Overdose Deaths Double for Teenagers Amid Fentanyl Surge

By Pat Anson, PNN Editor

Drug deaths among U.S. teenagers have risen sharply in the last two years, according to a new study that found the number of fatal overdoses doubled for adolescents aged 14 to 18 years.

In 2019, there were 492 drug deaths among adolescents. In 2021, there were an estimated 1,146 fatal overdoses, a 133% increase.

The vast majority of adolescent drug deaths last year involved illicit fentanyl (77%), followed by benzodiazepines (13%), methamphetamines (10%) and cocaine (7%). Less than 6% of the overdoses among teens involved a prescription opioid.

The study findings, reported in the journal JAMA, reflect what is happening in the overall U.S. population, with drug overdoses rising to record levels. They also mark the reversal of a decade long trend of fewer overdose deaths among teens, which coincided with declining rates of illicit drug use.

Researchers say adolescents may be unaware or naive about the risks posed by fentanyl, a synthetic opioid up to 100 times more potent than morphine and 50 times stronger than heroin. In a prescription, fentanyl plays a valuable role in treating severe pain, but as a street drug it can be deadly

“Beginning in 2020, adolescents experienced a greater relative increase in overdose mortality than the overall population, attributable in large part to fatalities involving fentanyls,” lead author Joseph Friedman, MPH, University of California, Los Angeles, reported in the journal JAMA.

“In the context of decreasing adolescent drug use rates nationally, these shifts suggest heightened risk from illicit fentanyls, which have variable and high potency. Since 2015, fentanyls have been increasingly added to counterfeit pills resembling prescription opioids, benzodiazepines, and other drugs, which adolescents may not identify as dangerous and which may be playing a key role in these shifts.”

U.S. Adolescent Overdose Deaths

SOURCE: jama

Friedman and his colleagues found the highest overdose rates among Native American, Alaska Native and Latino adolescents, reflecting what they called a “wider pattern of increasing racial and ethnic inequalities” in drug deaths.

Fentanyl is even killing kids who have not reached their teenage years. In California, a boy was recently arrested and charged with murder in the death of 12-year-old Dalilah Guerrero. The 16-year-old suspect allegedly sold a counterfeit pill made with fentanyl to the girl, who overdosed after crushing and snorting the tablet at a party in San Jose.

The spike in adolescent drug deaths comes even as substance abuse by teens fell to record lows. An annual survey by the University of Michigan found significant declines in all types of drug use by adolescents in 2021, with the use of prescription opioids falling to the lowest level in nearly two decades.    

DEA Warns of Fentanyl Mass Overdoses

Public health experts and law enforcement agencies are growing increasingly alarmed by the rising number of fentanyl overdoses. Last week, the DEA warned of a nationwide spike in fentanyl-related mass overdose events, in which three or more overdoses occur in the same location.

In the past three months, at least seven mass overdoses were reported in Florida, Texas, Colorado, Nebraska, Missouri and Washington, DC, resulting in 29 deaths. Three people died in a hotel room in Cortez, Colorado after ingesting what that they thought were 30mg oxycodone pills, but were actually counterfeit pills containing fentanyl.

“Tragic events like these are being driven by fentanyl. Fentanyl is highly-addictive, found in all 50 states, and drug traffickers are increasingly mixing it with other types of drugs — in powder and pill form — in an effort to drive addiction and attract repeat buyers,” DEA Administrator Anne Milgram said in a letter to federal, state and local law enforcement agencies. 

“We recommend that the members of your offices assume that all drugs encountered during enforcement activities now contain fentanyl. Given fentanyl’s extreme toxicity and the increases we are seeing in the distribution of polydrug substances containing fentanyl, please take all the precautions you would take when handling fentanyl whenever you interdict any illicit substance.”

A recent study by the National Institute of Drug Abuse estimated that over 9.6 million counterfeit pills containing fentanyl were seized by U.S. law enforcement agencies last year.

Deadline Nears for Public Comments on Revised CDC Opioid Guideline

By Pat Anson, PNN Editor

The public comment period on the revised draft of the CDC’s opioid prescribing guideline ends Monday, April 11th. So far, over 4,200 comments have been submitted in the Federal Register. You can leave a comment and read the ones already submitted by clicking here. A final revised guideline is not expected to be released by the CDC until late this year.

Like the original guideline, the revised version still maintains that opioids should not be used as a first line or routine therapy for pain, but takes a more flexible approach to dosing. Providers are urged to weigh the individual needs of each patient and not take a one-size-fits-all approach to pain care.

“It’s important to point out that the guideline is not final and the step that we’re at now is a real critical point in the process to wrestle with and get feedback,” Christopher Jones, PharmD, Acting Director of the CDC’s National Center for Injury Prevention and Control, told PNN in February.

“And that’s why it’s important that we hear from readers of Pain News Network to get feedback, to get that experience, so as we move toward a final guideline, we can incorporate that feedback. We hope that insurers, medical community, law enforcement and others will also review the guideline and provide feedback.”

