9.6 Million Counterfeit Pills Made with Fentanyl Seized in 2021

By Pat Anson, PNN Editor

Seven years after the Drug Enforcement Administration issued its first nationwide alert about the emergence of illicit fentanyl in street drugs, the fentanyl crisis continues to escalate and overdose deaths keep rising.

A new study by the National Institute of Drug Abuse (NIDA) estimates that 2,416 kilograms (5,326 pounds) of illicit fentanyl powder were seized by U.S. law enforcement agencies in the last three months of 2021. According to a DEA estimate of fentanyl’s lethality, that’s enough to kill 1.2 billion people.  

That’s not the worst part, according to researchers. The number of counterfeit pills made with fentanyl is also growing and now make up about 29% of all seizures. Over 9.6 million counterfeit pills were seized by law enforcement last year.

“An increase in illicit pills containing fentanyl points to a new and increasingly dangerous period in the United States,” NIDA Director Nora Volkow, MD, said in a statement. “Pills are often taken or snorted by people who are more naïve to drug use, and who have lower tolerances. When a pill is contaminated with fentanyl, as is now often the case, poisoning can easily occur.”

In the last quarter of 2021, over two million counterfeit pills laced with fentanyl were seized – a 4,850% increase from the same period in 2018.

Counterfeit pills are particularly worrisome because they are easy to manufacture, transport and sell -- and most people who buy them have no idea if they’re getting a potentially lethal dose of fentanyl. Counterfeit pills known on the street as “Mexican Oxy” or “M30” look nearly identical to 30mg oxycodone pills.

Because fentanyl is up to 100 times more potent than morphine and 50 times more potent than heroin, it doesn’t take much to kill someone. The DEA estimates that nearly half of counterfeit pills contain at least 2mg of illicit fentanyl, a potentially lethal dose.

“What is particularly concerning is that fentanyl is now often pressed into counterfeit pills which resemble oxycodone (e.g., blue “M30″ pills), hydrocodone, or benzodiazepines such as alprazolam. This is alarming because a large portion of people who misuse psychoactive prescription pills such as opioids or benzodiazepines obtain them from nonmedical sources, thus increasing the likelihood of users unintentionally ingesting fentanyl through counterfeit pills,” lead author Joseph Palamar, PhD, a drug epidemiologist at NYU’s Grossman School of Medicine, reported in the journal Drug and Alcohol Dependence.

Illicit fentanyl was first detected in cocaine, heroin and other U.S. street drugs in 2014. Two years later, counterfeit pills made with fentanyl also began appearing, around the same time the CDC released a guideline that discourages doctors from prescribing opioids for chronic pain.

Faced with pressure from Congress to crackdown on painkillers, the DEA began reducing the legal supply of opioids in 2017. The agency has reduced opioid production quotas for five consecutive years, cutting the supply of hydrocodone and oxycodone in half.

In 2021, the DEA quietly acknowledged that drug cartels were actively targeting pain sufferers as potential customers.  A DEA report said nearly two-thirds of people who misused pain medication “identified relieving pain as the main purpose” of their drug use.

Cutting back on legal opioid medication has clearly backfired. The CDC recently reported that over 105,000 Americans died of drug overdoses in the 12-month period ending October 2021, a record number. About two-thirds of those deaths involved synthetic opioids such as fentanyl.

The risks of fentanyl and counterfeit pills should be well-known by now, but Palamar and his colleagues say a surprising number of people are oblivious to the danger. They cited a recent study of nightclub attendees – a group at high risk of illicit substance use – which found that only half were aware that pills obtained from family, friends or dealers may be counterfeit versions made with fentanyl.

“Public education about the risk of non-pharmacy-sourced pills containing fentanyl needs to be more widespread,” they wrote. “These findings suggest that a substantial portion of people who use illegal drugs appear to be aware that non-pharmacy-sourced pills can contain fentanyl, but less experienced people who may be at risk for use require more education.”

Should the CDC guideline be changed to make it easier for doctors to prescribe opioids? Let us know what you think by taking PNN’s survey on the revised CDC guideline. Click here to get started.

U.S. Falls to 8th Globally in Per Capita Opioid Sales

By Pat Anson, PNN Editor

Concerns about opioid addiction and overdoses have caused opioid sales to plummet in the United States in recent years. Opioid consumption has fallen so sharply that Canada, Australia and several European countries have overtaken the U.S. and become the highest consumers of opioid analgesics, according to a new study.

But in many poor and middle-income countries, access to opioids remains very limited, causing unnecessary pain and suffering for millions of sick and dying people.

“There are still concerningly low rates of opioid use in large parts of the world, even in numerous middle-income countries,” said lead author Wallis Lau, PhD, a Lecturer at the School of Pharmacy, University College London.

“Opioids have been listed by the World Health Organization as an essential class of medicine for acute pain, cancer-related pain, and palliative care since 1977, so it is troubling that in many parts of the world, people are unable to access this medicine. There is an urgent need to tackle the global gap in opioid access.”

Lau and her colleagues analyzed global pharmaceutical sales in 66 countries from 2015 to 2019. They found that opioid use in some African and South American countries was less than one tenth of 1% of the rates in wealthier countries in North America, Europe and Australia, according to findings published in The Lancet Public Health.

The highest opioid rate was found in Canada, estimated at 988 milligram morphine equivalents (MME) per day for every 1,000 people. That was down from an average of 1,581 MME per day in Canada in 2015.

By comparison, the U.S. rate was 738 MME per 1,000/day, a 45% decline since 2015. Long touted as having the highest per capita opioid consumption in the world, the U.S. now ranks 8th globally in opioid sales.

At the other end of the scale, a group of 12 West African countries reported only 0.01 MME per 1,000/day. A few other countries, including three in South America, reported rates below 1 MME per 1,000/day.

Opioid Sales Per Capita (2019)

SOURCE: THE LANCET

Researchers say the disparities in opioid consumption go beyond factors such as a nation’s wealth, healthcare quality and disease prevalence. For example, wealthy countries such as the United Arab Emirates and Saudi Arabia reported very low rates of opioid use. Kazakhstan also reported low rates of opioid consumption, despite having high cancer prevalence and high cancer death rates.

