Misuse of Rx Opioids by Young Adults Falls to Record Lows

By Pat Anson, PNN Editor

The misuse of prescription opioids by young adults has fallen to the lowest levels ever recorded, according to an annual survey that’s been tracking drug use in the U.S. since 1975. The Monitoring the Future (MTF) survey also found that use of marijuana and hallucinogens by young adults rose to an all-time high last year.

The MTF survey and annual report is a joint project of the National Institute on Drug Abuse (NIDA) and the University of Michigan. Over 28,000 people were surveyed last year, including young adults aged 19 to 30 and adults aged 35 to 60.

Only 1.7% of young adults reported using “narcotics other than heroin,” a poorly named category that refers to the non-medical use of prescription opioids such as hydrocodone and oxycodone. Misuse of prescription opioids has been in a steep decline since reaching a peak of 8.9% in 2006.

NON-MEDICAL USE OF Rx OPIOIDS BY YOUNG ADULTS AGED 19-30

Source: Monitoring the Future

“One of the best ways we can learn more about drug use and its impact on people is to observe which drugs are appearing, in which populations, for how long and under which contexts,” said Megan Patrick, PhD, a research professor and principal investigator of the MTF study. 

“Monitoring the Future and similar large-scale surveys on a consistent sample population allow us to assess the effects of ‘natural experiments’ like the pandemic. We can examine how and why drugs are used and highlight critical areas to guide where the research should go next and to inform public health interventions.”

The MTF survey reflects the declining role that prescription opioids have in the U.S. drug epidemic, which is primarily fueled by illicit fentanyl and other street drugs. According to the IQVIA Institute, a healthcare data tracking firm, prescription opioid use has fallen by 48% over the past five years and now stands at levels last seen in 2000.

Once the most widely prescribed drug in the United States, hydrocodone (Vicodin) prescriptions have plummeted since the opioid was reclassified as a Schedule II Controlled Substance in 2014 and became harder to obtain.

According to the MTF survey, only 1.3% of young adults reported using Vicodin last year, down from a peak of 9.2% in 2009.

VICODIN USE BY YOUNG ADULTS AGED 19-30

Source: Monitoring the Future

Marijuana and Hallucinogens

While fewer younger adults are misusing prescription opioids, they are using marijuana and hallucinogens far more often.

Daily marijuana use (use on 20 or more occasions in the past 30 days) in 2021 reached the highest levels ever recorded since the MTF survey started monitoring it in 1988. Daily marijuana use was reported by 11% of young adults last year, up from 8% in 2016 and 6% in 2011.

In 2021, 8% of young adults reported using a hallucinogen such as LSD, ecstasy or psilocybin, an all-time high since the category was first surveyed in 1988. By comparison, only 3% reported using hallucinogens a decade earlier.

“As the drug landscape shifts over time, this data provides a window into the substances and patterns of use favored by young adults. We need to know more about how young adults are using drugs like marijuana and hallucinogens, and the health effects that result from consuming different potencies and forms of these substances,” NIDA Director Nora Volkow, MD, said in a news release.

“Young adults are in a critical life stage and honing their ability to make informed choices. Understanding how substance use can impact the formative choices in young adulthood is critical to help position the new generations for success.”

Alcohol remains the most-used substance among young adults, by far, with nearly 82% reporting alcohol use last year, unchanged from 2020. However, binge drinking (five or more drinks) rebounded to 32% in 2021 from an historic low in 2020, during the early stages of COVID-19 pandemic. 

Fewer Opioids and Weaker Doses for Cancer Patients

By Pat Anson, PNN Editor

Another study has documented how opioid guidelines over the past decade have led to fewer and weaker opioid prescriptions for cancer patients --- even though the treatment guidelines typically state they are not intended for patients suffering from cancer pain.

In findings recently published in PLOS ONE, researchers at Johns Hopkins Bloomberg School of Public Health and the University of Michigan analyzed pharmacy claims for up to 53 million privately insured U.S. adults from 2012 to 2019. During that period, opioid prescribing fell from 49.7% to 30.5% for people with chronic non-cancer pain (CNCP) and from 86% to 78.7% for people with cancer.

While the drop in prescribing appears minor for cancer patients, a closer look at the numbers shows a significant decline in high dose prescriptions and in the number of days opioids were prescribed.

In 2012, for example, the average daily dose for a cancer patient was 62.4 morphine milligram equivalents (MME). By 2019, that had fallen to 44.7 MME – a decline of over 28 percent.

The percentage of cancer patients getting over 90 MME — a ceiling recommended by the CDC for chronic non-cancer pain — fell from 26.2% to just 7.6% -- a 71 percent decrease.

The average number of days per year a cancer patient received opioids also fell, from 34.8 days to 22.3 days – a 36 percent decline.

“While clinical guidelines continue to endorse prescription opioid treatment for cancer-related pain, declines in receipt of any opioid prescription were observed for people with cancer diagnoses, though these declines were smaller in magnitude than those observed among people with CNCP diagnoses. Future research is needed to understand the clinical implications of this decline, as well as observed decreases in MME/day and days’ supply of opioid prescriptions, among cancer patients,” researchers reported.

In short, cancer patients are getting smaller and fewer doses of opioids, which researchers admit could be making their cancer pain worse. However, they stopped short of sounding the alarm over that trend and suggest it could be beneficial – by helping to reduce the risk of cancer patients overdosing.  

“On the one hand, this finding may signal a cooling effect on opioid prescribing that could contribute to poorly controlled cancer pain. On the other hand, this finding may suggest reductions in high-risk opioid prescribing practices, such as high dosage prescribing, which are shown to contribute to increased risk of opioid overdose death among cancer patients,” they wrote.

Oncology experts have been warning for years that opioid prescribing guidelines are being misapplied to cancer patients, even to women with advanced breast cancer.

In 2019, a Rite Aid pharmacist refused to fill an opioid prescription for April Doyle, a California woman with Stage 4 terminal breast cancer.  A tearful video she posted online went viral and the pharmacy apologized to Doyle, who later died.

That same year, the Cancer Action Network warned there has been “a significant increase in cancer patients and survivors being unable to access their opioid prescriptions.” One out of four said a pharmacy had refused to fill their prescriptions and nearly a third reported their insurer refused to pay them.

Part of the confusion about what’s appropriate for cancer pain is that the CDC’s opioid guideline says the recommendations are intended for patients “who have completed cancer treatment, are in clinical remission, and are under cancer surveillance only.”  Experts say the inclusion of cancer survivors is a mistake because it is not uncommon for pain to persist long after the cancer is treated or even because of the treatment itself.  

A revised draft version of the CDC guideline attempts to clear up some of the confusion by explicitly stating the recommendations are not intended for patients undergoing “cancer pain treatment” and for those in palliative or end-of-life care. The updated version of the CDC guideline is expected to be published late this year.

Should Gabapentin Be Used for Dental Pain?

By Pat Anson, PNN Editor

Since it was first approved as an anti-seizure medication in the 1990’s, gabapentin (Neurontin) has become one of the most widely studied and prescribed drugs in world.  Although gabapentin is only approved by the FDA for epilepsy and postherpetic neuralgia (shingles), it is widely prescribed off-label for fibromyalgia, neuropathy and many other types of pain.

Hundreds of clinical trials have been conducted to find new uses for gabapentin -- for everything from asthma and obesity to alcoholism and improving your sex life. Gabapentin has been pitched for so many different conditions that a drug company executive infamously called it “snake oil.”

