How Should the CDC Opioid Guideline Be Changed?

By Pat Anson, PNN Editor

It was five years ago today – March 15, 2016 – that the Centers for Disease Control and Prevention released its controversial opioid guideline, which discourages doctors from prescribing opioids for chronic pain.   

“This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death,” the CDC said.

Although voluntary and only intended for primary care physicians, the guideline soon became the “standard of care” in the United States, with many states, doctors, insurers, pharmacies and regulators adopting its recommendations, such as limiting opioid doses to no more than 90 morphine milligram equivalents (MME) per day.

Soon after the guideline was released, the CDC was warned by its own consulting company that “some doctors are following these guidelines as strict law rather than recommendation, and these physicians have completely stopped prescribing opioids.” Over three hundred healthcare professionals also warned that forced opioid tapering was causing “an alarming increase in reports of patient suffering and suicides.”

A PNN survey two years ago found that over 85 percent of patients believed the CDC guideline made their pain and quality of life worse, significantly reduced their access to pain care, and drove some to alcohol and illegal drugs for pain relief.

Not until 2019, however, did then CDC Director Robert Redfield acknowledge the guideline was causing problems and pledged to “clarify its recommendations to help reduce unintended harms.”

Two years later, the CDC is still in the process of revising and possibly expanding the guideline, with the goal of releasing an update for public comment late this year.

Should the guideline be changed? Has it been successful in improving pain treatment? Did it reduce addiction, overdose and death?

We thought this would be a good time to conduct another survey of patients and healthcare providers, to see what changes they’d recommend to the CDC and the “Opioid Workgroup,” a panel of experts that is advising the agency.

Among the questions we’re asking is whether the recommended dose limit of 90 MME/day should be scrapped; if the guideline should be expanded to include treatment of short-term acute pain; and whether the CDC should give advice on treating specific conditions, such as low back pain or fibromyalgia.

Click here to take the survey. It should only take a few minutes to complete. Your identity and any personal health information will be kept confidential.

Covid Long-Haulers Face New Battle for Disability Benefits

By David Tuller, Kaiser Health News

Rickie Andersen took a brief break from work last March after she fell ill. Her cough, fever and chills were typical covid-19 symptoms, but coronavirus tests were so scarce she could not obtain one to confirm the diagnosis.

After Andersen returned to her job as an information systems project manager in the San Francisco Bay Area, she struggled with profound fatigue, cognitive difficulties and other disabling complaints. For six months, she tried to keep awake during meetings and finish basic tasks that took much longer than before.

Finally, she decided to retain legal help so she could take advantage of the disability insurance coverage offered as an employee benefit. “I realized this is not going to be a short-term thing,” Andersen said.

Hundreds of thousands of people around the world are experiencing what is being called “long covid” — a pattern of prolonged symptoms following an acute bout of the disease. Many have managed to continue working through accommodations like telecommuting, cutting down on hours and delegating responsibilities.

Others have found it impossible to fulfill their professional obligations and are making the tough decision to stop working and seek disability benefits. But as they pursue the application process, they are discovering a particular set of challenges.

Given the lack of testing in the first months, many “long haulers,” like Andersen, have no laboratory proof of infection. While antibody tests can provide such evidence, their accuracy varies. Moreover, many of the reported symptoms, including fatigue and cognitive impairment, are subjective and not clearly linked to specific organ damage.

Beyond that, compiling a thorough record for a disability application and navigating the bureaucratic hurdles require sustained brain power, something many long-haul patients can no longer muster.

Barbara Comerford, a New Jersey disability lawyer, said she received dozens of inquiries starting last fall from long haulers seeking advice on filing for disability and often citing what is being called “brain fog” as their main complaint.

“Most are people calling to say, ‘I thought I could do it. I can’t. My mind doesn’t function for more than really brief periods of time,’” Comerford said.

In the U.S., close to 30 million people have tested positive for the coronavirus, although many cases of infection are asymptomatic. What proportion might be affected by long-term illness isn’t known. Scientific understanding of the phenomenon is in its infancy.

In January, The Lancet reported that around three-quarters of more than 1,700 covid patients who had been hospitalized in Wuhan, China, reported at least one ongoing symptom six months later. More recently, investigators from the University of Washington reported in JAMA Network Open that around 30% of 177 patients who had tested positive for the coronavirus still reported symptoms when they were surveyed one to 10 months later.

Strict Criteria for Benefits

The Social Security Administration provides long-term disability to American workers who qualify under its strict criteria, but applicants often get turned down on the first try. A few states, including California and New York, provide short-term disability benefits, in some cases for up to a year.

Tens of millions of Americans also have private disability coverage, most often as part of their employment benefit packages.

The maximum currently available to an individual through the Social Security Disability Insurance program is just over $3,000 a month. A typical private long-term disability plan might cover 60% of a beneficiary’s base salary, with a much higher maximum amount.

Sandy Lewis, a pharmaceutical industry researcher, fell ill last March with what she assumed was covid. She recovered but relapsed in April and again in May.

Through her employer-based insurance coverage, she received short-term disability for November and December, but the insurer, Prudential Financial, rejected her request for an extension. Soon after, she was diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS, a debilitating illness that can be triggered by viral infections.

Lewis, who lives outside Philadelphia, is planning to appeal Prudential’s rejection of the short-term extension and apply for long-term disability. But the matter is unlikely to be resolved before fall. The situation has left her feeling “devastated,” she said, and in serious financial distress.

“This has been such an arduous journey,” she said. “I have no income and I’m sick, and I’m continuing to need medical care. I am now in a position, at 49 years old, that I may have to sell my home during a pandemic and move in with family to stay afloat.”

In Lewis’ case, a Prudential reviewer noted that her symptoms were “subjective” and that there were “no physical exam findings to correlate with any ongoing functional limitations,” according to Cassie Springer Ayeni, an Oakland disability lawyer who is representing her as well as Andersen.

Prudential would not comment on a specific case. Evan Scarponi, chief claims officer, said in a statement that “our collective understanding of covid-19 and any associated long-term effects are still evolving” but that Prudential is “well-versed in evaluating both subjective and objective aspects of disability claims.”

Lawyers and advocates in the field expect the numbers of covid-related long-term disability applicants to rise this year. But it’s still too soon to detect any such increase, said a spokesperson for the American Council of Life Insurers, a trade association. Workers typically must be unable to work for half a year before becoming eligible for long-term disability benefits, and applying can itself be a lengthy process.

‘No Objective Evidence’

Brian Vastag, a former Washington Post science and health reporter with ME/CFS, stopped working in 2014 and then sued Prudential after it rejected his long-term disability claim. Insurance companies, he said, can easily find reasons to dismiss applications from claimants with chronic illnesses characterized by symptoms like fatigue and cognitive impairment.