“Some countries have low opioid analgesic consumption despite a high cancer prevalence, which could suggest inadequate access to opioid analgesics as much-needed pain control,” said Lau.

Overall, global opioid sales increased by 4% annually from 2015 to 2019. Opioid consumption rates increased in most areas that reported low use, including Eastern Europe, Asia, and South America, but not in Africa.

“These findings reinforce the need to recognise palliative care and pain relief as a global public health priority. In countries that already have good access to opioid analgesics, it is important to avoid opioid misuse and overprescribing, without leaving patients undertreated.” said co-senior author Professor Ian Wong of UCL School of Pharmacy and University of Hong Kong.

According to a 2017 international study commissioned by The Lancet, over 25 million people die annually in severe pain because they have little or no access to morphine and other painkillers. Another 35 million people live with chronic pain that is untreated. The Lancet commission said there were several barriers that stood in the way of effectively treating pain, including “opiophobia” – prejudice and misinformation about the medical value of opioids.

“Unbalanced laws and excessive regulation perpetuate a negative feedback loop of poor access that mainly affects poor people,” the commission said.

Therapy Dogs Reduce Pain in ER Patients

By Pat Anson, PNN Editor

Pet therapy has long been used in a variety of medical settings to help patients feel better – from nursing homes and hospice care to pediatric wards and cancer centers. And now, for the first time, there’s evidence that therapy dogs can significantly reduce pain, anxiety and depression in emergency department patients.

A Canadian research team at the University of Saskatchewan randomly selected nearly 200 ED patients who were waiting to be treated or admitted at Saskatoon's Royal University Hospital. Half of the participants spent 10 minutes with a therapy dog and its handler, while the other half received standard care without a dog visit.

The study findings, recently published in PLOS ONE,  showed that nearly half the patients visited by a therapy dog reported a decrease in pain (43%), with similar improvements in anxiety (48%), depression (46%) and overall well-being (41%). The dog visits had no significant effect on heart rate or blood pressure.

“Clinically significant changes in pain as well as significant changes in anxiety, depression and well-being were observed in the therapy dog intervention compared to control. The findings of this novel study contribute important knowledge towards the potential value of ED therapy dogs to affect patients’ experience of pain, and related measures of anxiety, depression and well-being,” wrote lead author Colleen Dell, PhD, a sociology professor at the University of Saskatchewan.

Pain is the most common reason that someone visits an emergency department, so the finding that therapy dogs can decrease pain levels is notable – particularly because most patients in the study (77%) did not receive any pain medication.

Many people with pain dread the idea of going to an emergency room, fearing that their pain won’t be treated properly. In a PNN survey of nearly 1,300 acute and chronic pain patients, over 80% said hospital staff are not adequately trained in pain management and over half rated the quality of their pain care in hospitals as poor or very poor. Nearly eight out of ten patients felt they were labelled as an addict or drug seeker by hospital staff.

Dell and her colleagues are well aware of the stress a pain patient can experience when visiting an emergency department, particularly in an era when the use of opioid medication is discouraged. Long waits, bright lighting and high noise levels may also make it difficult for ED patients to relax. They think therapy dogs could be useful in improving the patient experience.

“With adequate access to pharmaceutical pain management a concern for ED patients, as well as long wait times, it will be important to explore creative, non-pharmaceutical options,” said Dell. “Patient waiting has also been associated with negative emotional states and well-being in ED patients. Negative feelings, particularly anxiety and stress, can be intensified when patients encounter uncertainty regarding their pain.

“The role of therapy dog visits in decreasing patients’ perceived pain, whether as a distraction or by some other mode, is an important finding that should be examined further in both practice and research.”      

The benefits of having a pet are well known to most pet owners. A 2019 survey of over 2,000 older Americans found that pets helped them enjoy life, made them feel loved, kept them physically active and reduced stress. Pet ownership was particularly helpful to those who rated their health as fair or poor. More than 70 percent of those older adults said pets help them cope with physical or emotional problems, and nearly half (46%) said their pets help distract them from pain.

Medical Cannabis Is Losing Credibility

By Roger Chriss, PNN Columnist

As more and more states legalize medical cannabis for chronic pain, anxiety, seizure disorders and other common medical conditions, the question of efficacy becomes increasingly important. Recent studies show a lack of efficacy, but so far states are not modifying their list of approved conditions for medical cannabis.

Many states approved cannabis for medical conditions without good evidence. California legalized medical marijuana in 1996, yet nearly three decades later the Medical Board of California is still advising physicians that “there is a lack of evidence for the efficacy of cannabis in treating certain medical conditions.”

We not only still lack evidence, but new research suggests that cannabis doesn’t help and may actually be harmful:

• A small randomized trial in Boston found no significant improvement in pain, anxiety or depression in people given medical marijuana cards, but a higher risk of developing cannabis use disorder.

• A matched cohort study in Hawaii on people 50 or older saw a “significantly greater risk of coronary heart disease, chronic non-cancer pain, stroke, myocardial infarction, cyclic vomiting, and injuries” in people using cannabis compared to non-users.

• An observational study in New York of 29 people with epilepsy given two formulations of cannabidiol (CBD) and tetrahydrocannabinol (THC) concluded that “we found no evidence of efficacy… in treating epilepsy, sleep, or behavior in our population.”

Recent reviews of past studies are similarly disappointing.

• A review of 16 studies of CBD for mental health disorders found that “there is currently not enough high-quality evidence to suggest the clinical use of CBD for any psychiatric disorder.”

• A systematic review of 28 studies on medical marijuana for multiple sclerosis concluded that “the magnitudes of effects on short-term neurological outcomes in MS patients are either small, limited, or moderate.”

Lack of Efficacy

The 2017 National Academies report on cannabis noted the need for more research. Since then, over 6,400 studies have appeared on PubMed on medical cannabis specifically, and a total of 12,100 studies on cannabis in general. More studies are forthcoming, including 460 clinical trials of cannabis that are active or recruiting.