Now gabapentin is being touted as a “promising alternative” to opioids for dental pain. In a new study at the University of Rochester Medical Center’s Eastman Institute for Oral Health (EIOH), researchers found that gabapentin, when combined with ibuprofen or acetaminophen, was more effective than opioids in relieving pain after tooth extractions.  

“We hypothesized that using a combination of the non-opioid pain medications and adding gabapentin to the mix for pain would be an effective strategy to minimize or eliminate opioids for dental pain,” said Yanfang Ren, DDS, a dentistry professor at EIOH.   

Ren and his colleagues treated over 7,000 patients at an urgent dental care clinic with different combinations of opioids, ibuprofen, acetaminophen and gabapentin after tooth extractions. The “failure rates” of the medications were determined by how often patients returned to the clinic for additional pain relief.

The study findings, published in JAMA Network Open, found that non-opioid medications, including those with gabapentin, had failure rates significantly lower than opioids.      

Dental Pain Failure Rates

• 0.9% Acetaminophen/ibuprofen

• 3.4% Gabapentin/acetaminophen

• 5.3% Gabapentin/ibuprofen

• 9.2% Codeine/acetaminophen

• 19.4% Hydrocodone/acetaminophen

• 31.3% Other opioid combinations

Providers at the dental clinic have already put their findings into practice by sharply reducing the use of opioids. Prior to that, about 1,800 patients at the clinic were treated each year with opioids. Researchers estimate the reduced opioid prescribing may have prevented 105 of those patients from developing a problem with “persistent opioid use.”

“This study represents continued efforts by our team and other dentists to minimize the use of opioids for dental pain,” said Eli Eliav, DMD, the director of EIOH. “Additional studies, preferably randomized controlled clinical trials, are needed to confirm the safety and effectiveness of this approach. It is our duty to continuously seek safe and effective treatment for our patients in pain.”

Gabapentin has issues of its own. Patients prescribed gabapentin often complain of mood swings, depression, dizziness, fatigue and drowsiness, and a 2019 review found little evidence gabapentin should be used off-label to treat pain. There are also many reports that gabapentin is being abused and sold on the streets because it can heighten the effects of other drugs.

Evidence Used to Justify CDC Opioid Guideline ‘No Longer Present’

By Pat Anson, PNN Editor

Anti-opioid activists and public health officials have long argued that opioid “overprescribing” fueled the overdose crisis in the United States, causing drug deaths to surge to record levels.

“This rise is directly correlated with increased prescribing for chronic pain,” Dr. Jane Ballantyne, then-president of Physicians for Responsible Opioid Prescribing (PROP), wrote in a 2015 letter to the National Institutes of Health.

That claim was repeated the following year by the CDC when the agency released its controversial opioid guideline. “Overprescribing opioids – largely for chronic pain – is a key driver of America’s drug overdose epidemic,” then-CDC director Dr. Thomas Frieden said in a news release.   

But a new analysis debunks the overprescribing myth, finding the “direct correlations” cited by Frieden, Ballantyne and others are no longer valid, if they ever were.

In a study recently published in Frontiers of Pain Research, independent researchers Larry Aubry and B. Thomas Carr examined opioid prescribing trends and overdose deaths from 2010 to 2019, using the same data sources that the CDC guideline is based on.

“The direct correlations used to justify the CDC guideline… are no longer present,” they reported.

Aubry and Carr found that opioid prescribing, when measured in morphine milligram equivalents (MME), was in steep decline years before the guideline was even released. That trend accelerated even further when regulators, insurers and healthcare providers started following the CDC’s recommendations.

If the overprescribing theory were true, you would expect drug deaths to go down as opioid sales did. But in subsequent years, overdoses linked to prescription opioids stayed flat and drug deaths surged even higher. In research terms, that is known as a “negative correlation” -- a trend not supported by facts.

Looking at data from all 50 states, Aubry and Carr found “significant negative correlation” in 38 states between overdoses and prescription opioids, and a positive correlation in only 2 states. In 10 states, there appeared to be no relationship at all. That calls into question ones of the primary recommendations of the CDC guideline; that daily opioid doses not exceed 90 MME.

“This recommendation is not supported by the available data. Regression analyses of (total opioid deaths, opioid overdose deaths, opioid treatment admissions, and prescription opioid sales) among patients receiving doses of at least 90 MME/day show significant negative relationships, indicating that lower (prescription opioid sales) in this high-dosage cohort do not correspond to lower death rates,” Aubry and Carr reported.

The CDC estimates that over 107,000 people died of overdoses in 2021, well above the 63,600 drug deaths reported in 2016, the year the guideline was released.

Negative Correlation Between Overdoses and Opioid Prescribing

sOURCE: FRONTIERS OF PAIN RESEARCH

Patient Outcomes Not Being Monitored

Even more concerning is that the CDC does not appear to be tracking the impact of its 2016 guideline on pain patients, even as it prepares a long-delayed update to the guideline. As PNN has reported, the CDC ignored warnings from its own consultants that the agency “should consider conducting more research” on patients, many of whom were abruptly tapered or abandoned by their doctors after the guideline’s release.

“Reasonable judgment would dictate tracking and reporting of chronic pain patient outcomes (deaths, suicides, returns in benefits, reported pain, function, etc.) for individuals since the guideline or the guideline update. However, there appears to be no publicly available evidence that a monitoring process is required or is planned to measure and confirm outcomes,” Aubry and Carr wrote.

PROP is not following the data either. In a recent debate, PROP board member Adriane Fugh-Berman claimed that pain patients addicted to prescription opioids were still fueling the overdose epidemic, even though illicit fentanyl and other street drugs are linked to the vast majority of deaths.

“Those patients went to the street. They got addicted to heroin. The reason those deaths went up is because the illicit supply of opioids has become laced with fentanyl and has become highly dangerous,” Fugh-Berman said, without citing any evidence. “It’s not that prescription opioids have nothing to do with it.  Many patients started on prescription opioids ended up on the streets looking for heroin. They’re dying because the illicit opioid products have become extremely dangerous. That’s what’s killing people.”

Fugh-Berman is not an unbiased observer. She and at least five other PROP board members have testified as paid expert witnesses in opioid litigation cases, making as much as $850 an hour for their testimony blaming drug makers for the opioid crisis.

A recent analysis of overdose deaths in 2020 found that prescription opioids ranked well behind illicit fentanyl, alcohol, cocaine, methamphetamine and heroin as the leading cause of drug deaths.   

At least one critic of opioid prescribing feels it’s time to change the focus on why so many Americans are overdosing. Beth Macy, who wrote the best-selling book “Dopesick,” says drug use has changed. 

“At this point, too much attention is focused on stemming the oversupply of prescription opioids. We now have a generation of drug users that started with heroin and fentanyl.”

— Beth Macy, author of "Dopesick"

“At this point, too much attention is focused on stemming the oversupply of prescription opioids,” Macy writes in her new book, ‘Raising Lazarus.’ “We now have a generation of drug users that started with heroin and fentanyl.”

As for the CDC, a spokesperson tells PNN the agency won’t publish its guideline revision until late this year, nearly seven years after the original guideline was released. 

“CDC is currently in the process of revising the draft update to the 2016 Guideline based on comments received during the public comment period and peer review. We anticipate the final Guideline will be released later this year,” the spokesperson said.

Computer Algorithms Improve Timeliness of Overdose Data

By Pat Anson, PNN Editor

An automated process using computer algorithms to analyze death certificates would speed up and improve data collection on drug overdose deaths, according to a new study by UCLA researchers.