“The insurance companies will often say, ‘There’s no objective evidence, so we have nothing to support your claim,’” said Vastag, who won his case against Prudential in 2018. “I’m worried about the long-covid patients who can’t work anymore.”

Claimants can appeal a rejection. If the insurer rejects the appeal, claimants have the right to sue, as Vastag did. However, most such cases fall under the Employee Retirement Income Security Act of 1974. Because this federal law requires a losing insurer to pay the unpaid claims but does not provide for punitive or compensatory damages, critics argue it incentivizes the denial of coverage.

In the event of litigation, the court’s role is to assess the already existing evidentiary record. That means it is essential to present a robust case in the initial application or during the administrative appeal before any litigation begins, said Ayeni, the disability lawyer for Andersen and Lewis.

“It’s the only shot to build a record for the courts, to develop a full body of evidence,” she said.

However, a successful disability case ultimately depends on documenting inability to work, not on obtaining a specific diagnosis. To augment the medical evidence, Ayeni often sends clients for neuropsychological testing, investigations of lung function and other specialist assessments. She also gathers affidavits from family members, professional colleagues and friends to confirm patients’ accounts.

In Rickie Andersen’s case, the strategy worked. Recognizing how complicated the application process was likely to be, she sought legal help early on. The insurer contracted by her employer approved her for short-term benefits late last year and granted her application for long-term benefits in February.

“I knew all of it was completely exhausting, so it wasn’t something I thought I could do on my own,” Andersen said.

This story was produced by Kaiser Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation.

New Advocacy Group Seeks Smarter Solutions to Pain Crisis

By Pat Anson, PNN Editor

If you’re like me, you are puzzled at times by the sheer number of patient advocacy groups working on behalf of pain sufferers. There are dozens and they all have the same goals: improve the quality of pain care and give patients a voice in a society that seems to have turned its back on them.  

Most of these groups are primarily run by one or two people, have little to no funding, no board of directors, no mission statement and no website. What they lack in money and organization, they make up for in passion and personality driven posts on Facebook, Twitter and other social media, sometimes attracting thousands of followers.

But all too often, the online discourse turns into endless bickering between advocates that accomplishes little for the pain community. Tired of the infighting, some advocates stop advocating and drift away.

A new patient advocacy group was launched this week that is trying to change that. The National Pain Advocacy Center (NPAC) is a 501(c)(3) non-profit led by Kate Nicholson, a pain sufferer and civil rights attorney, who emerged as a patient advocate in 2017 with an inspirational TedTalk that explained how opioids helped her walk again after a botched surgery.  

KATE NICHOLSON

Nicholson has been working publicly – and quietly behind the scenes -- ever since, meeting with legislators, healthcare providers, academics, civil rights advocates, and people with pain. NPAC is an outgrowth of the many connections she has made.

“There are people I have worked with over the last few years on select projects. And I think we all felt we had sort of reached our capacity to work as individual actors. We needed to make a change and come together,” Nicholson explained.

“We needed to advocate more broadly for better treatment for pain. Because even though we were able to stop a bad policy here or there, it was a little like whack-a-mole. They just keep coming back. We needed a broader reach.”

NPAC has a large and diverse group of volunteers on its board of directors and advisory councils; including some familiar names in patient advocacy, such as Laura Mills, Leo Beletsky, Stefan Kertesz, Sally Satel, Anne Fuqua, Jennifer Oliva, Chris Freeman and Sean Mackey, to name just a few.

The advisory councils are so inclusive they include several people who have struggled with substance abuse or work in addiction treatment – which might get some push back from others in the pain community. Nicholson says both pain and addiction need to be addressed if NPAC is to be seen as a credible organization.

“Anytime you meet with policy makers, these two issues have become intertwined in the public conversation because of the way the story about opioids has been told,” she told PNN. “I’m not one of those people who think that no one got hurt because of liberal prescribing. There are people who are susceptible to addiction. I see it as two very stigmatized groups who need to band together to some extent because right now the infighting is causing everyone to go down, really.”

NPAC has gotten some grant money from the Open Society Foundation, another association likely to be questioned because it is funded by liberal philanthropist George Soros, a billionaire who is a magnet for right-wing conspiracy theories.

Nicholson has pledged to never to accept funding from pharmaceutical companies or other organizations that may create a conflict of interest – real or imagined -- with NPAC’s mission.

“Our goal is to change minds and shift policies,” says Nicholson, who serves on a panel advising the CDC as it makes revisions to its controversial 2016 opioid guideline. She says the current state of research and understanding of pain is in “the Dark Ages.”

“My own feeling is that pain needs rebranding. If we really think chronic pain is a disease, then shouldn’t we be calling it something different? We don’t call depression ‘chronic sadness’ even though everybody feels sad,” Nicholson said. “I really feel like there needs to be a shift in how we talk about pain and how we understand it. There really needs to be a much bigger conversation than just one treatment modality.”

Experimental Gene Therapy May Relieve Chronic Pain

By Pat Anson, PNN Editor

A new study by researchers at the University of California San Diego suggests that gene therapy could someday be used to treat a variety of chronic pain conditions without the use of drugs.

In experiments on laboratory mice, researchers found that temporarily repressing a gene involved in sensing pain increases pain tolerance, lowers pain sensitivity and provided months of pain relief without causing numbness. Their findings were published in the journal Science Translational Medicine.

“What we have right now does not work,” said first author Ana Moreno, PhD, CEO of Navega Therapeutics, which is developing gene therapies to treat chronic pain. “There’s a desperate need for a treatment that’s effective, long-lasting and non-addictive.”

Moreno was grad student at UC San Diego studying gene repression when she came across a paper about a genetic mutation that causes humans to feel no pain. The mutation blocks a protein -- called NaV1.7 -- that’s involved in transmitting pain signals in the spinal cord.

That’s when she came up with the idea of suppressing the gene using the CRISPR gene editing tool. Moreno was working with a version of CRISPR that uses what’s called “dead” Cas9, which lacks the ability to permanently cut DNA. Instead, it sticks to a gene and temporarily blocks its expression.

“By targeting this gene, we could alter the pain phenotype,” Moreno explained. “It’s not cutting out any genes, so there are no permanent changes to the genome. You wouldn’t want to permanently lose the ability to feel pain.

“One of the biggest concerns with CRISPR gene editing is off-target effects. Once you cut DNA, that’s it. You can’t go back. With dead Cas9, we’re not doing something irreversible.”

Moreno and UC San Diego bioengineering professor Prashant Mali, PhD, co-founded Navega Therapeutics to work on developing gene therapy as a treatment for pain.  They teamed up with Tony Yaksh, PhD, a professor of anesthesiology and pharmacology at UC San Diego School of Medicine, and developed a CRISPR/dead Cas9 system to target and repress the gene that codes for NaV1.7.