The result so far is a growing body of high-quality studies and clinical trials published in major journals showing a lack of efficacy and a risk of poor outcomes for conditions that cannabis is state-approved for.

Ordinarily, states follow the laws and regulations of the Food and Drug Administration, recommendations from medical societies, and research findings and other sources of major reviews. With almost any other substance with such a weak track record, there would have been a reassessment by now. But not with cannabis.

California still approves medical cannabis for glaucoma, even though the American Academy of Ophthalmology is against it due to lack of efficacy. California is not alone. So far, no state has removed any condition from its approved list for medical cannabis use.

However, the conditions of using cannabis are changing. Some states now require patients in pain management programs to have their urine tested for cannabinoids. Many medication management agreements – known as “pain contracts” – also expressly forbid cannabis use even if it has been legalized in that state. Some medical specialties tell patients to simply avoid cannabis because of risks from drug interactions and contraindications.

Although cannabis may be safer than some prescription drugs, that won’t matter if it has no demonstrable benefit. Cannabis is losing credibility as a therapeutic as studies show poor outcomes for diagnoses that states approve cannabis for.

Holding cannabis to the same standards as other therapeutics would increase confidence in cannabis where it is shown to be beneficial. It will also help improve patient outcomes. As it stands now, however, medical cannabis is starting to look more like medicinal alcohol during Prohibition than a credible therapeutic for 21st-century medicine.

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. 

New CBD Drug Developed for Postoperative Pain

By Pat Anson, PNN Editor

An investigational drug containing a fast-acting formula of cannabidiol (CBD) reduced postoperative pain in patients after shoulder surgery, according to small new study.

Patients who took ORAVEXX tablets after minimally invasive rotator cuff surgery had an average of 23 percent less pain after the first day of surgery than those taking a placebo, according to researchers at NYU Langone Health. The tablets are designed to quickly dissolve in the mouth and the CBD absorbed into the bloodstream in less than 3 seconds.

“There is an urgent need for viable alternatives for pain management, and our study presents this form of CBD as a promising tool after arthroscopic rotator cuff repair,” says lead investigator Michael Alaia, MD, associate professor in the Department of Orthopedic Surgery at NYU Langone Health.

“It could be a new, inexpensive approach for delivering pain relief, and without the side effects of anti-inflammatory drugs like NSAIDs and addiction risks linked to opiates. Additionally, CBD has the benefit of pain relief without the psychotropic effects associated with THC or marijuana.”

There are a few caveats about the study. First, only 99 patients were enrolled in this early-stage Phase 1/2 trial. They were divided into two groups: one group took 50 mg of CBD in ORAVEXX tablets three times a day for 14 days, while the other group received a placebo or 25 mg of CBD during the study period.

Importantly, patients in both groups were also prescribed opioids, a low dose of Percocet, and told to wean themselves off the medication as soon as possible.

There were no major side effects reported by either group, but the group receiving 50 mg of CBD reported less pain and greater satisfaction in their pain control.

ORAVEXX is manufactured by Orcosa, which has developed a proprietary drug delivery system called the RITe Platform. The company says it buccal tablets dissolve so quickly in the mouth that fewer active ingredients are needed for a medication to work.

In addition to postoperative pain, the company is also planning studies to evaluate ORAVEXX as a treatment for acute and chronic pain, osteoarthritis pain and inflammation. While the initial results are promising, researchers say it could be years before ORAVEXX is available.

“Our study is examining a well-designed, carefully scrutinized product under an investigational new drug application sanctioned by the FDA. This is currently still experimental medicine and is not yet available for prescription,” said Alaia, who presented the initial findings this week at the annual meeting of the American Academy of Orthopaedic Surgeons.

Better Pain Treatment Needed for People with Severe Mental Illness

By Pat Anson, PNN Editor

There is an urgent need to improve the way pain is diagnosed and treated in people with severe mental illness, according to a new review by UK researchers.

Depression and pain commonly co-exist, with pain prevalence in people with depression estimated at 65 percent. Pain is also experienced by 29% of people with bipolar disorder, about double that of healthy people.

But while the association between pain and mental illness is well-established, researchers say pain is not routinely assessed and managed in people with SMI, due in part to discrimination by healthcare providers. Mental health problems carry a fair amount of stigma – just like pain itself -- which impedes treatment.

“Healthcare professionals underestimate pain in the presence of perceived ‘psychosocial’ problems, making discounting of pain in people with SMI particularly likely. Indeed, there is evidence that they experience diagnostic overshadowing for physical healthcare,” lead author Whitney Scott, PhD, Kings College London, reported in PAIN, the official journal of the International Association for the Study of Pain (IASP).

“In addition to limiting treatment access, pain-related invalidation, stigma, and discrimination exacerbate distress. Investigation is needed to understand the impact of intersecting experiences of stigma and discrimination in people with SMI and pain, and how to address these.”

Scott and her colleagues say there is limited knowledge about the effectiveness of pain treatments in people with SMI because they are often excluded from clinical trials due to their perceived “complex mental health needs.”

Even when pain is diagnosed, providers may be reluctant to prescribe analgesics to people with SMI because it may interact with mental health drugs they are already taking.

“Pharmacological management of pain in SMI is complicated by the potential for harmful side effects and interactions with psychotropic medications and the underlying mental health condition,” said Scott. “Antidepressants, including serotonin-noradrenaline reuptake inhibitors, are effective for pain management in the absence of depression and of course may improve co-morbid depression; however, unopposed anti-depressants may destabilise mood in bipolar disorder. Collaborative pharmacological and psychological care for comorbid pain and major depression is promising, but scarce.”

Little is also known about the effectiveness of non-pharmacological pain treatments, such as exercise and physical therapy, because people with SMI often experience isolation, fatigue and mood disorders, making them harder to motivate.  

To overcome these barriers, Scott and her co-authors say pain and mental healthcare need to be more fully integrated, with caregivers, mental health professionals, pain specialists and policymakers working together to enable more personalized care and understanding of the needs of people with SMI.