The current system used to track U.S. overdose deaths relies on medical examiners and county coroners – including some with little medical training -- to determine the cause of death and drugs involved. Death certificates are then sent to local jurisdictions or the Centers for Disease Control and Prevention, which codes them according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition (ICD-10).

The coding process is manual and time consuming, resulting in delays of several months before the deaths are included in CDC overdose data. With drug deaths at record levels and more dangerous substances entering the illicit drug supply, researchers say that antiquated system delays an effective public health response.

"The overdose crisis in America is the number one cause of death in young adults, but we don't know the actual number of overdose deaths until months after the fact," said lead author David Goodman-Meza, MD, assistant professor of medicine in the division of infectious diseases at the David Geffen School of Medicine at UCLA.

"We also don't know the number of overdoses in our communities, as rapidly released data is only available at the state level, at best. We need systems that get this data out fast and at a local level so public health can respond. Machine learning and natural language processing can help bridge this gap."

Goodman-Meza and his colleagues used computer algorithms to analyze the text for keywords in nearly 35,500 death certificates from nine U.S. counties in 2020. The counties include major cities such as Chicago, Los Angeles, San Diego and Milwaukee.

The researchers say their automated system demonstrated “excellent diagnostic performance” in classifying the drugs involved in overdoses.

“We found that for most substances evaluated, the performance of these algorithms was perfect or near perfect. These models could be used to automate classification of unstructured free-text, thus avoiding the manual and time-consuming process of individually reading each entry and classifying them to a specific substance,” researchers reported in JAMA Network Open.

“Excellent performance was shown for multiple substances, including any opioid, heroin, fentanyl, methamphetamine, cocaine, and alcohol using models for general text. Yet for prescription opioids and benzodiazepines, there was a considerable performance gap.”

That “performance gap” is due in part to weaknesses in the drug classification system, which lumps many synthetic opioids under the same ICD-10 code, including fentanyl, fentanyl analogs, tramadol and buprenorphine – a semi-synthetic opioid used in the addiction treatment drug Suboxone.

In the past, CDC has classified all drug deaths using that code as “prescription opioid overdoses” even though the drugs may have been illicit --- which is the case for the vast majority of deaths involving fentanyl. This resulted in government estimates of prescription opioid overdoses being significantly inflated for many years.

Using the computer algorithms developed at UCLA, prescription opioids ranked far behind fentanyl, alcohol and other substances identified as the cause of death in 8,738 overdoses.

Drugs Involved in 2020 Overdose Deaths in 9 U.S. Counties

Source: JAMA Network Open

Until recently, there was a 6-month time lag in drug deaths being counted in the CDC’s monthly Provisional Drug Overdose Death Counts report. The timeliness of the reports were improved earlier this year to a 4-month delay, but Goodman-Meza says they could be improved even more.  

"If these algorithms are embedded within medical examiner's offices, the time could be reduced to as early as toxicology testing is completed, which could be about three weeks after the death," he said.

Epidural Shortages Impacting Pain Management Worldwide

By Pat Anson, PNN Editor

Global shortages of epidural catheters and contrast dye used in medical imaging are forcing some healthcare providers to ration or postpone epidural procedures, which are commonly used to relieve back pain, labor pain and as spinal anesthesia for some surgeries.

At present, most of the catheter shortages are being reported by hospitals in Canada, with anecdotal reports of shortages in the United States. Epidural catheters are thin plastic tubes that are inserted into the lower back by a needle to allow physicians to deliver steroids and other pain medications to the spinal area.

Health Canada last week added Flex-Tip epidural catheterization kits to its list of medical device shortages. The shortage began on July 18 and is expected to continue until the end of the year. The epidural kits are made by Arrow International of Pennsylvania, which did not respond to a PNN request for comment.

The Vice-President of the Canadian Anesthesiologists’ Society said most of the shortages are in western Canada, and that healthcare providers are frustrated by a lack of information from catheter manufacturers and Health Canada.

“If the shortage is global, maybe it wouldn’t make a difference. But I do think that on the communication side, on the supply-chain side and the protocols that exist, there’s room for improvement,” Dr. Lucie Filteau told The Canadian Press. “We thought there were just isolated little pockets, and people started to become aware that it was more widespread.”

In May, an international supplier of epidural kits in the UK announced a disruption to its supply due to shortages of a blue dye used in tubing. The disruption was projected to last until July, but appears to be ongoing. Australia’s Therapeutic Goods Administration recently issued an alert warning of “temporary supply issues affecting popular brands of epidural kits in overseas markets.”

“We have anecdotally heard of shortages,” a spokesperson for the American Society of Anesthesiologists told PNN when asked about catheter shortages in the U.S. The organization was planning to survey its members to get a better idea of the extent of the problem. The U.S. Food and Drug Administration does not currently have epidural catheters on its list of medical device shortages.

Epidurals are widely used in the U.S. and Canada to relieve pain during labor and cesarean sections. The injections numb the lower part of the body, allowing expectant mothers to remain awake during child birth. Nitrous oxide – more commonly known as laughing gas – can be used as an alternative to epidurals.

In addition to treating labor pain, epidural injections are widely used for back pain. About 9 million epidural steroid injections are performed annually in the U.S., even though they are not FDA-approved. The FDA has warned that injection of steroids into the epidural space can result in rare but serious neurological problems, including loss of vision, stroke and paralysis.

Meanwhile, a global shortage of contrast dyes that began in April due to COVID-related supply chain disruptions in China appears to be easing. Contrast dyes — also known as imaging agents — play a vital role in epidural procedures because they help providers “see” where a needle is being placed. Even a minor mistake could lead to permanent damage to the spinal cord.

Australian health officials said last week the supply of imaging agents was improving, but that normal supplies are “not likely to resume before the end of 2022.” They urged providers to continue conserving contrast agents and to postpone imaging that was not urgent.

Waiting and Wanting to Die in Canada

By Ann Marie Gaudon, PNN Columnist

RIP Margaret Bristow October 23, 1959 – August 10, 2022

No, that’s not a typo. My friend Maggie will be dying in a few days, on August 10 to be exact.

Confused? I am trying to make sense of this, too.

One night a few months ago, I was hurting. Oh, my goodness was I hurting! I was lying in bed and decided to do a quick body scan.

I began with my head. I had a throbbing headache, which I suspect was a result of fairly severe TMJ. It felt like my jaw was locked solid, which is terrifically painful, and my tongue was burning as well.

I also was suffering with tinnitus that night, which is typically accompanied by severe ear pain. I also felt gastroesophageal reflux burning a fiery hole in my gut.

Next up was a severe back injury from 2017, which was irritated and oh boy did that ever hurt! Down I went to my bladder, which was burning from an interstitial cystitis flare. Pudendal neuralgia had nerve pain radiating from my sacrum down both legs and into both hips. Osteoarthritis had my hips, knees, legs and ankles throbbing.

Finally, both feet felt like I had knives stabbing into them over and over, as I now have plantar fasciitis to add to my list of pain conditions. What a state I was in. Neuropathic pain, visceral pain, and musculoskeletal pain -- all in a rage.

Nine different pains in total that night, which is not at all typical for me. I had nowhere to put this earthly body for more comfort. Sitting or lying on my back increased the pudendal neuralgia; lying on my side increased my ear and hip pain; lying on my stomach was painful for my neck; and standing increased the plantar fasciitis.

I had nowhere to go, so I lay there quite still. In case you are wondering, yes, I have medications and I took them all. I also took everything OTC that I had in the house. It didn’t seem to make any difference; the pain was surging and the medications were no match for it.