When they administered spinal injections of the system into laboratory mice with inflammatory and chemotherapy-induced pain, the mice displayed higher pain thresholds than mice that did not receive the gene therapy. The treated mice were slower to withdraw a paw from painful stimuli (heat, cold or pressure) and spent less time licking or shaking their paws after being hurt.

The treatment was still effective after 44 weeks in the mice with inflammatory pain and 15 weeks in those with chemotherapy pain. The treated mice did not lose sensitivity or display any changes in normal motor function.

To validate their results, the researchers performed the same tests using another gene editing tool called zinc finger proteins. It’s an older technique than CRISPR, but works the same way. Spinal injections of the zinc fingers into mice produced the same results as the CRISPR-dead Cas9 system.

“We were excited that both approaches worked,” Mali said. “The beauty about zinc finger proteins is that they are built on the scaffold of a human protein. The CRISPR system is a foreign protein that comes from bacteria, so it could cause an immune response. That’s why we explored zinc fingers as well, so we have an option that might be more translatable to the clinic.”

The researchers say this solution could work for a variety of chronic pain conditions, including diabetic neuropathy, sciatica, and chemotherapy pain. They believe their gene therapy platform could also be used to treat short-term acute pain.

“Think of the young athlete or wounded war fighter in which the pain may resolve with wound healing,” Mali explained. “We would not want to permanently remove the ability to sense pain in these people, especially if they have a long-life expectancy. This CRISPR/dead Cas9 approach offers this population an alternative therapeutic intervention—that’s a major step in the field of pain management.”  

Researchers at UC San Diego and Navega are planning further studies of pain-relieving gene therapy on non-human primates. Their goal is to begin human clinical trials in a couple years. Their work is funded by UC San Diego Institutional Funds and the National Institutes of Health.

A Tough Pill to Swallow

By Mia Maysack, PNN Columnist

Nothing will change if we don't demand it. So many of us are exhausted, fed up, disheartened and tempted to call it quits. But our lives are worth fighting for, as is the quality of them. 

I have a loved one who was prescribed multiple different medications for years to aid with pain, anxiety, depression and sleep disturbance. Though these medicines were taken as directed, they altered this person's brain chemistry and cultivated a physical dependence -- which isn't something that was ever mentioned to them by a medical professional as a possibility or concern. 

No longer willing to compromise with the adverse side effects, they began researching how to appropriately and safely wean themselves off these pills -- only to find out that many others who tried to were either unable to quit or lost their lives attempting to do so. 

Although it was never recommended or suggested, my loved one chose to stop cold turkey overnight, a decision they almost didn't make it through. But their determination to reclaim a normal existence exceeded the potential dangers. 

This left me with major concerns. Why were these capsules doled out for such a long period of time without a mention, thought, discussion or intervention of other therapies?  Generally, our bodies are not built or equipped to internalize anything foreign for so long, let alone forever.

What is my loved one to do now? Where could they turn? And who was going to help them?

It shouldn't be a newsflash that there's an on-going war against patients, specifically in relation to untreated pain and/or opioid use. But there are some things not everyone may realize, such as the major differences between the abuse of prescriptions, addiction and following provider instructions. Yet all three have ignorantly been grouped together.

To add further insult to injury, it's those who cannot begin relating to any of these circumstances who usually have the opinions and power to manage them. That’s similar to how I, as a white woman, cannot begin to fully understand the experiences of other ethnicities.

The same principle applies to someone who has never encountered intractable, unbearable, relentless and agonizing discomfort. It makes no sense as to how it is justified. The lack of firsthand knowledge disqualifies anyone to judge or make decisions on behalf of others directly impacted by something they cannot begin to relate to. It also boils down to a severe lack of humility.

All it would require is a shift in circumstance -- a fall, accident, surgery or unexpected diagnosis for a sudden complete change in stance on these matters.

When deaths are reported, they are often categorized under one “cause.” And when it is discovered that an individual who passed away was taking opioids, that is the box that usually gets checked. That not only unfairly minimizes respect for those we've lost, but also skews the data, painting an improper and inaccurate statistical picture to further victimize some of our most vulnerable.  

Instead of being given options and solutions, people who should be protected and served by the medical system have been and continue to be punished, while also neglected and their voices ignored.    

Fighting amongst each other by comparing our individual situations is not an adequate use of our energy. That same effort and passion would be better devoted toward contacting legislators and institutions falsely producing this hysteria, to express our dissatisfaction, demand acknowledgement and to create forward momentum in making things better.   

It isn’t acceptable to go from one extreme to another while not solving anything. This alters what the problem is, as opposed to offering an actual fix. How is it justified that the World Health Organization calls management of pain a “fundamental human right,” while millions are not only suffering but suicide rates are at an all-time high due to medical abandonment?   

Politics do not belong in the realm of healthcare. But when our integrity as “The People” is being compromised, this becomes an issue that impacts each and every one of us. If we do not fight for our virtues, we’ll lose our liberty.               

Mia Maysack lives with chronic migraine, cluster headaches and fibromyalgia. Mia is the founder of Keepin’ Our Heads Up, a Facebook advocacy and support group, and Peace & Love, a wellness and life coaching practice for the chronically ill.

Low Dose Naltrexone Emerging as Treatment for Intractable Pain

By Forest Tennant, PNN Columnist

A major advance in pain management is the discovery of low-dose naltrexone (LDN), a non-opioid medication used to treat substance abuse. When prescribed off-label, LDN not only relieves pain, but has anti-inflammatory and immune boosting properties on brain and spinal cord tissues. It is now the preferred, first drug of choice for people living with constant, intractable pain.

Only those persons who are not currently on daily opioids should take LDN. A major purpose of LDN is to prevent the necessity of daily opioids, including buprenorphine/Suboxone.

A starting dosage of LDN is usually 0.5 – 1.0 milligrams taken twice a day. The average maintenance dose is about 3 – 5mg given twice a day. The maximum dose is about 7mg taken twice a day.

LDN should ideally be a part of a multi-drug program. A nerve conduction blocker (neuropathic) agent such as gabapentin or diazepam will almost always boost pain relief. A dopamine surrogate such as Adderall, Ritalin or mucuna, is also very helpful.  Routinely recommended are standard anti-inflammatory (e.g., Ketorolac) and tissue healing anabolic agents (e.g., DHEA).

A pain flare medication should also be handy and ready. Some patients taking LDN can occasionally take a low dose of tramadol, codeine or hydrocodone for pain flares. Other flare medications include ketamine, CBD, medical marijuana, ibuprofen (800mg), oxytocin, kratom and ketorolac.