Chronic Pain Worsened for Many During Pandemic

By Pat Anson, PNN Editor

Nearly nine out of ten people with chronic pain say their symptoms have either not improved (51%) or gotten worse (36%) during the pandemic, according to a new Harris poll that found nearly half of respondents (44%) experienced delays in getting treatment due to Covid-19.

The online survey of 810 U.S. adults with chronic back or leg pain was conducted in October and November 2021. It was commissioned by Medtronic, which makes spinal cord stimulators and other neuromodulation devices that treat pain.

Nine in ten pain sufferers said pain impacts their lives on a daily basis, with poor sleep (63%) being the most common reported problem. Pain also negatively affects their mental health (60%), exercise habits (53%), mobility and function (51%), ability to enjoy hobbies (44%), social life (32%) and occupation (33%).

Over one in five (22%) said pain impacts their romantic relationships, including being intimate with a partner or spouse.

"This data bears out what we've heard from our clinician customers and patients for two years – the pandemic has been especially hard on those with chronic pain," Charlie Covert, Vice President & General Manager of Interventional Pain Therapies at Medtronic, said in a press release.

The survey found that nearly one in five pain sufferers (17%) said they have canceled a medical appointment or procedure without rescheduling, with the primary reason being fear of Covid-19 exposure. Only a third of surveyed patients (34%) feel comfortable going into a healthcare facility, and 5% say they will never feel comfortable returning to their provider.

The overwhelming majority of respondents (90%) wish there were more treatment options available to manage their pain. While most are aware of traditional treatments such as physical therapy and oral pain relievers, far fewer are familiar with options such as targeted drug delivery (38%) or spinal cord stimulation (34%).

"There is a tangible human cost to deferred procedures and delayed care. As COVID-19 hopefully begins its transition to a more endemic disease, we expect many of these patients to urgently seek relief through new or more effective treatment modalities,” said Covert. “Our survey demonstrated that an overwhelming majority want more treatment options, yet awareness of spinal cord stimulation and targeted drug delivery options remains relatively low."

The pandemic continues to affect the bottom line for Medtronic. Last month, the company said revenue losses were in the “low-double digits” for its neuromodulation and pain therapy devices.

In a conference call with analysts, Medtronic said the surge of omicron infections in January created “acute periods of worker absenteeism” with its customers, suppliers and staff. While conditions are improving, the company expects pandemic-related issues such as inflation, supply chain issues and healthcare worker shortages to linger.

Study Warns of ‘Kratom Use Disorder’

By Pat Anson, PNN Editor

Nearly a third of people who use the herbal supplement kratom develop symptoms of withdrawal and tolerance that could be signs of kratom use disorder (KUD), according to a small survey by the National Institute on Drug Abuse. Withdrawal symptoms included gastrointestinal upset, restlessness, anxiety, irritability and fatigue.

Kratom comes from the leaves of a tree that grows in Southeast Asia, where it has been used for centuries as a natural stimulant and pain reliever. An estimated two million Americans use kratom to self-treat their pain, depression, anxiety and addiction.

NIDA researchers recruited 129 past and current kratom users in the U.S. to participate in the online survey, asking them about their symptoms and demographic information.

The study findings, recently published in the Journal of Addiction Medicine, found that over half of kratom users showed no signs of addiction. But 29.5% met the diagnostic criteria for KUD, such as increased use, tolerance, withdrawal, unsuccessful attempts to quit, and craving. Most reported KUD symptoms that were mild or moderate, with about one in four with KUD having severe symptoms.  

Nearly 10% of participants also reported “psychosocial impairments,” such as decreases in social, occupational, or recreational activities because of their kratom use.

“As assessed here, tolerance and withdrawal are primary KUD features rather than psychosocial impairments. As kratom is often used among persons with a myriad of health conditions, clinicians should be aware of and assess for kratom use and withdrawal,” wrote lead author Kirsten Smith, PhD, who heads much of the kratom research at NIDA.

Federal health officials have long taken a dim view of kratom and made unsuccessful attempts to ban it. In 2018, former FDA Commissioner Scott Gottlieb, MD, claimed that kratom was an opioid, addictive, and should not be used to treat any medical condition.

“Kratom use disorder” is a relatively new diagnosis and does not appear often in medical literature.  One of the first references to it is in a 2019 study that called kratom an “emerging public health threat.” Researchers said healthcare providers need to be aware that kratom use was “typically accompanied by increasing tolerance and dependence making it highly problematic.”

A kratom advocate said the new NIDA study shows the risk of kratom addiction is low and that symptoms are often mild. 

“I thought the results of this research were particularly interesting because of the growing number of addiction recovery centers expanded their service-for-hire to include kratom use disorder (KUD) and characterizes this condition as mirroring opioid use disorder (OUD) that requires intensive drug interventions of different substances,” said Mac Haddow, a lobbyist and Senior Fellow for the American Kratom Association, which represents kratom vendors and consumers.  

“Importantly, the study concludes that tolerance of kratom over time, and withdrawal from that level of dependence are the primary outcomes rather than psychosocial impairments that are largely debilitating among drug addictions. The study also recognizes that kratom continues to be a harm reduction alternative for those suffering from polydrug use addiction issues and that accounts for its increasing use as the drug overdose crisis deepens in the U.S.” 

Kratom is often used as a treatment for addiction. A 2016 PNN survey of over 6,400 kratom users found that nearly 12% used it to reduce their cravings for alcohol or opioids. Nine out of ten said kratom was “very effective” at treating their substance use disorder. And over 98% of all respondents don’t believe kratom is harmful or dangerous.

A Pained Life: Living Unseen

By Carol Levy, PNN Columnist

AARP Magazine recently had an interview with Michael J. Fox, the actor who has Parkinson's disease. Fox spends much of his time working to teach others about the disease.

“I am a motivator and someone who tries to demystify and normalize Parkinson's - to take away any shame or sense that it should be hidden. Because unfortunately, it will inevitably reveal itself,” Fox said.