I thought to myself that if this were to become permanent, I would surely not survive it. My problem-solving brain told me the only way out would be the release of death. If nothing could tame all of these pains, what choice would I have? I couldn’t work like this and I couldn’t engage in relationships like this.  I could barely string together two sentences in my head.

I could not function in any capacity, so I lay there quite still, trying my best to be with the pain, but not overtaken by it. In that one horrible night, I understood why my sweet friend had chosen to die on August 10, 2022.

‘I Would Rather Have My Medication Back’

Maggie Bristow has been in chronic pain for over 25 years from fibromyalgia, degenerative disc disease, spinal stenosis and arthritis. Her pain became so severe that she was given opiate medication, which she took for many years. By 2016, the Ottawa woman felt the medication was not working very well, because her pain was increasing.

Already feeling pressured to reduce his prescribing, her pain physician took her off opiates and tried many other types of treatment, but nothing worked. He told her there was nothing else left to try.

To this day I do not fully understand this part of Maggie’s story. Was she properly titrated on opiate medications? Were they combined with something else? What about novel approaches like opiates placed in the spinal fluid? I will never know. I do know that Maggie felt she was out of options.

“My body constantly feels like a blow torch has been taken to it. I’ve not been able to sleep in a horizontal position for 20 years and I am housebound due to the intense pain,” Maggie told me.

“Simple tasks like opening the mail, preparing food and maintaining good hygiene are agonizing, monumental tasks. I would rather have my medication back or be allowed to die peacefully.”

With her pain increasing, Maggie just wanted it to stop. That year she applied for assisted death under Canada’s Medical Assistance in Dying law (MAID), and was flatly denied because she did not meet the criterion that a natural death be “reasonably foreseeable."

MAGGIE AND HER LATE PARTNER, BRIAN

Maggie persevered and once again in 2019 applied for MAID. For the second time, she received a phone call telling her that her request had been denied. She felt very deflated, upset and confused.

Quality of life continued to worsen for Maggie and she waited patiently for new legislation to pass last year amending the MAID law, which removed the criterion that “death was foreseeable.”

When she applied for a third time, the MAID physician requested a new MRI, a second opinion from another neurologist, and someone to give her opiate pain medication. Maggie was dumbfounded at this third request, because she was searching for five years for opiates to no avail. She chose to ignore that, and responded to the other two requests which showed results that her spine was “totally inoperable.”

Weeks and months dragged on for Maggie. Finally, a call came from her general practitioner who told her that the MAID physician advised that she tried to contact Maggie with no success. Maggie said that was nonsense because she is housebound and never heard from her. The truth was that the MAID physician was not comfortable signing off on her case.

Part of the policy for MAID is that if a doctor is unwilling to help you, they must refer you to another doctor who will provide service for you. This however did not happen. Maggie was left hanging and extremely put out for all the time wasted when she could have been researching other avenues. She was now desperate.

A phone call took place to provincial MAID, with Maggie telling them that the Ottawa MAID declined her request. What were her options? They told her they would just refer her back to Ottawa. Really? Maggie was now quite angry and she called her GP, who reached someone else in the organization and found a MAID physician in Toronto who would help her to die.

This is where I go off the rails. A doctor will not help you get opiate medication, but will help you die? This was not the Canada that I was born into.

The MAID physician in Toronto reached Maggie via video conference and after her assessment said she would sign off immediately on her request. Maggie felt good about this but also knew that it takes two doctors to sign off for your peaceful death to happen.

Time dragged on again. The GP called her contact to ask what was happening and soon another video conference with a second MAID physician took place. This physician did not give Maggie any indication of what the decision was. Weeks later, Maggie received a call from the first doctor, who told her that her application was approved.

They would indeed help her to die as per her wishes, on August 10, 2022 at approximately 2:00 pm. They will have a long drive to get there, but Maggie’s sister will be with her. Afterwards, her organs will be harvested for donation and her body will be shipped back to Ottawa for cremation.   

Maggie blames Health Canada for the many problems she and other Canadian patients in severe pain have getting opiate medication.

“People like me, and there are many of us, continue to suffer. Suicide is our only option. This is a level of cruelty that is very difficult to fathom and really has to stop,” she said.

The world will be losing a gem on August 10. Maggie is a warrior woman for all that she has endured. She is a survivor through and through. I have seen grace, generosity of spirit, love, and even a sense of humor through all of this.

Is Maggie beyond treatment without a doubt? I will wonder about that for the rest of my life as I remember my sweet friend and all that she embodied.

Maggie’s partner Brian, the love of her life, passed in 2008. She will be survived by two children and five grandchildren.

Ann Marie Gaudon is a registered social worker and psychotherapist in the Waterloo region of Ontario, Canada with a specialty in chronic pain management.  She has been a chronic pain patient for over 30 years and works part-time as her health allows. For more information about Ann Marie's counseling services, visit her website. 

If you are in crisis and live in Canada, help is available by calling the Canada Suicide Prevention Service at 833-456-4566. If you live in the US, help is available by calling the 988 Suicide & Crisis Lifeline (formerly know as the National Suicide Prevention Lifeline) at 988 or 1-800-273-8255 (TALK). You can also call 911 for immediate help.

California Medical Board Urged to End Bias Against Rx Opioids

By Pat Anson, PNN Editor

The Medical Board of California got an earful from doctors, patients and their advocates during a public hearing Thursday on proposed changes to the board’s guideline for prescribing opioids and other controlled substances. Most speakers praised changes to the guideline that give physicians more flexibility in prescribing higher doses of opioids, but said they don’t go far enough.

“It continues to reflect pervasive bias that we find just about everywhere against the use of opioid pain medication,” said Kristen Ogden of Families for Intractable Pain Relief, a patient advocacy group. “There seems to be an underlying assumption that opioids are bad. Risks vs. benefit is often mentioned, but potential benefits receive very little attention in the draft. It’s kind of like a form of subliminal messaging.”

The board’s draft proposal continues to maintain that opioids “should not be the first line of treatment” for patients with chronic non-cancer pain and recommends that physicians “use extra precautions” when increasing doses above 50 morphine milligram equivalents (MME). Urine drug tests and pill counts are also strongly recommended for patients on long-term opioid therapy. Forced or rapid tapering of patients is discouraged, and doctors are urged to give patients at least 30 days’ notice before discharging them.   

“Opioid prescribing has been a major hot button issue for several years,” said board member Richard Thorp, MD, former president of the California Medical Association. “Our concern primarily is patient safety, and part of that patient safety is being able to prescribe to those patients that critically need these medications (in) a safe and viable environment.”

Thorp headed a task force that reviewed the medical board’s policies, which like many others around the country are modeled after the CDC’s 2016 opioid guideline.

“Unfortunately, many agencies, health plans and other kinds of oversight agencies took the guidelines as very strict guidelines,” said Thorp. “As result, many people who were on larger doses of opioid medications for chronic conditions that were intractable were significantly disadvantaged. Maybe that’s an extreme understatement. Many of them were really harmed by rapid tapering off of medications. Many primary care physicians, in particular, on which this burden had fallen basically backed out of the arena in prescribing chronic narcotics.”

The CDC has acknowledged the harm its opioid guideline has caused, but has been slow in revising it. An updated guideline is not expected to be finalized until late this year, nearly seven years after the original guideline was released.

