoulder pain. The videos came from a database of real patients experiencing different degrees of pain, and included their self-reported pain levels when moving their shoulders in a series of exercises.

The volunteer observers were asked to gauge the amount of pain they thought the patients in the videos experienced. They were also asked how much pain medication and psychotherapy they would prescribe to each patient, and which of the treatments they thought would be more effective.

The study found that female patients were perceived to be in less pain than the male patients — even when they reported and exhibited the same pain levels. Researchers believe those perceptions were partially explained by gender-based stereotypes.

"If the stereotype is to think women are more expressive than men, perhaps 'overly' expressive, then the tendency will be to discount women's pain behaviors," said co-author Elizabeth Losin, PhD, assistant professor of psychology at the University of Miami.

"The flip side of this stereotype is that men are perceived to be stoic, so when a man makes an intense pain facial expression, you think, 'Oh my, he must be dying!' The result of this gender stereotype about pain expression is that each unit of increased pain expression from a man is thought to represent a higher increase in his pain experience than that same increase in pain expression by a woman."

The volunteer observers were also more likely to choose psychotherapy as a treatment than pain medication for the female patients.

Interestingly, the gender of the observers did not influence pain estimation. Both men and women interpreted women's pain to be less intense.

"I think one critical piece of information that could be conveyed in medical curricula is that people, even those with medical training in other studies, have been found to have consistent demographic biases in how they assess the pain of male and female patients and that these biases impact treatment decisions," said Losin.

"Critically, our results demonstrate that these gender biases are not necessarily accurate. Women are not necessarily more expressive than men, and thus their pain expression should not be discounted."

UK Guidelines Recommend Exercise and Antidepressants for Chronic Pain

By Pat Anson, PNN Editor

Doctors in the United Kingdom are being advised not to prescribe any type of painkiller to patients suffering from fibromyalgia, chronic headache, Complex Regional Pain Syndrome (CRPS), chronic musculoskeletal pain and other types of “primary chronic pain” for which there is no known cause.   

Those conditions should be treated with exercise, cognitive behavioral therapy (CBT), acupuncture and antidepressants, according to new guidelines released by the UK’s National Institute for Health and Care Excellence (NICE). The NICE guideline is far more strict on the use of analgesics than current treatment guidelines in the U.S. and Canada.

The recommendation against using painkillers goes beyond just opioids, and includes many widely used pain relievers such as paracetamol (acetaminophen), non-steroidal anti-inflammatory drugs (NSAIDs), gabapentinoids and corticosteroids, as well as benzodiazepines such as Valium and Xanax.

“There is little or no evidence that they make any difference to people’s quality of life, pain or psychological distress, but they can cause harm, including possible addiction,” NICE said in a statement.

The guideline says antidepressants such as duloxetine (Cymbalta) and fluoxetine (Prozac) “can be considered” for adults 18 and over with chronic primary pain, even when there is no diagnosis of depression. NICE said antidepressants may help with quality of life, pain, sleep and psychological distress.

“This guideline is very clear in highlighting that, based on the evidence, for most people it’s unlikely that any drug treatments for chronic primary pain, other than antidepressants, provide an adequate balance between any benefits they might provide and the risks associated with them,” Dr. Paul Chrisp, director of NICE’s Centre for Guidelines, said in a statement.

“People who are taking medicines to treat their chronic primary pain which aren’t recommended in the guideline should ask their doctor to review their prescribing as part of shared decision making. This could involve agreeing a plan to carry on taking their medicines if they provide benefit at a safe dose and few harms, or support for them to reduce and stop the medicine if possible.”

The NICE guideline sticks to more traditional recommendations for treating “chronic secondary pain” for which there is a known underlying cause, such as osteoarthritis, rheumatoid arthritis, ulcerative colitis and endometriosis. Pain management for palliative care is not covered in the guideline.