I read those words and thought, how can the pain community do this? Is there any way we can demystify and reveal what chronic pain is like? My answer is invariably, no.

Pain does not reveal itself easily to others, absent people in pain grimacing, making painful sounds (“Ouch, that hurts!”) or being vocal about their pain (“I can't go, because of my pain.”) Often those behaviors are seen as dramatizing, being lazy or a hypochondriac.

I contrasted this with a recent cooking competition I watched on TV. Prior to entering the studio cooking area, the contestant chef said, “I recently hurt my shoulder.” He added that he hoped the pain would not affect his performance. And it didn't.  He won.  

Afterwards the contestant said, “I didn't notice the pain in my shoulder until after the round was concluded, although the pain was there the entire time.”

No host or judge was there to comment, but I wondered. When he said he had pain, it was just accepted. There was no one in the wings asking, “How can it be you had the pain but could still function in the kitchen?” or “If your pain is so bad, how were able to get past it?”

Or, had he lost the contest, someone might have asked, “Did you intend to use your shoulder pain as an excuse if you lost?”

I come back to this issue -- the invisibility of our pain -- because other disorders like Parkinson’s have visibility. You can see how they impact the lives of Michael J. Fox and others.  

I wrote in a recent column about my experience of being “mask shamed” for not wearing a mask at a hospital. The week after that incident, I was mask shamed again by a conductor on a train into Philadelphia for refusing to mask.

While masks are mandated on public transportation, there are exemptions for certain groups of disabled. Because I have trigeminal neuralgia, I fall into one of those groups.  I bring this up because, when I talked with a manager, I found myself in a small debate with him.

“Had I had an oxygen tank with me, there would have been no issue. The conductor would not have done what she did,” I said.

The manager responded, “Well that is a very different situation.”

“Why is that? That person can’t wear a mask and I can’t mask either.”

“But you can see the reason for why she can't mask,” he replied.

I found myself having to educate him in the only way we can.

“If I had cancer, diabetes or heart disease, you can see none of those but that doesn’t mean I don’t have them.”

He was quiet for a moment. “Oh yeah, I see your point.”

“I am invisible, understand, simply because people refuse to see me,” wrote Ralph Ellison in the Invisible Man. “When they approach me they see only my surroundings, themselves or figments of their imagination, indeed, everything and anything except me.”  

Ellison was writing about being unseen as a person of color, but the description defines pain sufferers as well. 

Maybe, when we try to explain our invisible illness, we need to point out the obvious, as Akiko Busch did in her book, How to Disappear: “The entire world is shining with things we cannot see.”

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.

Study Warns of High Risk of Addiction in Medical Marijuana Users

By Pat Anson, PNN Editor

Medical marijuana is often touted as a treatment for chronic pain, but a new clinical trial found cannabis provided no significant improvement to people who took it for pain, anxiety or depression. Marijuana did help people sleep better, but it also raised their risk of cannabis use disorder (CUD).

“There have been many claims about the benefits of medical marijuana for treating pain, insomnia, anxiety and depression, without sound scientific evidence to support them,” says lead author Jodi Gilman, PhD, with the Center for Addiction Medicine at Massachusetts General Hospital (MGH). “We learned there can be negative consequences to using cannabis for medical purposes. People with pain, anxiety or depression symptoms failed to report any improvements, though those with insomnia experienced improved sleep.”

Gilman and her colleagues enrolled 186 people in the study and randomly assigned them to one of two groups. The first group was allowed to immediately obtain a medical marijuana card, while the second group had to wait 12 weeks before getting one. Both groups were allowed to choose their cannabis products at a dispensary, with no limits on the dose or frequency of use.

Participants in the immediate card acquisition group reported significantly more cannabis use in the study period, with nearly one in five (17%) developing CUD symptoms such as craving, tolerance and withdrawal within 12 weeks. The odds of having CUD were nearly 3 times higher in the immediate acquisition group than in the delayed acquisition group.

“This trial showed that CUD can develop at a fast rate within the first 12 weeks of medical marijuana card ownership, suggesting that those with a card may develop CUD at a similar rate as those who use cannabis recreationally and that the (medical) motive for use may not be protective,” researchers reported in in JAMA Network Open.

“Although most cases of CUD onset in the trial were mild, with 2 to 4 symptoms, these symptoms developed over a short, 12-week initial exposure. The most commonly reported CUD symptoms were higher tolerance and continued use despite the recurrent physical or psychological problems caused or exacerbated by cannabis.”

People with anxiety or depression -- the most common conditions for which medical cannabis is sought -- were at significantly higher risk of developing CUD than those with pain and insomnia.

Incidence of Cannabis Use Disorder

SOURCE JAMA NETWORK OPEN

“Our study underscores the need for better decision-making about whether to begin to use cannabis for specific medical complaints, particularly mood and anxiety disorders,” said Gilman, who called for more regulation of medical marijuana.  “There needs to be better guidance to patients around a system that currently allows them to choose their own products, decide their own dosing, and often receive no professional follow-up care.”

Cannabis advocates say Gilman’s findings are at odds with larger observational studies (here, here and here) that found cannabis use disorder declined in states that legalized medical marijuana. They feel the study also lacked detail of CUD symptoms or what impact they had.

“Although the authors stress the notion that those in the card-holders groups were more likely to be diagnosed with symptoms of CUD, they never identify what these symptoms were, their severity, or how disruptive they were to these individuals daily lives and functioning — or even if in fact they were at all,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group. 

“Finally, it should be recognized that virtually all therapeutic agents possess varying safety profiles. Medical cannabis is not innocuous. But its safety profile is far superior to that of many conventional pharmaceuticals for which it can provide an alternative, including opioids and benzodiazepines — even if one is to take these findings at face value.” 

A recent survey found that twice as many Americans are now using cannabis or cannabidiol (CBD) to manage chronic pain than opioid medication.