‘It Has Killed People’

The medical board heard from several patients and physicians who are critical of its past efforts to rein in opioid prescribing, such as the board’s controversial “Death Certificate Project,” which resulted in hundreds of letters threatening disciplinary action being sent to doctors who prescribed opioids to patients who later overdosed. A study found that overdose deaths doubled in California after the project was launched, with many of the deaths linked to street drugs, not prescription opioids.

“It has killed people. My son is one of those people,” said Rosie Arthur, who said her son was abruptly taken off opioids after 24 years and put on antidepressants, which led to his death. “I don’t want to see anybody else die needlessly.”

Doctors told the board its enforcement efforts have had a chilling effect on pain management across the state.

“Some of our physicians are under investigation for compliance with these guidelines, which are resulting in serious unintended consequences,” said Lee Snook, Jr., MD, a pain management specialist in Sacramento. “Our physicians specializing in pain management have stopped taking new referrals, leaving patients and their primary physicians without local accessible options for complex pain management. One of these physicians announced his retirement last week.”   

“We have found it impossible to find pain consultants. There is nobody to refer our pain patients to, particularly patients who are on public programs. There is nobody in our community who will manage chronic medical pain,” said Aaron Roland, MD, a family physician in Burlingame. “Unfortunately, one of our clinicians recently had to leave us, leave our practice, because she had to devote herself full time to defending herself in a case brought by the Medical Board of California for opiate prescribing.”

“In the minds of our primary care docs, they really don’t want to have anything to do with any level of pain management for fear they will lose their license and lose their job,” said Michael Conroy, MD, chief medical officer for a large primary care practice in Sacramento. Conroy pointed out the board’s draft guideline uses the word “should” 44 times and the word “must” seven times.

“Very few of these statements are backed by much in the way of hard science,” he said. “The use of this language can be viewed as signaling an intent to use these statements to discipline doctors who aren’t perfect. Nobody is ever going to be perfect in documenting or attending to 51 separate things on a simple visit with a chronic pain patient.”

Conroy urged the board to modify its draft guideline to indicate that most of its recommendations are based on opinion and should not be used for disciplinary purposes or viewed as hard requirements.

Women Losing Access to Arthritis Drugs Due to Abortion Bans

By Pat Anson, PNN Editor

It didn’t take long for last month’s Supreme Court decision overturning Roe v. Wade to have a ripple effect on the U.S. healthcare system – including unintended consequences for women of childbearing age who have painful conditions such as lupus, rheumatoid arthritis, migraine and multiple sclerosis (MS).

Methotrexate and other drugs used to treat autoimmune and neurological conditions can also be used to induce abortions because they prevent cells from dividing. Although not commonly used for that purpose, methotrexate is officially listed in Texas as an “abortion-inducing drug” – an abortifacient -- putting practitioners at risk of running afoul of the state’s $10,000 bounty on anyone who helps a woman end a pregnancy after six weeks.

Even in states where abortion is legal, physicians, pharmacists and other healthcare providers have become cautious about prescribing or dispensing methotrexate.

“I received an email from my rheumatologist today that they are stopping all refills of methotrexate because it is considered an abortifacient,” a Virginia woman with lupus posted on Twitter just days after Roe was overturned. “If this is happening in a blue state with no trigger law, think of those in red states where abortion isn’t even legal. And those states that have trigger laws causing extreme and immediate loss of access.”

On the same day Roe was overturned, another poster on Twitter said his wife’s rheumatologist took all his female patients off medications that might cause a miscarriage

“So those patients are going to have to go off the drugs that were helping to control their condition and have worse health outcomes. People are going to die because of this,” he said.

The Lupus Foundation of America and Arthritis Foundation said they were aware of the situation and encouraged affected patients to contact them directly.

In an op/ed published in JAMA Neurology, neurologists at UC San Francisco School of Medicine warn the new abortion limits could have life-changing and life-threatening consequences for women with migraine, MS and epilepsy.

"Even if prescribed for a neurological condition, there are reports from patients across the country stating they are now unable to access methotrexate because it can also be used to induce abortion," wrote lead author Sara LaHue, MD, of the UCSF Department of Neurology. "This could increase risk of morbidity, mortality and irreversible disability accumulation for women with neurologic diseases."

Ironically, some treatments for neurological conditions also increase the likelihood of an unplanned pregnancy because they reduce the effectiveness of hormonal contraceptives. Physicians may become reluctant to prescribe those drugs to women of childbearing age.

Some neurologists may also rule out the use of monoclonal antibodies for women — not because they are used in abortions, but because they may harm a fetus.

"In many settings, women with MS are treated with less effective therapies, because these medications are perceived to be safer in pregnancy," said co-author Riley Bove, MD, of the UCSF Department of Neurology. "Often, neurologists are not familiar with how to time or optimize certain medications, or of their updated safety profile. The reversal of Roe v. Wade may reinforce decisions to stick with the less effective therapies, which may result in irreversible disability for some women with MS."

This week the Health and Human Services Department (HHS) warned retail pharmacies they are at risk of violating federal civil rights law if they deny women access to medications used in abortions. The warning specifically mentions methotrexate when its prescribed to someone with rheumatoid arthritis or some other disabling condition.

“If the pharmacy refuses to fill the individual’s prescription or does not stock methotrexate because of its alternate uses, it may be discriminating on the basis of disability,” HHS said..

Federal Judge Rejects Opioid ‘Public Nuisance’ Claims

By Pat Anson, PNN Editor

A federal judge in West Virginia has ruled that three major drug distributors did not fuel the opioid epidemic by shipping excessive amounts of opioid pain medication to pharmacies in Cabell County and the City of Huntington. According to one estimate, about 10% of people in the county are addicted to opioids.

“The opioid crisis has taken a considerable toll on the citizens of Cabell County and the City of Huntington. And while there is a natural tendency to assign blame in such cases, they must be decided not based on sympathy, but on the facts and the law,” Judge David Faber wrote in his 184-page ruling, which rejected claims that AmerisourceBergen, Cardinal Health and McKesson State acted in a way that made them a “public nuisance” under state law.

“To apply the law of public nuisance to the sale, marketing and distribution of products would invite litigation against any product with a known risk of harm, regardless of the benefits conferred on the public from proper use of the product,” the judge said. “The economic harm and social costs associated with these new causes of action are difficult to measure but would obviously be extensive. If suits of this nature were permitted any product that involves a risk of harm would be open to suit under a public nuisance theory regardless of whether the product were misused or mishandled.”

Judge Faber is the first federal judge to reject public nuisance claims in opioid litigation. State judges in California and Oklahoma made similar rulings last year.

The three drug distributors had previously agreed to multi-billion dollar settlements with dozens of states, but Cabell County chose not to be a part of those agreements, as did other counties in West Virginia, which has long been considered “ground zero” of the opioid epidemic.

“This case was always about holding these distributors accountable and providing our doctors, nurses, counselors, first responders and social workers with some of the resources needed to combat the opioid crisis. These companies were part of a powerful industry responsible for fueling the epidemic here in Huntington and across the country,” Huntington Mayor Steve Williams said in a statement.

Judge Faber acknowledged that prescription opioids were a “significant cause of drug overdose deaths” in Huntington and Cabell County. But he said the city and county failed to prove that drug distributors acted unlawfully or that the amount of opioids they shipped to pharmacies was unreasonable.

The three companies supplied retail pharmacies in Cabell County with over 51 million hydrocodone and oxycodone pills over an eight-year period. That works out to 67 pills annually for every man, woman and child in the county. It would be a month’s supply for a typical chronic pain patient, who might be prescribed 2 to 3 pills a day, depending on the dose and type of opioid.