‘Patently Ridiculous’

Although a draft version of the NICE guideline was released last August, pain sufferers were startled by some of the final recommendations, especially those for acupuncture, CBT and exercise.

“The idea that a run around the block will zap the torment of people in chronic pain is patently ridiculous. It doesn’t do a damned thing for my hip,” said James Moore, a UK disability activist who uses a wheelchair. “Did none of the people who contributed to this not read it through this guidance and spot any of the gaping holes in its logic? How is it that I can see them and they can’t?”

“I fear the consequences for those with unsympathetic GPs who suddenly find themselves without medication that may work for them,” Moore wrote in the Independent. “This guidance urgently needs a rethink. Sadly, there may be torture looming for those in torment before we get one.”

The NICE guideline is at odds with recent studies that found antidepressants are minimally effective as pain relievers and often have adverse side effects. A common complaint of pain patients who take duloxetine, for example, is how quickly they became dependent on the drug and have severe withdrawal symptoms when they stop taking it.

The UK guideline also differs from treatment recommendations made by U.S. health agencies. The FDA and CDC recommend gabapentinoids for fibromyalgia, and acetaminophen and NSAIDs for low back pain and migraine.   

The CDC is currently in the process of updating and possibly expanding its opioid guideline to include recommendations for opioid tapering, short-term acute pain, migraine and other pain conditions. 

How To Get Medical Help for Intractable Pain

By Forest Tennant, PNN Columnist

Americans have been trained and oriented to believe that when making an appointment with a medical provider they will walk in, discuss their health issues and receive good care. Those days are long gone if you need care for a painful disease like Intractable Pain Syndrome (IPS).

It is common for persons with IPS to forget how rare this condition is compared to more prevalent diseases such as asthma, diabetes and hypertension. Any person with IPS also has to face the sad fact that the media, government and mental health professionals have condemned and painted every person with IPS as a drug abuser who is not worthy of being trusted with an opioid, benzodiazepine or adrenaline type stimulant.

Things have gotten so out-of-hand that most doctors are afraid to treat pain for fear of government penalties or condemnation by their peers, hospital or malpractice insurance carrier. Many veterans’ hospitals and private health plans now essentially ban the prescribing of opioids.

State and federal policies also make it difficult to travel long distance to access treatment, as that may be seen as a “red flag” that a patient is doctor shopping or visiting a pill mill.

Whenever possible, persons who have IPS should pursue physicians and nurse practitioners in their local community to provide necessary care.

Here are some tips we recommend when visiting a local medical provider for the first time:

1. Do not refer to yourself as a “pain patient,” but as a person with a disease that causes pain. Tell providers what condition you have been diagnosed with: “I have adhesive arachnoiditis, neuropathy, Ehlers-Danlos Syndrome, etc.” 

2. Put together a complete set of documented medical records and bring them to every appointment, including personal identification, local address, insurance coverage, medical diagnosis, MRI’s, lab tests, and list of past treatments. Your records should be neatly organized in a 3-ring binder or file folder.

3. Know your state’s opioid prescribing guidelines and regulations. Do not ask physicians or pharmacists to violate these rules. 

4. Research and understand your disease and carry written materials about it to your medical providers.

5. Identify a local pharmacy and health food store in your community that will fill your prescriptions and carry the supplements you need. Don’t ask a doctor to find you a pharmacy.

6. Know and be able to describe the complications of your constant pain, such as hypertension, tachycardia, elevated cholesterol, diabetes, autoimmunity and hormone deficiencies.

7. Until regular care is established with a provider, a family member -- ideally a spouse -- should attend all appointments to help build credibility and assurance with the provider.

8. Know the name and dosage of every drug and supplement you take, and which ones treat the cause of your pain, suppress the pain, or treat a complication of your pain.

9. Plan on having multiple medical practitioners to treat your conditions. For example, your primary care physician may treat your hypertension or hormone deficiencies, but a neurologist may treat the pain.