Caution and Warning

Persons who currently take daily opioids must withdraw from opioids before starting LDN. In our studies, patients sometimes became deathly ill if they took LDN while still on opioids. Severe withdrawal may set in, pain relief will diminish and, at worst, a cardiac-adrenal crisis may be precipitated.

If one has Intractable Pain Syndrome and is currently on a regimen including opioids that satisfactorily reduces pain, there is no medical reason to switch to LDN.

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.  

VALUE Study Seeks Patient Perspective on Long-Term Opioid Use

By Pat Anson, PNN Editor

In 2011, the Institute of Medicine released its landmark report, “Relieving Pain in America,” an ambitious project aimed at improving pain care, education and research in United States.

One of the report’s co-authors was Stanford University’s Dr. Sean Mackey, who remembers telling colleagues at the time that more research was needed on the long-term use of opioid pain relievers.     

“One of the questions I put forward to the group was, ‘One of the biggest questions that we need to answer is do opioids help relieve chronic pain for some people?’ Do they actually work? And if so, for whom do they work?” Mackey recalls.

“And surprisingly, ten years later, here we are in 2021 and I would submit to you that we still don’t know the answer to that question. We still do not know how well long-term prescribing of opioids work for chronic pain and for which person they work for. We understand much better who they don’t work for. But we don’t know the flip side.”

Mackey is now leading a study aimed at finally answering the question. The VALUE study is designed to give patients a voice in determining whether opioids can be a safe, effective and long-term treatment for chronic pain.

Mackey and co-investigator Beth Darnall, PhD, along with a team of patient advocates, hope to get up to 500 chronic pain sufferers to enroll in their year-long study. Patients will be asked to participate in three online surveys and three phone calls, answering questions about their pain, symptoms, mood, sleep, quality of life, and whether they encountered any problems or stigma from using opioids.

Long-Term Studies Lacking

Many doctors, regulators and opioid critics claim – disingenuously – that there is no evidence supporting the long-term use of opioids. But the truth is the same could be said for all pain relievers, including non-opioids. Few placebo-controlled studies have been conducted on the long-term use of any pain medication -- simply because it would be unethical to subject a participant to untreated pain for a lengthy period.

That leaves it to patients to share their own experiences with opioids, and a shrinking pool of doctors like Mackey who are not afraid to prescribe them.

“In my caring for people who suffer from pain and for whom it takes a big toll, I have clearly seen a subset of people for whom they do work,” Mackey told PNN. “What we’re trying to do here is transcend what has become a one-size-fits-all approach to patient treatment and the issue of opioids. We’ve become rather guideline-based and we treat all people as if they were an average in a clinical trial. I don’t treat averages. I treat people.

“Everybody is unique and deserves to be treated as an individual. That doesn’t mean that we can’t be guided by those research studies and averages, but we need to get at a more personalized approach. We need to recognize, at least in many of our experiences, there are sub-groups of people who respond to opioids. The problem is we don’t have good data on who they are.”

People who volunteer for the VALUE study should be prepared to spend a fair amount of time answering questions. Each survey will take about 45 minutes to complete. Participants will complete the first survey when they enroll, the second one after 6 months, and the third survey after one year. For each completed survey, patients will be compensated with an Amazon or gift card.

All information collected will be confidential, and won’t be shared with doctors, regulators or insurers. Participants can even use a pseudonym if they don’t feel comfortable using their real names. The VALUE study website has a list of other frequently asked questions.

People interested in participating should contact study coordinator Hannah Cunningham by email at hcunning@stanford.edu or by calling 1-833-668-0277.

“We believe our findings will have broad policy indications at local, state and national levels that will hopefully make opioid prescribing guidelines more patient centered, more effective and safer,” says Mackey.

Study Finds Placebos Disrupt Pain Signals in Brain

By Pat Anson, PNN Editor

Much of the pain relief that a person gets from taking an analgesic medication is due to individual mindset, not the drug itself, according to new research that looks at how the human brain responds to a placebo.

The placebo effect is a well-documented but poorly understood condition in which a patient responds to a drug or treatment that is designed to have no therapeutic value. A 2018 study, for example, found that about half of patients who took a sugar pill they thought was an analgesic had a 30% reduction in pain – a level considered effective for an actual painkiller.    

To better understand how that is possible, researchers at Dartmouth University conducted a meta-analysis of 20 neuroimaging studies involving 603 healthy people who participated in placebo studies. Their findings, recently published in Nature Communications, showed that placebo treatments reduced pain-related activity in multiple areas of the brain.

"Our findings demonstrate that the participants who showed the most pain reduction with the placebo also showed the largest reductions in brain areas associated with pain construction," explains co-author Tor Wager, PhD, a Neuroscience Professor who is principal investigator of the Cognitive and Affective Neuroscience Lab at Dartmouth.

"We are still learning how the brain constructs pain experiences, but we know it's a mix of brain areas that process input from the body and those involved in motivation and decision-making. Placebo treatment reduced activity in areas involved in early pain signaling from the body, as well as motivational circuits not tied specifically to pain."

By examining brain images, researchers were able to identify the placebo effect in regions of the brain that process pain signals (nociception) and generate pain sensations.

They found that placebos strongly affect the thalamus, which processes sights, sounds and other types of sensory input; as well as the basal ganglia, which is important for motivation and pain-related activities.

Placebo treatments also reduced activity in the brain’s posterior insula, which is one of the areas involved in creating pain sensations. This suggests that placebos change the pathway for how pain is processed in the brain. 

"The placebo can affect what you do with the pain and how it motivates you, which could be a larger part of what's happening here," says Wager. "It's changing the circuitry that's important for motivation."

Previous research has found that placebos activate the brain’s prefrontal cortex, which triggers the release of natural, pain-relieving hormones that can block pain signals from being processed.

Researchers say placebo effects likely involve a combination of different brain reactions, depending on the placebo and people's predispositions. In other words, there is no uniformity in the placebo response because everyone is different.

"Our results suggest that placebo effects are not restricted solely to either sensory/nociceptive or cognitive/affective processes, but likely involves a combination of mechanisms that may differ depending on the placebo paradigm and other individual factors," said co-author Ulrike Bingel, PhD, a professor at the Center for Translational Neuro- and Behavioral Sciences at University Hospital Essen.

A 2016 study that looked at brain images of osteoarthritis patients found that about half had mid-frontal brain regions that had more connectivity with other parts of the brain, making them more likely to respond to the placebo effect. That could help could explain why some respond well to pain medication, while others do not.

How Long Haul Covid Alters the Immune System

By Liz Szabo, Kaiser Health News

There’s a reason soldiers go through basic training before heading into combat: Without careful instruction, green recruits armed with powerful weapons could be as dangerous to one another as to the enemy.

The immune system works much the same way. Immune cells, which protect the body from infections, need to be “educated” to recognize bad guys — and to hold their fire around civilians.