Cognitive Problems Persist in Patients with Long Covid

By Pat Anson, PNN Editor

About 70% of people with long covid have concentration and memory problems several months after their initial infection with Covid-19, according to new research at the University of Cambridge. The severity of the symptoms appears to be linked to the level of fatigue and headache people experienced during their initial illness.

Long covid is a poorly understood disorder characterized by body pain, fatigue, cognitive impairment and difficulty sleeping. About a third of people infected with coronavirus develop symptoms that can last for many months.   

In their study of 181 long covid patients, published in the journal Frontiers in Aging Neuroscience, researchers found that 78% reported difficulty concentrating, 69% had brain fog, 68% experienced forgetfulness, and 60% had trouble finding the right word to use in speech. They also performed poorly in cognitive tests, with significantly lower ability to remember words and pictures.

“This is important evidence that when people say they’re having cognitive difficulties post-COVID, these are not necessarily the result of anxiety or depression. The effects are measurable - something concerning is happening,” said co-author Muzaffer Kaser, PhD, a psychiatrist and researcher at the University of Cambridge. “Memory difficulties can significantly affect people’s daily lives, including the ability to do their jobs properly.”

The findings are further evidence that Covid-19 will have a lasting impact around the world, long after the pandemic subsides. Cambridge researchers say their study supports other findings that suggest society will face a “long tail” of workforce illness due to long covid.

“Long covid has received very little attention politically or medically. It urgently needs to be taken more seriously, and cognitive issues are an important part of this. When politicians talk about ‘Living with COVID’ – that is, unmitigated infection, this is something they ignore. The impact on the working population could be huge,” said senior author Lucy Cheke, PhD, a psychologist and lecturer at Cambridge.

To help understand the cause of the cognitive problems, Cheke and her colleagues investigated other symptoms that might be linked. They found that people who experienced fatigue and neurological symptoms, such as dizziness and headache, during their initial illness were more likely to have cognitive issues later on.

Participants were assigned to carry out multiple tasks to assess their decision-making and memory. These included remembering words on a list, and remembering which two images appeared together. The results revealed a consistent pattern of memory problems in people with long covid -- problems that were more pronounced in those whose initial neurological symptoms were more severe.

“People think that long covid is ‘just’ fatigue or a cough, but cognitive issues are the second most common symptom - and our data suggest this is because there is a significant impact on the ability to remember. There is growing evidence that COVID-19 impacts the brain, and our findings reflect that,” said Cheke.

Study participants were recruited between October 2020 and March 2021, when the Alpha variant and the original form of SARS-CoV-2 were still the dominant forms of the virus.

Very few of the patients had symptoms severe enough to be admitted to a hospital. But even among those who were not hospitalized, researchers found that people with severe initial symptoms were more likely to develop long covid than those with mild symptoms. They also found that people over 30 were more likely to have severe ongoing symptoms than younger ones.

“Infection with the virus that causes COVID-19 can lead to inflammation in the body, and this inflammation can affect behaviour and cognitive performance in ways we still don’t fully understand, but we think are related to an early excessive immune response,” said Kaser.

As is often the case with chronic illness, half of the patients with long covid reported difficulty getting medical providers to take their symptoms seriously, perhaps because cognitive symptoms do not get the same attention as respiratory problems.

The Cambridge study currently has no data on long covid associated with the Delta or Omicron variants of coronavirus, although new patients are being recruited to fill that void. The researchers say more studies are needed to understand the complex effects of Covid on the brain, cognition and mental health.

One way to reduce your risk of long covid is to get vaccinated. A UK study last year found that people who received the Moderna, Pfizer or AstraZeneca vaccines had significantly lower risk of an infection that turns into long covid.

CDC Censoring Public Comments About Revised Opioid Guideline

By Pat Anson, PNN Editor

The U.S. Centers for Disease Control and Prevention has censored over a dozen public comments about its revised opioid guideline to remove negative references to Dr. Roger Chou, one of the guideline’s co-authors.  

Chou is a controversial figure in the pain community. A prolific researcher and an outspoken critic of opioid prescribing, Chou heads the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University.

Over the last five years, the university has received nearly $2 billion in contracts from the CDC and other federal agencies, much of it going to the EPC to support Chou’s research. That research, which generally discourages the use of opioids, is cited over 100 times in the revised CDC guideline.

The CDC published the revised draft in the Federal Register last month and invited the public to submit comments, with the agency cautioning posters that it “may choose to redact, or withhold, submissions containing private or proprietary information.”

Of the 2,600 submissions received so far, over 280 have been edited in some way, mostly to remove personal information about the poster or their medical provider

SOURCE: REGULATIONS.GOV

But at least 15 comments critical of Chou’s research and his role in writing the opioid guideline have also been edited to remove his name, even though much of the information they contain is already public and not proprietary.

Chou’s name is redacted four times from this post by Emma W:

“I think it’s reasonable for them to redact private information, physicians’ names, clinic names, etc. I’m all for protecting privacy. But it makes no sense to me that they would redact the names of guideline authors and/or the authors of research papers they directly cite as evidence,” said Emma, who asked that we not use her last name. “I did not personally make any offensive, rude, or vulgar remarks about him in my comment, so I’m still at a loss as to why I and some others were singled out.”

In addition to being a co-author of the revised guideline, Chou was one of the authors of the original 2016 guideline, which led to significant cutbacks in opioid prescribing nationwide. He also continues to serve on the CDC’s Board of Scientific Counselors, despite admitting to a financial conflict-of-interest (COI) at a board meeting last year.

“Since CDC funds Chou’s research, which supports their guidelines, my guess is that they’re going above and beyond to protect him from criticism,” Emma told PNN. “I suppose I should’ve expected this, considering absolutely nothing has been done about his continuing involvement in these guidelines despite his COIs.”

“It is outrageous but I’m not surprised,” said Julie Killingworth, whose comment was edited 6 times to remove the names of Chou and others.

“I thought my comment would be removed because I stopped appeasing the CDC with politeness long ago. I’m not surprised the CDC is silencing people they have cruelly targeted to be tortured,” Killingworth told PNN. “The CDC does not deserve the national respect they feel entitled to receive.” 