“The volume of prescription opioids in Cabell/Huntington was determined by the good faith prescribing decisions of doctors in accordance with established medical standards,” Faber said. “Defendants shipped prescription opioid pills to licensed pharmacies so patients could access the medication they were prescribed.”

Public Health Problems   

Judge Faber also pointed out the poor state of public health in West Virginia, which has high rates of disability, arthritis, cancer, obesity and other health conditions that contribute to pain.

“The West Virginia population is relatively older and has relatively higher levels of obesity as well as a higher than average number of disabled persons, all of which tend to generate more needs for pain treatment,” Faber wrote. “Manual and physical labor is a significant component of the West Virginia economy and tends to generate more needs for pain treatment.”

In 2018, West Virginia became one of the first states in the country to impose hard limits on opioid prescribing, limiting first-time opioid prescriptions to 7 days’ supply and requiring refilled opioid prescriptions to be limited to 30 days’ supply.  

Sixty-four weeks after the law was adopted, opioid prescriptions overall dropped by 22% in West Virginia, similar to how prescribing trends have changed nationally.  The reduced prescribing, however, has failed to reduce drug overdoses, which have risen to record levels.

According to a new CDC database, West Virginia has the second highest overdose rate in the country and leads the nation in drug deaths involving illicit fentanyl, prescription opioids, stimulants and methamphetamine. In 2020, only 5.2% of the overdose deaths in West Virginia involved a patient being treated for pain.   

Another Look at the Opioid Risk Tool

By Dr. Lynn Webster

I'm a proud grandfather to two young granddaughters. They are my world. Watching the U.S. Supreme Court rescind women's right to decide what to do with their own bodies made me feel angry that my granddaughters will be subjected to dehumanizing discrimination.

This tyranny against women extends beyond the Supreme Court’s decision over Roe vs. Wade.

I have read multiple accounts of women who are being denied access to opioid medication because they acknowledge a history of toxic adverse experiences as children or adolescents. Many such instances have occurred after women completed the Opioid Risk Tool, a questionnaire that asks a person if they have a history of preadolescent sexual abuse.

The refusal to prescribe opioids to women with a history of preadolescent sexual abuse is a defensive measure by providers to avoid being accused of causing an Opioid Use Disorder (OUD).

Why I Developed the Opioid Risk Tool

The Opioid Risk Tool (ORT) that I developed more than 20 years ago was designed to assess the risk of someone who was prescribed opioids for chronic pain treatment showing aberrant drug-related behavior.

The ORT was a simple questionnaire that could be administered and scored in less than a minute. It was developed at a time when we had no way to assess the risk of developing opioid abuse in patients who were prescribed an opioid for non-cancer pain. We needed a tool to help evaluate whether the risk of potential harm from opioids outweighed the potential good for each individual.

I never intended for doctors to use the ORT to determine who should or shouldn’t be prescribed an opioid. My goal was to help doctors identify patients who might require more careful observation during treatment, not to deny the person access to opioids.

Since abuse and addiction are diagnosed by observing atypical behaviors, knowing which patients are at greatest risk for displaying those behaviors is useful in establishing appropriate levels of monitoring for abuse. This was intended to protect the patient from potential harm. It was never supposed to be used as an excuse to mistreat patients.

The original version of the ORT contained 10 questions, including whether a patient had a history of preadolescent sexual abuse. Women who answered "yes" scored 3 points; while men who responded affirmatively scored 0 points. The higher you scored, the more closely your doctor would need to monitor your opioid use during your treatment.

The ORT questionnaire was based on the best evidence at the time. Multiple studies have since confirmed the validity of the questions used in the questionnaire. However, many people have criticized the question that asks about a history of preadolescent sexual abuse because of a perceived gender inequity. In addition, some doctors have generalized the ORT's question about preadolescent trauma so that it applies to a history of female sexual abuse at all ages.

I have written that the ORT has been weaponized by doctors who are looking for a reason to deny patients -- particularly, women -- adequate pain medication.

There are doctors who use their power to determine whether to treat a woman's chronic pain with an opioid or allow her to suffer needlessly based on the ORT's answers. This is no less malevolent than a forced taper resulting in suicides or the use of the CDC opioid prescribing guideline to criminally charge providers for not following the CDC's recommendation. In all of these situations, an injustice is being committed against innocent people.

It is also not much different from the Supreme Court’s decision to ignore a woman’s right to access full reproductive rights. Both are attacks on women.

Fortunately, Martin Cheatle, PhD, and his team published a revised Opioid Risk Tool in the July 2019 edition of the Journal of Pain. In his research, Dr. Cheatle found that a revised ORT using 9 questions instead of 10 was as accurate as, if not better than, the original ORT in weighing the risk of patients for OUD. The revised ORT eliminates the use of a woman's sexual abuse history as a risk factor.

At a time when females have had their human rights taken away by a Supreme Court vote, it is especially appropriate to reconsider how we assess risks for potential opioid abuse for women.

It distresses me to know that, while the original ORT served to help assess the risk opioids posed for individuals, it has also caused harm. Since the question about a woman's sexual abuse history does not provide any additional benefit, there is no reason to retain it. The revised ORT should be used instead of the original ORT.

Lynn R. Webster, MD, is Senior Fellow at the Center for U.S. Policy (CUSP) and Chief Medical Officer of PainScript. He also consults with the pharamaceutical industry.

Lynn is the author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. You can find him on Twitter: @LynnRWebsterMD.

What’s Missing in ‘Elvis’ Movie: The King’s Chronic Illness

By Pat Anson, PNN Editor

There’s a scene towards the end of the new “Elvis” movie when you know the end is coming soon. Presley, as depicted by actor Austin Butler, collapses in a hallway minutes before being scheduled to take the stage at the International Hotel in Las Vegas.

Instead of rushing an unconscious Elvis to a hospital, manager Tom Parker --- played by a surprisingly villainous Tom Hanks -- declares that the show must go on and summons “Dr. Nick” to make it right. After a quick injection of stimulant drugs, Elvis recovers just enough to sing, dance and entertain an adoring crowd in a packed showroom.   

That one scene sums up how the real Elvis Presley spent his final years before dying of an apparent heart attack in 1977 at the young age of 42. Popping pills. Slurring his words. Deeply depressed. And driven to continue performing by “Colonel” Parker and others.

“They really tried to push Elvis beyond his capacity in the last few years of his life. He was disabled,” says Dr. Forest Tennant, a retired physician and pain management expert who is one of the last people alive to be intimately familiar with Elvis’ drug use and medical problems.

In 1981, Tennant was hired by an attorney for Dr. George Nichopoulos (Dr. Nick), who faced criminal charges in Presley’s death. Tennant reviewed the autopsy report, medical records and a confidential 161-page private investigation, and testified as a defense witness for Nichopoulos, who would be acquitted of charges of overprescribing drugs.

After the trial, Tennant remained curious about Elvis’ medical problems and continued his research while treating people with intractable pain. The knowledge and experience Tennant gained in the last 50 years led to his recent book, appropriately titled “The Strange Medical Saga of Elvis Presley.”  

Elvis did indeed suffer from heart problems aggravated by an excessive use of drugs, but Tennant believes the ultimate cause of his death was a connective tissue disorder called Ehlers-Danlos syndrome (EDS), a major cause of intractable pain and other chronic health problems.

A diagnostic screening tool for EDS didn’t exist when Elvis was alive and few physicians were even aware of the condition. But Tennant thinks Presley had all the symptoms of EDS, including an unusual degree of flexibility and double jointness that allowed him to swing his hips and gyrate wildly. Those sexy dance moves helped make Elvis famous, but they also foretold what lay in store for him.