In some Covid-19 patients, this education may be cut short. Scientists say unprepared immune cells appear to be responding to the coronavirus with a devastating release of chemicals, inflicting damage that may endure long after the threat has been eliminated.

“If you have a brand-new virus and the virus is winning, the immune system may go into an ‘all hands on deck’ response,” said Dr. Nina Luning Prak, co-author of a January study on Covid and the immune system. “Things that are normally kept in close check are relaxed. The body may say, ‘Who cares? Give me all you’ve got.’”

While all viruses find ways to evade the body’s defenses, a growing field of research suggests that the coronavirus unhinges the immune system more profoundly than previously realized.

Some Covid survivors have developed serious autoimmune diseases, which occur when an overactive immune system attacks the patient, rather than the virus. Doctors in Italy first noticed a pattern in March 2020, when several Covid patients developed Guillain-Barré syndrome, in which the immune systems attacks nerves throughout the body, causing muscle weakness or paralysis.

As the pandemic has surged around the world, doctors have diagnosed patients with rare, immune-related bleeding disorders. Other patients have developed the opposite problem, suffering blood clots that can lead to stroke.

All these conditions can be triggered by “autoantibodies” — rogue antibodies that target the patient’s own proteins and cells. In a report published in October, researchers even labeled the coronavirus “the autoimmune virus.”

Although doctors are researching ways to overcome immune disorders in Covid patients, new treatments will take time to develop. Scientists are still trying to understand why some immune cells become hyperactive — and why some refuse to stand down when the battle is over.

Key immune players called “helper T cells” typically help antibodies mature. If the body is invaded by a pathogen, however, these T cells can switch jobs to hunt down viruses, acting more like “killer T cells,” which destroy infected cells. When an infection is over, helper T cells usually go back to their old jobs.

In some people with severe Covid, however, helper T cells don’t stand down when the infection is over, said James Heath, a professor and president of Seattle’s Institute for Systems Biology.

About 10% to 15% of hospitalized Covid patients Heath studied had high levels of these helper T cells, which were still looking for the enemy long after it had been eliminated. He’s now studying whether these overzealous T cells might inflict damage that leads to chronic illness or symptoms of autoimmune disease.

“These T cells are still there months later and they’re aggressive,” Heath said. “They’re on the hunt.”

Friendly Fire

Covid appears to confuse multiple parts of the immune system. In some patients, Covid triggers autoantibodies that target the immune system itself, leaving patients without a key defense against the coronavirus.

In October, a study published in Science led by Rockefeller University’s Jean-Laurent Casanova showed that about 10% of Covid patients become severely ill because they have antibodies against an immune system protein called interferon.

Disabling interferon is like knocking down a castle’s gate. Without these essential proteins, invading viruses can overwhelm the body and multiply wildly.

New research shows that the coronavirus may activate preexisting autoantibodies, as well as prompt the body to make new ones. In the January study, half of the hospitalized Covid patients had autoantibodies, compared with fewer than 15% of healthy people.

Other research has produced similar findings. In a study out in December, researchers found that hospitalized Covid patients harbored a diverse array of autoantibodies.

While some patients studied had antibodies against virus-fighting interferons, others had antibodies that targeted the brain, thyroid, blood vessels, central nervous system, platelets, kidneys, heart and liver, said Dr. Aaron Ring, assistant professor of immunology at Yale School of Medicine.

Similarities With Lupus

Some patients had antibodies associated with lupus, a chronic autoimmune disorder that can cause pain and inflammation in any part of the body. Covid patients rife with autoantibodies tended to have the severest disease, said Ring, who was surprised at the level of autoantibodies in some patients.

“They were comparable or even worse than lupus,” Ring said.

Researchers would like to know if lingering autoantibodies contribute to the symptoms of “long Covid,” which afflicts one-third of covid survivors up to nine months after infection, according to a new study in JAMA Network Open.

“Long haulers” suffer from a wide range of symptoms, including debilitating fatigue, shortness of breath, cough, chest pain and joint pain. Other patients experience depression, muscle pain, headaches, intermittent fevers, heart palpitations and problems with concentration and memory, known as brain fog.

Less commonly, some patients develop an inflammation of the heart muscle, abnormalities in their lung function, kidney issues, rashes, hair loss, smell and taste problems, sleep issues and anxiety.

The National Institutes of Health has announced a four-year initiative to better understand long Covid, using $1.15 billion allocated by Congress.

Ring said he’d like to study patients over time to see if specific symptoms might be explained by lingering autoantibodies.

“We need to look at the same patients a half-year later and see which antibodies they do or don’t have,” he said. If autoantibodies are to blame for long Covid, they could “represent an unfortunate legacy after the virus is gone.”

Kaiser Health News is a nonprofit news service covering health issues. It is not affiliated with Kaiser Permanente.

Is Recreational Drug Use a Human Right?

By Roger Chriss, PNN Columnist

The book “Drug Use for Grown-Ups” by Carl Hart, PhD, is garnering a lot of attention. Hart argues that recreational drug use is a fundamental human right, while also describing the harms of drug laws and policy on people of color. His book is a mixture of anecdote and analysis that raises a lot of important issues about drugs and society.

Hart is unapologetic about his own drug use and that of others, saying that "Adults should be permitted the legal right to sell, purchase, and use recreational drugs of their choice." He sees drug use as “beneficial for human health and functioning” and causing ‘little or no harm” in most instances.

Specifically, Hart states that drug use is an "act that the government is obliged to safeguard” because it is a part of the “pursuit of happiness” in the Declaration of Independence. He claims that Thomas Jefferson, one of the authors of the Declaration, was “a long-term avid drug user.”

Hart, who is a psychology professor at Columbia University, raises numerous questions in a blunt and sometimes brusque fashion, asking “Why is it that guns can be legally purchased but heroin cannot?”

He challenges his readers with remarks like: “Few would balk at using Viagra or Cialis to enhance sexual performance, but many more find it objectionable to use drugs such as amphetamines to improve the sexual experience.”

Hart doesn't mythologize or romanticize drugs or their users, and questions why advocates of the psychedelic movement call themselves “psychonauts.”

“The term psychonaut in itself is another attempt to dissociate middle-class psychedelic users from users of drugs such as crack and heroin, who are disapprovingly called ‘crackheads’ or ‘dope fiends’.”

Hart defends this position by pointing out that nearly 80 percent of illicit drug users don’t have problems such as addiction. He explains that his own heroin use is rational: “Like vacation, sex, and the arts, heroin is one of the tools that I use to maintain my work-life balance.”

As for overdose deaths, Hart contends that contaminated drugs are the issue. “A regulated market, with uniform quality standards, would virtually put an end to contaminated drug consumption and greatly reduce fatal, accidental overdoses,” he writes.