10. Due to opioid restrictions, identify non-opioid substances that will substitute or potentiate whatever opioid may be available in your community. Some examples: kratom, CBD, palmitoylethanolamide (PEA), ketamine, oxytocin.

11. Develop a care plan of non-prescription agents to treat the cause of your pain, suppress inflammation and boost hormone levels. 

Know Your Diagnosis

You must have a verifiable, anatomic diagnosis that is the cause of your IPS. The fact that you have intractable pain is not sufficient. You must know the cause of it.

An anatomic diagnosis requires a physical examination plus confirmation with an x-ray, MRI, photograph, blood test, elector-conduction study or biopsy. This information must be documented in your medical record. Equally important is to keep a copy of all test results in your personal possession -- not in some doctor’s office.

Two cases offer examples of mistakes patients can make when when visiting a provider for the first time:

1) A woman consulted with us who was taking three different opioids that had quit providing pain relief. When asked what caused her pain, neither she nor her husband knew. They could not provide an answer.

2) A woman on two opioids and three ancillary agents wanted a letter to support her disability claim. When asked the cause of her pain, she didn’t know, except that her feet and legs hurt, and someone told her she might have fibromyalgia.

Neither of these patients could produce a single page of medical records stating the cause of their pain. Not surprisingly, they also couldn’t locate a doctor to help.

The following are not considered specific enough diagnoses to obtain opioids or disability: bad back, sciatica, failed back, sprain or strain, fibromyalgia, headache, accident, EDS, neck pain or pain from a fall. 

Persons who have IPS or chronic pain are usually taking several drugs, including controlled medications, but don’t always know why they are taking them. If you don’t know why you are taking a drug, you may appear to medical practitioners to simply be a drug seeker who abuses medication or has an addiction or opioid use disorder.  

If you can’t explain in detail why you take each medication, including supplements, you shouldn’t be taking them. No MD or nurse practitioner will prescribe them to you if you don’t know why you are taking them. That is why it is imperative that you learn as much as you can about each medication and supplement you are taking. 

If the only care you are seeking is for temporary, symptomatic pain relief with opioids or benzodiazepines, don’t expect to find pain care. Also, don’t expect acceptance from local practitioners unless you are taking medications to treat the cause of your pain and to permanently reduce your pain. 

Forest Tennant 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 has given financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Study Finds Little Evidence to Support Use of Acetaminophen

By Pat Anson, PNN Editor

Acetaminophen is the most widely used over-the-counter pain reliever in the world — the active ingredient in Tylenol, Excedrin, and hundreds of pain medications. The U.S. Centers for Disease Control and Prevention considers acetaminophen a “first-line” treatment for low back pain, osteoarthritis and migraine.

But a comprehensive review published in the Medical Journal of Australia found little or no evidence to support the use acetaminophen for most pain conditions. Researchers at the University of Sydney analyzed 36 studies involving over 19,000 people and concluded that the pain-relieving benefits of acetaminophen – known as paracetamol outside the U.S. -- are modest, at best.

“For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain,” wrote senior author Christopher Maher, PhD, a professor at the Sydney School of Public Health.

Maher and his colleagues looked at 44 pain conditions often treated with paracetamol, and could find only four for which there is high-quality evidence:

• Knee and hip osteoarthritis

• Tension headache

• Perineal pain after childbirth

• Craniotomy

Evidence for the other 40 pain conditions was low quality or inconclusive, including:

• Acute and chronic low back pain

• Major surgery

• Dental surgery

• Migraine

• Rheumatoid arthritis

• Hip fracture

• Cancer pain

• Neuropathic pain

“While paracetamol is widely used, its efficacy in relieving pain has been established for only a handful of conditions, and its benefits are often modest. Although some trials have evaluated regimens that may have underestimated its utility, the clinical application of paracetamol is primarily guided by low quality evidence, at best,” researchers said.  