“EDS is a genetic connective tissue collagen disorder, and what that means is that you are genetically predetermined to have your collagen in certain tissues either disappear or deteriorate or become defective, and to put it bluntly, you can have a rectal problem and an eye problem at the same time due to the same cause because your collagen is deteriorating in these tissues,” Tennant told my colleague Donna Gregory Burch in a 2021 interview. “If you get a severe case like Elvis Presley, your life is going to be very miserable, and you're going to die young unless you get vigorous treatments.”      

The day before he died, a dentist gave Presley codeine for an aching tooth, not realizing how sick he was or that codeine could cause his heart to stop. Elvis collapsed in the bathroom 24 hours later. His sudden death led to rumors that he died from an overdose or even a horrible case of constipation. The truth is more complex.

“Nothing happened to Elvis Presley that we don't have a good logical, scientific explanation for now. But certainly back in those days we didn't,” Tennant explained. “Elvis Presley had multiple diseases. He was terribly ill, and he died accidentally in some ways with a dentist giving him codeine for his bad tooth, and his bad teeth were also part of the same disease that gave him a bad colon and a bad eye and a bad liver. They were all connected.

“He had all these metabolic defects due to his genetics, and so the codeine built up in his system. He had this terrible heart, so he died suddenly, within seconds, as he was trying to sit on the commode.”

Fortunately, the “Elvis” movie spares us any final scenes like that – ending instead with actual clips from one of Presley’s last concerts. They show a tired and very sick man, aged beyond his years and sweating profusely. But he still sang like “The King.”

All proceeds from sales of “The Strange Medical Saga of Elvis Presley” go the Tennant Foundation, which gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.

Supreme Court Rules in Favor of Doctors Appealing Opioid Convictions

By Pat Anson, PNN Editor

In a precedent setting case, the U.S. Supreme Court has ruled in favor of two doctors who were convicted of prescribing high doses of opioid pain medication outside the usual standard of medical care. The ruling could potentially impact dozens of past and future cases in which doctors are accused of “overprescribing” opioids to their patients.

In their combined appeals, lawyers for Dr. Xiulu Ruan and Dr. Shakeel Kahn argued that jurors were not properly instructed that doctors are allowed to prescribe opioids under the Controlled Substances Act (CSA), as long as they act in good faith and with a medical purpose.

Unlike recent rulings which saw the high court bitterly divided over abortion and gun control, the justices ruled unanimously 9 to 0 in favor of the doctors, with some quibbling over the legal reasons.

Writing for the majority, Justice Stephen Breyer said government prosecutors failed to “prove beyond a reasonable doubt that the defendant knowingly or intentionally acted in an unauthorized manner" under the CSA.

In a concurring opinion, Justice Samuel Alito drew a finer line, saying doctors could still be prosecuted under the CSA if they knowingly acted in a way “foreign to medicine — such as facilitating addiction or recreational drug abuse.”

The high court’s ruling does not overturn the convictions of Ruan and Kahn. Instead, the cases are remanded back to lower courts for review, where charges against the doctors could be dismissed or new trials ordered.

‘Monumental Decision’

Pain patients and their advocates cheered the high court ruling, saying it could have a sweeping impact on pain management in the United States. Fearing prosecution by the DEA or state medical boards, many doctors have stopped prescribing opioids, tapered patients to lower doses, or simply stopped treating pain.  

“This is a monumental decision that will literally save lives because fewer patients will be abandoned by their doctors for fear of losing their freedom,” said Lynn Webster, MD, a Senior Fellow at the Center for U.S. Policy (CUSP) and Chief Medical Officer of PainScript.  “Physicians have been afraid to prescribe controlled substances even with an appropriate indication for fear of a government expert testifying they believe it is not the standard of care.  

“The Court’s decision will affect not only Ruan and all healthcare professionals with authority to prescribe any controlled substances, but millions of patients now and in the decades to come.”  

"I would say (the ruling) directly challenges many past convictions of doctors that were tainted by improper instructions to juries or anti-opioid biases by judges,” said patient advocate Red Lawhern, PhD. “It may also make future convictions more difficult given that the decision forces DEA and other law enforcement authorities to demonstrate beyond reasonable doubt that prescribers knew their practices exceeded accepted medical standards." 

“There remain other issues to be decided, but this decision was the right one for pain physicians and patients.  It affirmed the higher standard for the government to prove doctors acted with criminal intent,” said Kristen Ogden, a patient advocate and caregiver for her husband, who is disabled by intractable pain.

Complicating the cases of Ruan and Kahn is that they were both convicted of crimes outside of the CSA.

Ruan, who practiced in Alabama, prescribed Subsys to many of his patients, an expensive and potent fentanyl spray that was only approved by the FDA for breakthrough cancer pain. Ruan was also convicted of taking kickbacks from Insys Therapeutics, the maker of Subsys. He was sentenced to 21 years in prison.    

Kahn, who practiced in Wyoming and Arizona, was convicted of prescribing excessive amounts of oxycodone and running a criminal enterprise that resulted in the death of a patient. He is serving a sentence of 25 years.

Why Some Drugs Work Better on Different Types of Pain

By Dr. Rebecca Seal and Dr. Benedict Alder

Without the ability to feel pain, life is more dangerous. To avoid injury, pain tells us to use a hammer more gently, wait for the soup to cool or put on gloves in a snowball fight. Those with rare inherited disorders that leave them without the ability to feel pain are unable to protect themselves from environmental threats, leading to broken bones, damaged skin, infections and ultimately a shorter life span.

In these contexts, pain is much more than a sensation: It is a protective call to action. But pain that is too intense or long-lasting can be debilitating. So how does modern medicine soften the call?

As a neurobiologist and an anesthesiologist who study pain, this is a question we and other researchers have tried to answer. Science’s understanding of how the body senses tissue damage and perceives it as pain has progressed tremendously over the past several years. It has become clear that there are multiple pathways that signal tissue damage to the brain and sound the pain alarm bell.

Interestingly, while the brain uses different pain signaling pathways depending on the type of damage, there is also redundancy to these pathways. Even more intriguing, these neural pathways morph and amplify signals in the case of chronic pain and pain caused by conditions affecting nerves themselves, even though the protective function of pain is no longer needed.

Painkillers work by tackling different parts of these pathways. Not every painkiller works for every type of pain, however. Because of the multitude and redundancy of pain pathways, a perfect painkiller is elusive. But in the meantime, understanding how existing painkillers work helps medical providers and patients use them for the best results.

Anti-Inflammatories

A bruise, sprain or broken bone from an injury all lead to tissue inflammation, an immune response that can lead to swelling and redness as the body tries to heal. Specialized nerve cells in the area of the injury called nociceptors sense the inflammatory chemicals the body produces and send pain signals to the brain.

Common over-the-counter anti-inflammatory painkillers work by decreasing inflammation in the injured area. These are particularly useful for musculoskeletal injuries or other pain problems caused by inflammation such as arthritis.

Nonsteroidal anti-inflammatories like ibuprofen (Advil, Motrin), naproxen (Aleve) and aspirin do this by blocking an enzyme called COX that plays a key role in a biochemical cascade that produces inflammatory chemicals. Blocking the cascade decreases the amount of inflammatory chemicals, and thereby reduces the pain signals sent to the brain.