Further, Hart states that drug addiction is not a brain disease, writing that there is no evidence indicating that “responsible recreational drug use” causes brain abnormalities. He says obsessing over addiction has caused harm by stigmatizing drug users as unworthy of social support or rehabilitative care. Hart sees the opioid crisis as overblown and rooted in racism.

“All the evidence from research clearly shows that most heroin users are people who use the drug without problems, such as addiction; they are conscientious and upstanding citizens,” he writes. “The new ‘get tough on opioids’ policies have been fueled by the mistaken perception that most illegal opioid dealers are black or Latino.”

Legalization, Hart claims, is the key to changing all this. Prohibition of alcohol gave birth to criminal gangs and a thriving underground market in booze, some of it so contaminated with impurities it made people sick or even killed them. “This problem went away when Prohibition was repealed,” he points out.

But not all of this holds up so well. Hart argues that a legalized market with regulated substances would keep people safe, but he himself chooses to use an illicit substance called “hex” of unknown provenance and effect while at a drug festival.

“I now include hex among the drugs I might want to take immediately before attending some awful required social event, such as an academic reception or an annual departmental holiday party,” he wrote.

Hart’s book is also notable for what it lacks. He doesn’t look at public health data or long-term studies on drug risks and user outcomes in the U.S. or other countries, and ignores animal research on drug risks and harms.

Hart also omits recent discouraging research on drug legalization and social justice. According to the University of Washington’s Alcohol & Drug Abuse Institute, legalization of cannabis has had no impact on reducing racial bias in policing and other disparities in the criminal justice system.   

He also doesn’t discuss the under-treatment of pain in people of color due to myths about higher pain tolerance, lack of nerve endings, or greater abuse and addiction risk.

Hart clearly shows the harms of current drug policy, but arguably overstates the potential benefits of legalization. And his blunt style sometimes diminishes his own credibility.  Overall, the book “Drug Use for Grown-Ups” adds to the discussion of drug policy in the U.S. by asking some challenging questions, but doesn’t resolve many important issues.

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.

“Drug Use for Grown-Ups” is featured in PNN’s Suggested Reading section, along with other books on pain treatment and drug policy.

It’s Time for People in Pain To Be Heard

By Carol Levy, PNN Columnist

I just had my second “there's an issue with filling your codeine prescription” incident.

I have been on codeine, on and off, for over 30 years. Initially, I was allowed refills. When that was no longer permitted, my doctor gave me a new prescription, each and every month, for 120 pills.

When my trigeminal neuralgia pain became somewhat better as a result of various surgeries, I often took only 1 or 2 pills per day.

I am now about 90% housebound. Part of it is due to Covid, but mostly it’s because I do not want to go out and make the baseline pain worse. As a result, some days I take no codeine at all. My last prescription was for 120 pills. It was a month’s supply that lasted for 9 months.

The first incident was last year, when my pain management doctor decided, without discussing it with me, that he was no longer writing scripts for 120 codeine pills a month. Instead, he changed it to 10 pills a month.

I was told he didn’t like me having extra pills, a nonsensical excuse as I had no history of giving them away or taking too many. Prescriptions for 120 pills just made it easier for everyone, including the insurance company, since they would be paying less for fewer doctor appointments.

Fortunately, I was able to go to my family doctor, who had no problem writing for 120 pills. They trusted me there, knowing I would not abuse them.

But when I took the script to the pharmacy, I was told, “We can only fill a 7-day supply per your insurance company.”

The worst part about that was not that I would have to repeatedly go back to the pharmacy, but that the cost for each 7-day supply was much more for me out-of-pocket than if they just filled the whole prescription at once.

My Physician Assistant called the insurance company to ask for a pre-authorization. This would allow the pharmacy to fill the entire amount at one time. They immediately allowed it for the next 12 months, which seemed odd.

If they think I should only be getting a 7-day supply, then why allow the whole script to be filled for an entire year? Either I am untrustworthy or I'm not.

I am lucky. I don’t rely on daily opioids to get me out of bed, go to the store or be able to work. So many of us have no other option but to take them. My annoyance is tame compared to what other patients go through, who have been unable to get what they need due to restrictions on prescribing.

Physicians for Responsible Opioid Prescribing (PROP) recently sent a letter to the AMA saying the organization shouldn’t be calling for changes in the CDC opioid guideline, even though far more people are dying from street drugs than prescription opioids.

“Medically prescribed opioids remain a common gateway to illicit opioid use and are themselves frequent causes of opioid addiction and overdose, even if illicit opioids currently cause the greater number of deaths,” PROP said.

PROP founder Dr. Andrew Kolodny even said that prescriptions “still have a very long way to go” and should be reduced even further.

PROP’s reach is loud and strong. We complain so much to each other, patient support groups, Twitter and other social media about how awful this is, how unfair and inhumane.

A number of people have started online petitions to send to the FDA or CDC, asking that the guidelines be changed so they stop hurting chronic pain patients. Many say, “This is a great idea.” Yet few actually sign.

Nothing will change if we don’t band together and make our voices heard. The call keeps going out, “Something must be done!” But too often the answer is, “Oh yes, somebody must do something. But I'm too busy.”

Whispering in the wind won’t help. It is long past time for us to become a true force, with a voice that is louder and stronger than PROP’s. 

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.

New European Guideline Says Opioids ‘Do Not Work’ for Many Types of Chronic Pain

By Pat Anson, PNN Editor

Calling opioid medication a “two edged sword,” the European Pain Federation (EFIC) has released new guidelines that strongly recommend against using opioids to treat fibromyalgia, low back pain, migraine, irritable bowel syndrome and other types of chronic non-cancer pain.

“The new recommendations advise that opioids should not be prescribed for people with chronic primary pain as they do not work for these patients,” the EFIC said in a statement.

However, the guideline states that low doses of opioids may be suitable for treating “secondary pain syndromes” caused by surgery, trauma, disease or nerve damage, but only after exercise, meditation and other non-pharmacological therapies are tried first.

“Opioids should neither be embraced as a cure‐all nor shunned as universally dangerous and inappropriate for chronic noncancer pain. They should only be used for some selected chronic noncancer pain syndromes if established non‐pharmacological and pharmacological treatment options have failed,” the guideline states. “In this context alone, opioid therapy can be a useful tool in achieving and maintaining an optimal level of pain control in some patients.”

Opioid pain relievers are not as widely used in Europe as they are in the United States or Canada. The EFIC said it was trying to “allay concerns over an opioid crisis” developing in Europe, as it has in North America.       

“As the leading pain science organisation in Europe, it is crucial that EFIC sets the agenda on issues such as opioids, where there are growing societal concerns. These recommendations clarify what role opioids should play in chronic pain management,” EFIC President Brona Fullen said in a statement.