A 2015 study in the British Medical Journal also found that paracetamol was ineffective for low back pain and provided little benefit to people with osteoarthritis.

In recent years, some U.S. hospitals have started using paracetamol as an alternative to opioids for post-operative pain, a practice not supported by the Australian study.

One limitation of the University of Sydney review is that most of the studies that were evaluated only used a single dose of paracetamol, which does not reflect its typical use.  Perhaps for that reason, researchers found that adverse events were similar for patients receiving paracetamol or a placebo.

Over 50 million Americans use paracetamol (acetaminophen) each week to treat pain and fever. Long-term use has long been associated with liver, kidney, heart and blood pressure problems. Acetaminophen overdoses are involved in about 500 deaths and over 50,000 emergency room visits in the U.S. annually.

CDC Won’t Say Who Is Writing Update of Opioid Guideline

By Pat Anson, PNN Editor

When the Centers for Disease Control and Prevention released the draft version of its opioid prescribing guideline in September 2015, the agency was roundly criticized for its secrecy and lack of transparency.

There were no public hearings. The CDC initially refused to identify who wrote the guideline or who its advisors were. And the public was given just 48 hours to comment on the guideline after a botched online webinar that presented only a summary of the recommendations.     

After a congressional investigation and threats of a lawsuit for “blatant violations” of federal laws, the CDC changed course and opened up the guideline to public scrutiny and a 30-day comment period. After a few minor changes, the guideline was released in March 2016.

Five years later, after a tsunami of complaints that the guideline’s recommended dosage limits have been harmful to patients and failed to reduce opioid addiction and overdoses, the CDC is now in the process of rewriting the guideline.

There’s more transparency this time around. The public was given an early invitation to comment and nearly 5,400 people wrote to the CDC about their concerns.  The agency also released the names of the “Opioid Workgroup,” a diverse group of physicians, academics and patients that is advising the agency as it updates the guideline.     

But one thing hasn’t changed: the CDC won’t identify who is writing the guideline update.

“Primarily CDC scientists are involved in drafting the update,” Courtney Lenard, a CDC spokesperson, explained in an email to PNN. “Many CDC staff are working on the process of updating the 2016 Guideline, including reviewing the scientific evidence; analyzing patient, caregiver, and provider input gathered during the public comment period and conversations held earlier in 2020; and drafting its content.”

The updated guideline will be only reviewed by the Opioid Workgroup, which has been given no direct role in writing it or in making revisions. The workgroup is expected to give its recommendations to the Board of Scientific Counselors at the CDC’s National Center for Injury Prevention and Control sometime this summer.

“At that time the authors of the draft Guideline will also be announced,” said Lenard, adding that the public likely won’t see the draft until late 2021, when it is published in the Federal Register.

Potential Conflicts of Interest

Only after another round of public comments will the revised guideline finally be released in 2022 – a full six years after the initial guideline. Some patient advocates worry about a lack of urgency at CDC and that too much is occurring behind closed doors.  

“I remain concerned about an ongoing lack of transparency in the development of an update to the CDC Pain Guidelines,” said Dr. Chad Kollas, a palliative care specialist in Florida. “There will be no disclosure about the authorship of the revised guidelines until their release, which effectively eliminates the opportunity to challenge any of their authors’ potential conflicts of interest proactively.”

“The CDC has put together a writing team without addressing transparency or conflicts of interest to our satisfaction,” says Terri Lewis, PhD, a patient advocate and researcher. “This is unacceptable and nonresponsive to the concerns that have been so clearly expressed by both the patient community and the medical communities since 2016.”  

The CDC’s evasive response about who is writing the update raises the possibility that the three authors of the original 2016 guideline are working on the revision: Deborah Dowell, MD; Tamara Haegerich, PhD; and Roger Chou, MD.

In 2019, the trio penned an awkward defense of the guideline in The New England Journal of Medicine, in which they admitted the “misapplication” of guideline was causing harm to patients, but deflected taking any responsibility for it.