To be clear, not every post that references Chou has been edited. PNN identified 5 posts where his name has not been redacted. Those comments are also critical of Chou’s extensive involvement researching, developing and writing the guideline.

“I am concerned about the legality of redacting public comments. This in my experience is quite irregular,” says Terri Lewis, PhD, who co-authored a 2021 paper that looked into Chou’s conflicts of interest. “It doesn't change what are legitimate concerns about what are very real conflicts of interest and the failure to disclose same, especially in light of other historical facts that are emerging.”

In addition to the Chou redactions, the CDC has censored several comments that mention Dr. Andrew Kolodny by name and other members of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group that Kolodny founded.

Chou has collaborated on several occasions with PROP, including a 2019 op/ed he co-authored 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.”

(3/31/22 Update: Nearly three weeks after we asked CDC why the names of Chou and others are being redacted, we received this reply from a spokesperson:

“Our approach with comments on this FRN (Federal Register Notice) was to redact all individuals’ names to protect privacy. With so many comments, there have been a few that were not redacted in line with this approach, but the intent was to redact names of any and all individuals.”

The spokesperson said the CDC may also “redact or withhold certain submissions” that contain private or proprietary information, inappropriate language, or duplicated public comments that could indicate a mass-mail campaign.)

The CDC will continue to accept public comments about the revised guideline until April 11. Click here to make one.

Ironically, the revised guideline has generally been received favorably by the pain community because it gives doctors more flexibility in prescribing opioids. Some patients and advocates are leery, however, that the revisions won’t restore access to opioid medication or fix all the other problems the original guideline created, such as patients being forcibly tapered or reduced to ineffective doses.

How the Epstein Barr Virus Causes Arachnoiditis

By Dr. Forest Tennant, PNN Columnist

The Epstein-Barr Virus (EBV) has long been known to cause autoimmune complications. For example, I described infectious mononucleosis in kidneys (glomerulonephritis) associated with EBV back in 1969, some 53 years ago.

Recently EBV has been shown to cause multiple sclerosis (MS), as well as certain cancers. Our studies have also revealed that many, if not the majority, of persons with adhesive arachnoiditis (AA) have extremely high EBV antibody levels. We now believe that EBV can cause AA as well as MS. 

Anything that boosts or helps a disorder to develop, is called a “co-factor.” In the case of EBV and AA, the “co-factors” or “co-partners” may include Ehlers-Danlos Syndromes, autoimmune diseases such as psoriasis, Lyme disease, and some other viruses like cytomegalus, coxsackie and covid.

‘Collagen Eaters’

Although almost everyone gets infected with EBV during their lifetime, some persons develop a large number of EBV antigens that literally attack and “eat away” or otherwise cause collagen to deteriorate and weaken. If the body creates large numbers of antigens, large numbers of antibodies are simultaneously made to hopefully counter them.

EBV collagen eating antigens like to attack tissues around the spine that have a lot of collagen. This includes intervertebral discs, cauda equina nerve roots, and the arachnoid-dural covering of the spinal canal. If collagen is weak or absent in spinal tissues, discs may slip, inflammation may form, and fluid leaks and cysts may develop.

Get Tested for EBV

All persons with confirmed or suspected AA should be tested for EBV antibodies.

Laboratories today do three types of tests for EBV. One is to tell if you currently have an active infection and the other two measure antibody levels to determine if you have had EBV in the past. If your antibodies are considerably above normal range, it suggests you have collagen eating antigens that put you at risk of developing AA.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from a bulletin recently issued by the Arachnoiditis Research and Education Project. Readers interested in subscribing to the bulletins should click here.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

State Laws Had Little Impact on Opioid Prescribing

By Pat Anson, PNN Editor

When the CDC’s opioid prescribing guideline was released in 2016, dozens of states began efforts to codify the guideline’s “voluntary” recommendations into laws and regulations. To date, according to The Pew Charitable Trust, 40 states limit the dose or initial supply of opioid medication, and all 50 states have implemented prescription drug monitoring programs (PDMPs) to track opioid prescriptions and the doctors who write them.

On the surface, it may appear the state policies are working, because opioid prescribing in the U.S. has plunged over 40 percent, to levels not seen in 20 years. But a large new study found that state laws regulating opioids have had very little effect on prescribing – suggesting that other factors may be at work making doctors reluctant to prescribe opioids.

Researchers at Johns Hopkins Bloomberg School of Public Health studied commercial insurance claims for nearly 7.7 million adults in 13 “treatment states” that limited prescribing, established PDMPs or targeted pill mills. The analysis included data for nearly 2 million patients diagnosed with arthritis, low back pain, headache, fiibromyalgia or neuropathic pain.

The study findings, published in Annals of Internal Medicine, show that prescribing and PDMP laws in treatment states were associated with an average change of less than 1% in the proportion of patients receiving an opioid prescription.

For example, in Idaho an estimated 9.18% of pain patients received an opioid prescription prior to the state passing a mandatory PDMP law that required doctors to look up a patient’s prescription drug history. In the first two years of the law’s implementation, that percentage fell only slightly to 9.03% of patients.

State laws have also had a negligible impact on dose and supply. Patients who received an opioid prescription in treatment states had an average change of less than one day in the supply of opioids and an average dosage change of less than 4 morphine milligram equivalents (MME) per day.

“We did not find an association between state opioid prescribing laws and receipt of opioid prescriptions or guideline-concordant nonopioid pain treatments among commercially insured adults. Across the 13 states that implemented laws, the change in treatment attributable to the law was consistently small in magnitude and not
statistically significant,” researchers reported.

“The findings suggest that the decreasing volume of opioid prescribing in the United States may be driven more by shifting clinical guidelines, professional norms, or other factors than by these laws.”

PNN asked lead author Beth McGinty, PhD, if the “other factors” that caused opioid prescribing to decline were the CDC guideline itself or the chilling effect many doctors felt from expanded investigations by state medical boards, law enforcement and the Drug Enforcement Administration.