The guideline’s lead author, Professor Winfried Häuser, said he and his colleagues tried to strike a middle ground on the use of opioids.

“The debate on opioid-prescribing for chronic non-cancer pain has become polarized: opioids are either seen as a dangerous risk for all patients, leading to addiction and deaths, or they are promoted as most potent pain killers for any type of pain,” said Häuser, who is an internal medicine specialist in Germany.

“Opioids are still important in the management of chronic non-cancer pain – but only in some selected chronic pain syndromes and only if established non-pharmacological and non-opioids analgesics have failed or are not tolerated.”

PROP Consulted for European Guideline

The guideline was developed by a 17-member task force composed of European experts in pain management, including 9 delegates selected by EFIC’s board “who advocate and who are critical with the use of opioids.” Only one delegate from Pain Alliance Europe represented patients.

The recommendations developed by the task force were reviewed by five outside experts, including Drs. Jane Ballantyne and Mark Sullivan, who belong to Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group in the U.S.  Ballantyne is PROP’s President, while Sullivan is a PROP board member. Several changes suggested by the outside experts were adopted.

Coincidentally, Ballantyne, Sullivan and three other PROP board members were involved in the drafting of the opioid guideline released in 2016 by the U.S. Centers for Disease Control and Prevention. That controversial guideline is now being rewritten by the CDC after voluminous complaints from patients and doctors that the recommendations led to forced tapering, withdrawal, uncontrolled pain and suicides.

Sullivan and two other PROP board members were also involved in drafting Canada’s 2017 opioid guideline, which was modeled after the CDC’s and provoked similar complaints from Canadian pain patients.

90 MME Recommended Limit

The CDC and Canadian opioid guidelines appear to have been used as resources by the EFIC task force, which adopted many of the same recommendations, even while acknowledging the low quality of evidence used to support them.   

One recommendation is straight out of the CDC guideline, advising European doctors to “start low and go slow.” Prescribers are urged to start patients on low doses of 50 morphine milligram equivalents (MME) or less a day and to avoid increasing the dosage above 90 MME/day.

One significant difference with the North American guidelines is that the EFIC recommends that opioids not be prescribed for fibromyalgia, migraines and other chronic “primary pain” conditions for which there is no known cause – suggesting those disorders have an emotional or psychological element that will lead to opioid abuse.

“Prescription of high doses of opioids to patients with primary pain syndromes might have been a factor driving the opioid crisis in North America,” the EFIC guideline warns.

“This was further compounded by patient characteristics that included physical and psychological trauma, social disadvantage and hopelessness that served as a trigger for reports of pain intensity prompting prescriptions of more opioids.”

Secondary pain conditions for which opioids “can be considered“ include multiple sclerosis, stroke, restless leg syndrome, Parkinson’s disease, rheumatoid arthritis, phantom limb pain, non-diabetic neuropathy, spinal cord injuries and Complex Regional Pain Syndrome (CRPS). 

Unlike the North American guidelines, the EFIC acknowledges that there are physical and genetic differences between patients. Some patients who are rapid metabolizers “might require higher dosages of opioids than the ones recommended by the guidelines.“

EFIC GRAPHIC

The EFIC also warns that its guideline should not be used to justify abruptly tapering or discontinuing opioids for anyone already prescribed at higher dosages. The recommendations are also not intended for the management of short-term acute pain, sickle cell disease or end-of-life care.

Individualized Pain Care After Surgery Raises Patient Satisfaction

By Pat Anson, PNN Editor

An opioid prescribing guideline tailored to a patient’s specific needs – that doesn’t take a one-size-fits-all approach – resulted in high patient satisfaction rates and reduced the use of opioids after surgery.

The post-operative pain management guideline was developed by surgeons at Dartmouth-Hitchcock Medical Center in New Hampshire, who based the number of opioid pills sent home with patients on how many they needed the day before they were discharged from the hospital. Other guidelines typically base the number of pills on the type of operation that was performed and do not take into account a patient’s individual needs.

“In this new prospective study we found that 93 percent of patients had their post-surgery opioid needs satisfied,” said lead author Richard Barth Jr., MD, section chief of general surgery. “This finding means that this guideline can be used for a wide variety of operations to guide surgeons on how many opioids to prescribe when sending patients home after surgery.”

Barth and his colleagues enrolled 229 patients in the study who had elective general surgery, including colorectal, gynecological, thoracic and urological operations. Upon discharge, patients received prescriptions for acetaminophen and ibuprofen, as well as opioids, based on the guideline.

If they needed no opioids the day before discharge, they were sent home with the morphine milligram equivalent (MME) of five oxycodone 5mg pills. If they took one or three pills, they were given a prescription for 15 more. And if they needed four or more pills, they were given a prescription for 30 pills.  

Patient satisfaction was highest among those who needed the fewest number of pills. Despite being given an opioid prescription, 73 percent of the patients who were prescribed five pills used no opioids at home, and 85 percent used two pills or less.

In all, 60 percent of patients in the study had leftover opioid pills, according to findings published in the Journal of the American College of Surgeons. They were given instruction on how to dispose of them safely.

Barth says surgeons played a pivotal role in minimizing opioid use by talking to patients before surgery and setting their expectations for pain management. They told patients they were likely to be discharged with either no opioids or a small amount based on their opioid use in the hospital.

“The other part of that discussion involves letting patients know that they should expect some pain, that our goal isn’t to get rid of every last bit of their pain,” Barth said. “That was something that surgeons tried to accomplish years ago, but that’s not what we’re aiming for now. A low level of discomfort is acceptable, and patients need to have that expectation.”

That process also including prescribing, not just recommending, over-the-counter pain relievers.  

“By prescribing non-opioid analgesics, the surgeon sets the expectation that they should be used,” he said. “It’s a big difference if a surgeon prescribes non-opioid analgesics compared with just recommending that a patient take acetaminophen or ibuprofen that they might have at home.” 

In recent years, many U.S. hospitals have adopted policies that reduce or completely eliminate the use of opioids after surgery. Those policies unfairly leave some patients in pain, according to a recent study presented at the annual meeting of the American College of Surgeons. Researchers found that about half of patients need opioid medication after major surgeries.

“Our goal is to give them the exact right amount so that we limit the number of un-used opioids in our community while also making sure we don’t reduce it down too far and then leave them in pain,” said lead author Cornelius Thiels, DO, a surgical oncology fellow at Memorial Sloan Kettering Cancer Center.

“The right answer may be more non-opioid based pain medications, better patient education and setting of expectations, or in some cases patients may actually require slightly more opioid medications, and that is OK.”

Medical Cannabis Linked to Rebound Headaches

By Pat Anson, PNN Editor

Medication overuse headache, also known as “rebound” headache, is a common problem for people who frequently use pain medication to relieve headaches and migraine.