Chou’s involvement in the updated guideline would be particularly alarming to critics, because of his advocacy for opioid tapering and collaboration with Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

“I'd give long odds that Roger Chou is a member of the current CDC writers group,” says Richard Lawhern, PhD, a prominent advocate in the pain community. “Talk about giving the fox the keys to the hen house!” 

In addition to his work on the 2016 guideline, Chou has authored numerous articles on pain management in peer-reviewed medical journals, many of them critical of opioid prescribing.

Chou is listed as an “external reviewer” on a PROP guide promoting “Cautious, Evidence-Based Opioid Prescribing” that at one time was posted — unedited — on the CDC’s website.

In 2019, Chou co-authored an article with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.”

And in 2011, Chou co-authored another op/ed with PROP founder Dr. Andrew Kolodny and PROP vice-president Dr. Michael Von Korff, calling for a major overhaul of opioid guidelines, which were then primarily written by pain management specialists.

“Guidelines for long-term opioid therapy should not be developed by the field of pain medicine alone. Rather, experts from general medicine, addiction medicine, and pain medicine should jointly reconsider how to increase the margin of safety,” Chou and his co-authors wrote, a call to action that came to pass five years later at CDC with a guideline that he helped write.

“I do not believe the CDC should be writing opioid guidelines,” says Dr. Lynn Webster, a PNN columnist and past president of the American Academy of Pain Medicine.  

“The authors of the CDC guideline should not have been tasked with creating the guideline for a few reasons. First, this was outside their areas of expertise. Second, they failed to understand how misguided arbitrary limits of morphine milligram equivalents were in recommending dosing to people in pain. Third, they lacked compassion for people in pain and an understanding that, for some patients, opioids were the only effective, available treatment.”  

Should Chou Be Recused? 

Chou is a primary care physician who heads research at the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University. He was the lead investigator for a recent report by the Agency for Healthcare Research and Quality (AHRQ) that found opioids have only “small beneficial effects” when prescribed for chronic pain and “do not appear to be superior to nonopioid therapy.”

Chou’s report, along with four other AHRQ reviews of pain therapies, were commissioned by the CDC. The reports are being used as key resources by the agency as it updates and possibly expands the opioid guideline to include recommendations for opioid tapering, short-term acute pain, migraine and other pain conditions. 

Some advocates believe Chou is so biased against opioids he should be recused from any further work on the guideline.

“I agree with that. He’s clearly published things and said things. He is not objective on dealing with people who need high dose opioids. It’s just as simple as that. He’s going to oppose anything that allows people to take opioid drugs,” says Forest Tennant, a PNN columnist and intractable pain expert. “They never put people on there who are for opioids. It’s always against.”

“Absolutely he should (be recused). Dr Chou is in the position of being given an opportunity to defend his earlier misdirected, unscientific, and ethically unsound work by influencing the revised guidelines to confirm his earlier positions. This is a ‘professional’ self-interest at least equally as meaningful of any financial relationship,” said Lawhern. 

“The harm the 2016 guideline caused should be sufficient reason to find a new group of individuals to work on the updated recommendations. Having the same authors work on the same guidelines makes it almost inevitable that the same mistakes will be made,” says Webster.

“To paraphrase Albert Einstein, it is insanity to do the same thing again and expect different results. If you want better results, you have to do something differently. I can see that the updated guideline will lack consideration for patients as individuals, just as the 2016 guideline did.”

For much of the past year, the CDC has been preoccupied dealing with fallout from the COVID-19 pandemic. The agency’s once-sterling reputation has been damaged by political interference and shifting recommendations on how to control the virus. The agency’s focus in 2021 is likely to remain on COVID-19.

Pain sufferers and their advocates worry that revising the opioid guideline will not be a top priority at CDC, and that many of the same mistakes made five years ago are being repeated.    