While acetaminophen (Tylenol), also known as paracetamol, doesn’t reduce inflammation as NSAIDs do, it also inhibits COX enzymes and has similar pain-reducing effects. Prescription anti-inflammatory painkillers include other COX inhibitors, corticosteroids and, more recently, drugs that target and inactivate the inflammatory chemicals themselves. Aspirin and ibuprofen work by blocking the COX enzymes that play a key role in pain-causing processes.

Because inflammatory chemicals are involved in other important physiological functions beyond just sounding the pain alarm, medications that block them will have side effects and potential health risks, including irritating the stomach lining and affecting kidney function. Over-the-counter medications are generally safe if the directions on the bottle are followed strictly.

Corticosteroids like prednisone block the inflammatory cascade early on in the process, which is probably why they are so potent in reducing inflammation. However, because all the chemicals in the cascade are present in nearly every organ system, long-term use of steroids can pose many health risks that need to be discussed with a physician before starting a treatment plan.

Topical Medications

Many topical medications target nociceptors, the specialized nerves that detect tissue damage. Local anesthetics, like lidocaine, prevent these nerves from sending electrical signals to the brain.

The protein sensors on the tips of other sensory neurons in the skin are also targets for topical painkillers. Activating these proteins can elicit particular sensations that can lessen the pain by reducing the activity of the damage-sensing nerves, like the cooling sensation of menthol or the burning sensation of capsaicin.

Because these topical medications work on the tiny nerves in the skin, they are best used for pain directly affecting the skin. For example, a shingles infection can damage the nerves in the skin, causing them to become overactive and send persistent pain signals to the brain. Silencing those nerves with topical lidocaine or an overwhelming dose of capsaicin can reduce these pain signals.

Nerve Injury Medications

Nerve injuries, most commonly from arthritis and diabetes, can cause the pain-sensing part of the nervous system to become overactive. These injuries sound the pain alarm even in the absence of tissue damage. The best painkillers in these conditions are those that dampen that alarm.

Antiepileptic drugs, such as gabapentin (Neurontin), suppress the pain-sensing system by blocking electrical signaling in the nerves. However, gabapentin can also reduce nerve activity in other parts of the nervous system, potentially leading to sleepiness and confusion.

Antidepressants, such as duloxetine and nortriptyline, are thought to work by increasing certain neurotransmitters in the spinal cord and brain involved in regulating pain pathways. But they may also alter chemical signaling in the gastrointestinal tract, leading to an upset stomach.

All these medications are prescribed by doctors.

Opioids

Opioids are chemicals found or derived from the opium poppy. One of the earliest opioids, morphine, was purified in the 1800s. Since then, medical use of opioids has expanded to include many natural and synthetic derivatives of morphine with varying potency and duration. Some common examples include codeine, tramadol, hydrocodone, oxycodone, buprenorphine and fentanyl.

Opioids decrease pain by activating the body’s endorphin system. Endorphins are a type of opioid your body naturally produces that decreases incoming signals of injury and produces feelings of euphoria – the so-called “runner’s high.” Opioids simulate the effects of endorphins by acting on similar targets in the body.

While opioids can provide strong pain relief, they are not meant for long-term use because they are addictive.

Although opioids can decrease some types of acute pain, such as after surgery, musculoskeletal injuries like a broken leg or cancer pain, they are often ineffective for neuropathic injuries and chronic pain.

Because the body uses opioid receptors in other organ systems like the gastrointestinal tract and the lungs, side effects and risks include constipation and potentially fatal suppression of breathing. Prolonged use of opioids may also lead to tolerance, where more drug is required to get the same painkilling effect. This is why opioids can be addictive and are not intended for long-term use. All opioids are controlled substances and are carefully prescribed by doctors because of these side effects and risks.

Cannabinoids

Although cannabis has received a lot of attention for its potential medical uses, there isn’t sufficient evidence available to conclude that it can effectively treat pain. Since the use of cannabis is illegal at the federal level in the U.S., high-quality clinical research funded by the federal government has been lacking.

Researchers do know that the body naturally produces endocannabinoids, a form of the chemicals in cannabis, to decrease pain perception. Cannabinoids may also reduce inflammation. Given the lack of strong clinical evidence, physicians typically don’t recommend them over FDA-approved medications.

Matching Pain to Drug

While sounding the pain alarm is important for survival, dampening the klaxon when it’s too loud or unhelpful is sometimes necessary.

No existing medication can perfectly treat pain. Matching specific types of pain to drugs that target specific pathways can improve pain relief, but even then, medications can fail to work even for people with the same condition. More research that deepens the medical field’s understanding of the pain pathways and targets in the body can help lead to more effective treatments and improved pain management.

Rebecca Seal, PhD, is an Associate Professor of Neurobiology at University of Pittsburgh Health Sciences. Benedict Alter, MD, is an Assistant Professor of Anesthesiology and Perioperative Medicine, at University of Pittsburgh Health Sciences.

This article originally appeared in The Conservation and is republished with permission.

Overdose Crisis Projected to Grow Worse in Canada

By Pat Anson, PNN Editor

Opioid-related deaths reached a record level in Canada last year and are likely to continue rising in 2022, according to a grim new report from the Public Health Agency of Canada (PHAC).

The report estimates that 7,560 people died from opioid-related overdoses in 2021, and projects that number is likely to be surpassed this year. On average, there were 21 drug deaths daily in Canada in 2021, up from eight deaths only five years earlier.

The vast majority of the deaths were linked to illicit fentanyl, a potent synthetic opioid that was often combined with other substances. Men accounted for 74% of the deaths, most them between 20 and 59 years of age.

“For many years, Canada has seen a significant rise in opioid and other substance-related deaths and harms, and this crisis continued to worsen over the course of 2021, in the midst of the COVID-19 pandemic,” Drs. Theresa Tam and Jennifer Russell, co-chairs of a PHAC Special Advisory Committee on Opioid Overdoses, said in a joint statement.

“Additionally, the vast majority of opioid-related deaths continue to be accidental, and more than half also involved the use of a stimulant (e.g., cocaine, methamphetamine), underscoring the polysubstance nature of the overdose crisis.”

Notably, only 19 percent of the deaths involved opioids manufactured by a pharmaceutical company, although the data is not broken to determine if they were bought, stolen or obtained legally through a prescription.    

The latest updated modelling projections from PHAC suggest that opioid-related deaths in Canada are likely to remain high or even increase over the next six months. Under four different scenarios, researchers think the most likely one is “Scenario 2,” in which the level of fentanyl in the drug supply remains the same, contributing to about 4,000 more deaths in the last half of 2022.

Estimated Opioid-Related Deaths in Canada

Public Health Agency of Canada

“The data contained in this release underscore the seriousness of substance-related harms in Canada, and the urgent need to take further action to help prevent them. This includes the critical need to expand access to high quality, evidence-based and innovative care to support people who use drugs,” Tam and Russell said.

Canada recently announced an experimental program that will decriminalize drug possession in British Columbia, the province hardest hit by the overdose crisis. It has also allowed the creation of safe injection sites and made heroin available by prescription.

Like Canada, the U.S. saw a record number of overdoses last year, with nearly 108,000 drug deaths. Researchers at the University of Pittsburgh say overdoses are doubling every 10 years, fueled by multiple drugs, socioeconomic inequality and social isolation.

"There are theories, but nobody has an explanation for why drug overdose deaths so consistently stick to this exponential growth pattern,” said Hawre Jalal, MD, a former professor at Pitt Public Health who is now at the University of Ottawa. "Five years ago, leaders in the drug addiction and policy fields called our findings a coincidence. We need to stop denying that this exponential growth will continue if we don't get at the root causes and fix them."