According to the American Migraine Foundation, rebound headaches can be triggered by a wide assortment of analgesics, from aspirin and triptans to acetaminophen and opioids. Even caffeine can cause a rebound headache if you consume more than 200mg a day – about two cups of coffee.     

So perhaps it’s not surprising that medical cannabis is also associated with medication overuse headache, according to a preliminary study by researchers at Stanford University School of Medicine.

“Many people with chronic migraine are already self-medicating with cannabis, and there is some evidence that cannabis can help treat other types of chronic pain,” said study author Niushen Zhang, MD, a neurologist who is director of Stanford’s Headache Fellowship Program.

“However, we found that people who were using cannabis had significantly increased odds of also having medication overuse headache, or rebound headache, compared to people who were not using cannabis.”

Zhang and her colleagues looked at the medical records of 368 people who had chronic migraine -- which is 15 or more headache days per month. Less than half were using medical cannabis

Researchers found the cannabis users were six times more likely to have rebound headaches than those who did not use cannabis. People who used cannabis were also more likely to take opioids.  Previous research has found that opioids and cannabis can both influence the part of the brain called the periaqueductal gray, which has been linked to migraine.

Zhang’s study will be presented at the American Academy of Neurology’s annual meeting next month.

Medical cannabis has become a trendy alternative to pharmaceuticals for treating migraine, with research showing that both inhaled and ingested cannabis can reduce migraine pain. 

A recent study of nearly 10,000 people in the U.S. and Canada who used a migraine tracking app found that 82 percent who used cannabis believed it was an effective pain reliever.    

A 2017 study conducted in Israel found that combining THC and CBD in an oral dose was just as effective in treating migraine pain as amitriptyline – a tricyclic antidepressant commonly prescribed for migraine.

And a 2016 study at the University of Colorado found that cannabis significantly reduced the number of migraine headaches. Inhalation appeared to provide the fastest results, while edible cannabis took longer to provide pain relief.

About a billion people worldwide suffer from migraine headaches, which affect three times as many women as men. Over 37 million people in the United States live with migraines, according to the American Migraine Foundation.

Don't Get Picky: All Three Covid Vaccines Highly Effective

By Arthur Allen and Liz Szabo, Kaiser Health News

When getting vaccinated against Covid-19, there’s no sense being picky. You should take the first authorized vaccine that’s offered, experts say.

The newest Covid vaccine on the horizon, from Johnson & Johnson, is probably a little less effective at preventing sickness than the two shots already being administered around the U.S., from Pfizer-BioNTech and Moderna.

The Food and Drug Administration authorized the Johnson & Johnson vaccine after reporting it showed about 66% effectiveness at preventing Covid illness in a 45,000-person trial. No one who received the vaccine was hospitalized with or died of the disease, according to the data released by the company and FDA. As many as 4 million doses could be shipped out of J&J’s warehouses beginning this week.

The J&J vaccine is similar to the shots from Moderna and Pfizer-BioNTech, but uses a different strategy for transporting genetic code into human cells to stimulate immunity to the disease. The Moderna and Pfizer-BioNTech vaccines were found in trials last fall to be 94% effective in preventing illness caused by Covid. They also prevented nearly all severe cases.

But the difference in those efficacy numbers may be deceptive. The vaccines were tested in different locations and at different phases of the pandemic. And J&J gave subjects in its trial only one dose of the vaccine, while Moderna and Pfizer have two-dose schedules, separated by 28 and 21 days, respectively. The bottom line, however, is that all three do a good job at preventing serious Covid.

“It’s a bit like, do you want a Lamborghini or a Chevy to get to work?” said Dr. Gregory Poland, director of the Mayo Clinic’s Vaccine Research Group, who was a paid consultant in the J&J study. “Ultimately, I just need to get to work. If a Chevy is available, sign me up.”

“From a personal and public health perspective, the best advice for now is to get whatever you can as soon as you can get it, because the sooner we all get vaccinated the better off we all are,” said Dr. Norman Hearst, a family doctor and epidemiologist at the University of California-San Francisco.

Of the 10 people who got severe disease in the Pfizer trial, nine had received a placebo, or fake vaccine; none of the 30 severe cases in the Moderna trial occurred in people who got the true vaccine. A month after receiving the Johnson & Johnson shot there were no deaths or hospitalizations in those who had been vaccinated.

“The real goal is to keep people out of the hospital and the ICU and the morgue,” said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “This vaccine will do that well.”

J&J Vaccine Tested Against Variants

The data that Moderna and Pfizer-BioNTech presented to the FDA for their vaccines came from large clinical trials that took place over the summer and early fall in the United States. At the time, none of the new variants of Covid — some of which may be better at evading the immune responses produced by vaccines — were circulating here.

In contrast, the J&J trial began in September and was put into the arms of people in South America, South Africa and the United States. The J&J vaccine was 72% effective against moderate to severe Covid in the U.S. part of the trial, compared with 57% in South Africa, where a more contagious mutant virus is the dominant strain.

The Moderna and Pfizer-BioNTech vaccines might not have gotten the same sparkling results had they been tested more recently — or in South Africa.

“This vaccine was tested in the pandemic here and now,” said Dr. Dan Barouch, a Harvard Medical School professor whose lab at the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston developed the J&J vaccine. “The pandemic is a much more complex pandemic than it was several months ago.”

The J&J vaccine appears to have some other advantages. First, it seems to cause fewer serious side effects like the fever and malaise suffered by some Pfizer-BioNTech and Moderna vaccine recipients. High fever and dehydration are particular concerns in fragile elderly people who “have one foot on the banana peel,” said Dr. Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program. The J&J vaccine “may be a better vaccine for the infirm.”

Many people may prefer the J&J shot because “it’s one and done.” It’s easier for administrators too: just one appointment to schedule.

The J&J vaccine can also be stored in regular refrigerators, while the Pfizer and Moderna vaccines have to be stored in freezers and must be used or discarded within six hours after the vial is opened. Vials of the J&J vaccine can be restored in a refrigerator for later use if doses remain.

“Right now we have mass immunization clinics that are open but have no vaccine,” said Offit. “Here you have a single-dose regime with easy storage and handling.”

Ultimately, a person’s address — not their personal preference — may determine which vaccine they receive, said E. John Wherry, director of the Institute for Immunology at the University of Pennsylvania’s Perelman School of Medicine. He pointed out that the Johnson & Johnson vaccine is a simpler choice for rural areas.

“A vaccine doesn’t have to be 95% effective to be an incredible leap forward,” said Wherry. “When we get to the point where we have choices about which vaccine to give, it will be a luxury to have to struggle with that question.”

Kaiser Health News is a nonprofit news service covering health issues. It is not affiliated with Kaiser Permanente.