“There is no indication that CDC is treating this with the respect it deserves or with the scientific rigor it demands in spite of mounting evidence that the management of prescription opioids in the USA is 'going off the rails' and that very real systemic and structural harms are accruing to patients and the health care delivery system in general,” says Terri Lewis. 

“I think it fair to say that we all fear that, based on what we are aware of at the moment, this next round of 'revision' will simply amount to an 'expansion' into territory for which there is almost no verifiable evidence and very weak support in the existing literature.”

Why President Biden Must Act on Stem Cells

By A. Rahman Ford, PNN Columnist

In a recent Forbes article, Jake Becraft argues that biomedical manufacturing must receive similar federal investment as technology infrastructure if all Americans are to have equitable access to emerging medical technologies like stem cell therapy.

Becraft notes that -- unlike the rollout of 5G wireless technology, which received substantial public and private investment -- healthcare distribution bottlenecks have received much less attention.

 “If 70% of Americans should have access to 5G, why shouldn’t they also have access to live-saving therapeutics?” asks Becraft, who is the founder and CEO of Strand Therapeutics. “What good is gene therapy to cure blindness if only those with an extra $850,000 in their pocket and home near an urban center can access it?

“If we invest in the fair and equitable distribution of life-saving therapeutics across the country, and not just in the medical hubs of major cities, we could make cell and gene therapies as accessible as we have aimed to make 5G. Cures shouldn’t exist only for the privileged.”

For Becraft, true next-generation health access requires a revolutionizing and re-imagining of healthcare manufacturing and delivery, which would consequently speed the development of cell therapies.

A Broken Stem Cell Infrastructure

Becraft’s argument cuts to the heart of the stem cell accessibility divide, which is especially true with regard to autologous stem cells that are derived from a patient’s own body fat, bone marrow and other tissues.

Harvesting, processing and administering autologous stem cells is relatively simple, cheap and can be done in one day.  Clinicians around the world have been using these therapies to treat or even cure autoimmune diseases and orthopedic problems that are often poorly treated with conventional medical modalities,

But autologous stem cells are currently heavily regulated in the U.S. because the Food and Drug Administration considers a person’s own stem cells to be “drugs” and thus subject to the long, arduous and expensive clinical trial process.

Other countries have more relaxed stem cell regulations. This means that professional athletes and wealthy people can simply fly to Europe or Columbia to receive potentially life-saving therapy. Meanwhile, the average American – many of whom are financially devastated by COVID-19 – is left to languish and suffer.

Clearly, the incrementalism and gradualism that has for too long pervaded and permeated medical technological progress must give way to thoughtful, purposeful and conscious revolutionary reconsideration.

A ‘New Deal’ for Stem Cells

Up to this point in his nascent administration, President Biden has not made stem cell accessibility and affordability a priority. Yes, there are several clinical trials underway for stem cell candidates to treat the symptoms of COVID-19. And, to the FDA’s credit, these trials are being expedited.

But thick federal bureaucratic fog still stifles the commercialization of emerging stem cell modalities that Americans in pain so desperately need. The FDA has yet to approve a single stem cell product as a treatment for arthritis or any orthopedic condition.

Almost one year ago, I wrote that then FDA Commissioner Stephen Hahn had the opportunity to implement a stem cell “New Deal” that would provide much-needed clarity to the regulatory landscape by vesting the states with primary authority over autologous stem cells.

The “New Deal” baton has now been passed from the Trump administration to President Biden, who can help lead us the finish line of stem cell accessibility and affordability. His administration has an opportunity to make good on its pledge to do right by the American citizenry it has pledged to serve. President Biden, the American people are counting on you.

A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor-in-Chief of the Howard Law Journal. Rahman lives with chronic inflammation in his digestive tract and is unable to eat solid food. He has received stem cell treatment in China. 

The Pain Community Needs More Unity and Awareness

By Carol Levy, PNN Columnist

My column last month, “It’s Time for People in Pain to Be Heard,” received a lot of comments on PNN and in social media.