“Our study was not designed to identify those other factors, so I can’t say for sure what has driven these declines.  Overall declines could be due to changing clinical practices nationwide in response to the CDC guidelines or many others,” McGinty replied in an email.

“Declines could also be driven by a range of other efforts to curb opioid prescribing, perhaps the DEA investigations you mention but also other efforts like health system interventions to reduce prescribing. As I said above, our study was designed to evaluate just the state laws, not these other factors, so I can’t say for sure."

“It's really hard to tell exactly what the findings here mean, despite a valiant effort on the part of the researchers,” says Bob Twillman, PhD, former Executive Director of the Academy of Integrative Pain Management.

Twillman says the CDC guideline was “weaponized” in so many ways by regulators, insurers and states that it’s difficult to measure the impact of any single policy or regulation. It was the cumulative impact of them all that drove down opioid prescribing.

“In truth, the most that you can conclude from this study is that these laws did not appear to reduce prescribing. Unfortunately, in the context of an avalanche of other policies, that conclusion doesn't paint a very accurate picture of what is happening to patients because of all the policies,” Twillman told PNN.

State Laws Failed to Reduce Overdoses

McGinty’s study is not the first to find that PDMPs have been largely ineffective – and may even be making the opioid crisis worse. A 2021 study by the Reason Foundation found that overdoses from illicit fentanyl and heroin increased in states after PDMP’s were adopted. A 2018 study by researchers at Columbia University and University of California, Davis had similar findings. 

State laws that limit the dose and quantity of prescription opioids have also failed to stop overdoses from increasing.

In 2016, Massachusetts became the first state in the nation to limit the initial supply of opioid prescriptions to 7 days. The law has had little impact on overdoses. Over 2,000 people still die annually from opioid overdoses in Massachusetts, a rate that has remained steady. The most recent data shows that illicit fentanyl was involved in 92 percent of overdose deaths in the state.

It was the 2016 CDC guideline that encouraged Massachusetts and many other states to adopt limits on initial opioid prescriptions. For short-term acute pain, the guideline said that opioids for “three days or less will often be sufficient; more than seven days will rarely be needed.”

A newly revised draft guideline drops any reference to the number of days and gives physicians more latitude, recommending that opioids be prescribed for acute pain “for no longer than the expected duration of pain severe enough to require opioids.”

More Than Just CDC Opioid Guideline Needs Changing

By Roger Chriss, PNN Columnist

The CDC’s draft revisions to its 2016 opioid guideline are generally seen as an improvement by pain management experts because they give doctors more flexibility to prescribe opioids. But how much will prescribing really change?

Forty states have enacted laws that limit the supply or dose of opioid prescriptions, according to the Pew Charitable Trust. Some states may resist making changes.

“For the eased guidelines to have their intended effect, states would need to amend or repeal existing statutes that limit opioid prescriptions to three to seven days and set ceilings on the daily dose doctors can prescribe,” Stateline reported.

The reasons are simple. Amid a deteriorating drug overdose crisis and a complex prescribing landscape, the proposed changes in the CDC guideline are likely to be seen at the state level as a negative for public health. There’s a tangled mess of different opioid regulations that vary from state to state.

“Relaxing those regulations now would wreak havoc on states. They won’t know what to do,” says Gary Franklin, MD, who is Vice-President of State Regulatory Affairs for Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

“We’ve made quite a dent in prescription painkiller use,” Franklin told EMS1. “But we’ve still got a lot of work to do.”

Lewis Nelson, MD, Chair of Emergency Medicine at Rutgers New Jersey Medical School, is concerned about plans to drop the guideline’s recommended dose limit of 90 morphine milligram equivalents (MME) per day. Nelson says the CDC’s “watered down recommendations” will lead to more addiction and overdoses.

“By removing this recommended cap … prescribers may feel it is appropriate to prescribe longer initial prescriptions to their patients,” Nelson told The Daily Targum, a student newspaper at Rutgers. “This is one of the key factors that created the opioid crisis in the early 1990s that lasted through today.”  

Nelson and Franklin were both key advisors to the CDC during the drafting of its 2016 guideline, serving on a panel known as the “Core Expert Group.” They did not have a similar role in the drafting of the revised guideline.

Federal Agencies and States Do Their Own Thing

Because they are controlled substances, prescription opioids are not regulated the same way as other medications. Manufacturing levels are determined by the DEA, which annually determines production quotas for opioids based on input from the FDA, CDC, Centers for Medicare and Medicaid Services (CMS), and individual states. The DEA has been steadily reducing production quotas for prescription opioids for almost a decade and seems unlikely to change course anytime soon.

Drug approval falls to the FDA, which says one of its “highest priorities” is reducing the number of Americans addicted to opioids. “This may be achieved by ensuring that only appropriately indicated patients are prescribed opioids and that the prescriptions are for durations and doses that properly match the clinical reason for which the drug is being prescribed in the first place,” the FDA says on its website.

Federal programs like Medicare, Medicaid and VA/Tricare, as well as private insurers and pharmacies, exert considerable influence on clinical practice via formularies, guidelines, and prior authorizations.

States ignore the CDC, FDA and other federal regulations when it suits their ends, as seen with Florida’s new “Buck the CDC” effort against federal mask mandates and covid guidelines.

States also set their own regulations for legalizing cannabis or decriminalizing hallucinogens.

When it comes to healthcare and public health, each state does its own thing, even if they conflict with federal policy and are detrimental to other states.

Patient advocate Richard “Red” Lawhern deftly summarizes the many nuances of the CDC’s draft guidance with “the devil is in the details.”  And the National Pain Advocacy Center has a detailed analysis of the draft, with suggestions for further advocacy.

The CDC has been a convenient scapegoat for the rapid opioid tapering, patient abandonment, and even suicides that have occurred in recent years. But the reality of regulating prescription opioids and treating chronic pain is complex. Even if CDC does finalize the proposed changes in its draft guideline, there is still a long way to go to restore some semblance of order and stability in pain management.

The CDC is one part of a much larger system that probably needs to change as much as the 2016 guideline need to be updated.

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.