Most often the writer wrote about why or how they had been hurt by the implementation of the CDC opioid guideline. Several people commented that it’s not because they're too busy to become involved, they’re just in too much pain to advocate for themselves.

One poster told the story of a recent pain rally held at their state capitol. It was a real-life case of what if you threw a rally and no one came? Only one person showed up, defeating the point of the rally. The writer did not mention how many had said they would be there, but I imagine the number had to be more than one.

Yes, the pain stops us from doing many things. Yes, our complaints about how the battle against opioid prescriptions has made us the bad guys, has scarred us, and made our lives so much harder are true. But saying it only on PNN, Twitter, Facebook and other social media sites does not help the cause.

It helps us and only us, by giving us an outlet to express our anger and frustration about how our minds and bodies are affected when our medications have been reduced or stopped. The problem is that by speaking out only among ourselves, the rest of the world hears silence.

When we say the pain is what keeps us from going out and protesting, maybe we need to look at the many walks against cancer, Alzheimer's, multiple sclerosis and other diseases. Many of the people involved in those walks are not the patients themselves, who often cannot participate because of their illness. It is their family, friends and colleagues.

What if we worked to marshal our families, our friends and our colleagues to march for us?

Most people do not understand what chronic pain is or that it comes in many different forms. They are not educated about Complex Regional Pain Syndrome (CRPS), trigeminal neuralgia and other cranial neuropathies, Ehlers Danlos, and many other diseases and disorders that have essentially claimed our lives.

We have many “Awareness” days. For example, the first Monday of November each year is CRPS Awareness Day; October 7 is Trigeminal Neuralgia Awareness Day; and May is Ehlers Danlos Awareness Month. We who have the disorders may be aware of these days, but how many people in the general population don't know the day or month exists, much less what the disorder is?

To many people, “chronic pain” is merely pain that lasts a long time. CRPS or trigeminal neuralgia are chronic, progressive and often incurable, but to those who are not educated about them, they’re more like a stubborn toothache or ankle sprain that won’t go away.

What if on awareness days we inundate Congress, the news media and social media with letters, emails and tweets? What if we acted as a true group, not individual voices in the wilderness, but as a harrowing cry? Maybe then our voices would finally be heard.

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.

FDA Updates Import Alert for Kratom

By Pat Anson, PNN Editor

Federal health officials may have dropped plans to schedule kratom as a controlled substance, but that’s not stopping the Food and Drug Administration from updating an import alert that gives the agency broad powers to seize shipments of the herbal supplement.

The alert targets dozens of kratom exporters and importers in the United States, Canada, Indonesia, Malaysia and the Philippines, and allows FDA inspectors to detain “without physical examination” dietary supplements and ingredients that contain kratom.  In an email, an FDA spokesperson told PNN the alert was updated for “minor changes” involved with one firm’s listing  

Kratom is an herbal supplement that comes from the leaves of a tree that grows in southeast Asia, where kratom has been used for centuries as a natural stimulant and pain reliever. In recent years, millions of Americans have discovered kratom, using it to self-treat their chronic pain, anxiety, depression and addiction.

The FDA says it has “serious concerns” about kratom because of its opioid-like properties.

“Consumption of kratom can lead to a number of health impacts, including respiratory depression, nervousness, agitation, aggression, sleeplessness, hallucinations, delusions, tremors, loss of libido, constipation, skin hyperpigmentation, nausea, vomiting, and severe withdrawal signs and symptoms,” the alert warns.

The FDA issued its first import alert for kratom in 2012, just as kratom was gaining in popularity in the U.S. Since then, several large shipments of raw kratom or kratom supplements have been seized. One of the largest seizures was in 2018, when 28 tons of kratom were confiscated at a South Carolina warehouse operated by Earth Kratom, a kratom wholesaler and vendor. The kratom was later incinerated.   

Kratom can be sold legally in most U.S. states, but vendors can run into trouble if they claim it can be used to treat medical conditions or market it as a dietary supplement.

A lobbyist for the American Kratom Association, an association of kratom vendors and consumers, said the updated alert is part of the FDA’s “disinformation campaign” against kratom.

“The FDA routinely uses the import alerts in discussions with various stakeholders to highlight their claims that kratom is not ‘legally marketed’ in the United States, and by adding a recent date by way of an update makes it appear to be a recent action,” said Mac Haddow. “The import alert is an abuse of that authority that is supposed to apply to contaminated and adulterated products.

“In fact, the objections listed in the import alerts issued by the FDA technically only apply to importers who are subsequently making illegal therapeutic claims or as a dietary supplement on marketing materials. A bulk kratom importer is not subject to FDA's authority. Kratom processors who make no claims and sell kratom as a food are not subject to any pre-market approval by the FDA.”

Federal efforts to ban kratom in 2016 failed due to a public outcry. Two years later, federal health officials quietly withdrew their request to classify kratom as a Schedule I controlled substance because of “lack of evidence” it can be abused or posed a public health threat. The FDA, however, still maintains “significant potential safety concerns” about kratom. 

A 2020 study funded by the National Institute on Drug Abuse concluded that kratom is an effective treatment for pain, helps users reduce their use of opioids, and has a low risk of adverse effects.

Positive Results From Stem Cell Trial for Knee Osteoarthritis

By Pat Anson, PNN Editor

A California stem cell company has announced positive results from a small, early-stage clinical trial of an experimental stem cell therapy for knee osteoarthritis.  

The Phase 1/2a trial conducted by Personalized Stem Cells (PSC) involved 39 patients with knee osteoarthritis who were given a single injection of autologous mesenchymal stem cells derived from their own body fat. Safety was the primary objective of the trial and there were no serious adverse events reported by the company.

The secondary objective of the trial was to assess the effectiveness of the therapy with the Knee Injury and Osteoarthritis Outcome Score (KOOS), a survey that asks patients about their pain, other symptoms, daily function, quality of life, and recreational activities. Nearly 80% of study participants improved above the “minimal important change” (MIC), with an average improvement over baseline of 2.2 times the MIC.

Osteoarthritis is a progressive joint disorder caused by painful inflammation of soft tissue, which leads to thinning of cartilage and joint damage in the knees, hips, fingers and spine.

Results from the PSC study have been submitted to the FDA for review. The company hopes to get approval for a larger, Phase 2 randomized study of its stem cell therapy later this year.  

“We are pleased at the strong safety profile and efficacy results in this FDA-approved clinical study of stem cell therapy for knee osteoarthritis,” said PSC founder and CEO, Dr. Bob Harman. “We are proud to have reached this milestone in our first FDA approved clinical trial. This data supports our progress in the larger placebo-controlled clinical study.”

Veterinarians Already Using Stem Cells

While the FDA has approved hundreds of clinical trials of stem cells, it has not approved a single stem cell product as a treatment for arthritis or any orthopedic condition. That hasn’t stopped stem cell clinics from offering regenerative medicine to patients or veterinarians from using it on animals.

VetStem Biopharma, the parent company of PSC, pioneered the use of adipose derived stem cells in veterinary medicine. Its laboratory has processed stem cells for nearly 14,000 dogs, cats, horses and other animals for use by veterinarians in the U.S. and Canada.

“The 15 years of veterinary experience with adipose derived stem cell therapy of our parent company, VetStem Biopharma, provided the basis for our FDA study submission and approval and provided valuable insights into the study design and conduct,” said Harman.

In addition to the Phase 2 trial for osteoarthritis, PSC plans to pursue FDA approval for a stem cell trial to treat traumatic brain injuries in humans. A clinical study using PSC’s stem cell platform to treat respiratory distress syndrome in COVID-19 patients is currently underway.