Does 50 MME replace 90 MME?

Perhaps the most controversial change in the opioid guideline is the elimination of dose thresholds. The original guideline strongly encouraged providers not to exceed doses of 90 morphine milligram equivalents (MME) per day. That 90 MME limit has been dropped from the revised draft, but providers are still urged to be cautious about going over 50 MME because higher doses have “diminishing returns in benefits relative to risks.”

That change has led to significant confusion about what CDC is trying to do. Many patients are concerned that 50 MME will be seen as the new recommended limit, a dose they consider low for severe pain.

“Does the 50 MMEs replace the 90 MMEs? This is asking for more and more suicides. Much of the proposed guidelines are the same except you removed 90 MMEs and replaced it with 50 MMEs. Go back to the beginning and start over,” Pamela Hoard wrote in her comment.

“It is ridiculous to put a numerical number, such as 50 MME/day, to a risk/benefit outcome when there is no scientific evidence to support MME's,” wrote Joe Benotz, who said he was a pharmacist. “Using unvalidated MME to guide dosing opioid pain meds has in the past led to significant harms to pain patients. Continued use of MME numbers will cause more harm in the future.”

“I'm a doctor in Michigan who has lost his license because of the 90 MME requirement. It doesn't matter if you add caveats, prosecutors see a limit and it becomes the law. The 50 MME ‘suggestion’ is even worse,” wrote Jonathan Roberston.

The anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP) posted a letter in the Federal Register supporting many of the guideline changes, including the cautionary language about exceeding 50 MME. PROP continues to maintain that long-term use of opioids is too risky.

“Available evidence indicates modest benefits of opioids for acute pain relative to placebo, while benefits for chronic pain have not been shown,” PROP said. “New evidence also demonstrates significant risks of high dose opioids (>50 MME/day) and shows that alternatives to opioids often provide equal or superior benefit with a markedly better safety profile. These are important findings which PROP fully supports being widely disseminated to medical professionals and to the public.”

Medical Societies Weigh In

Other medical societies and physician groups generally support the guideline changes, but with important caveats. The American Society of Anesthesiologists (ASA) is concerned about the CDC making new recommendations for treating postoperative pain that are based on “inconsistent” evidence from a small number of clinical trials.

“The agency fails to recognize the complexities around the many different types of surgery that require different forms of pain control, especially that some patient populations may need more pain relief and different therapies than others,” the ASA said in a letter that basically told the CDC to stay in its lane.

“ASA recommends that the agency note in the updated Guideline that clinicians defer to professional medical society guidelines and standards of care for surgical procedures. Medical specialty societies, including ASA, are the experts in perioperative pain care, including postsurgical pain, and are best suited to develop clinical guidelines in this specific area.”

In a move apparently timed to preempt the CDC, the ASA recently joined the American Medical Association and 13 other medical societies in releasing new advice for managing postoperative pain in “complex patients,” such as those with chronic pain and those taking opioids prior to surgery. The societies said patients should be allowed to stay on opioids before, during and after surgery.

Other medical organizations urged the CDC to avoid the mistakes of the past, such as allowing insurers, states, regulators and law enforcement to adopt its voluntary recommendations as inflexible standards of practice.  

“It is imperative that the CDC assure the new guidelines emphasize not only support for safe, quality pain care, but also strive for clarity to prevent rigid application of the guidelines and prevent misunderstandings and misapplications that may result in substandard care and needless suffering by patients with unrelieved pain,” said Maureen Cooney, DNP, President of the American Society for Pain Management Nursing.

Other professional societies took offense that their particular specialties were omitted or only briefly covered in the revised guideline.

The American Society of Regional Anesthesia and Pain Medicine urged the CDC to include a “robust discussion” on the use of nerve blocks, epidural steroid injections and other interventional pain procedures.

The American Association of Neurological Surgeons said it was “disappointed” that the revised guideline “fails to adequately explore” implanted neuromodulation devices such as spinal cord stimulators.

And the American Psychological Association was offended by “the obvious, and unfortunate, omission of clinical hypnosis” from the guideline as an alternative pain therapy.

Study Finds Cannabis Oil Effective in 9 out of 10 Pain Patients

By Pat Anson, PNN Editor

Medical cannabis improved symptoms in 9 out of 10 chronic pain patients taking oral formulations of cannabidiol (CBD) and tetrahydrocannabinol (THC), according to a large new study in Colombia.

The observational study, the largest of its kind in Latin America, is the first clinical peer-reviewed evidence on the effectiveness and safety of cannabis products made by Khiron Life Sciences. Over 2,100 patients with a variety of chronic pain conditions self-reported their symptoms after taking CBD and THC oil-based formulations at a Khiron clinic in Bogota.

The findings are published in the peer-reviewed journal Frontiers in Pain Research.

"We believe these findings to be generalizable across patient populations, considering that our results are extremely well-aligned with those reported by researchers working with similar clinical populations in nations with long-standing medicinal cannabis access programs, such as Israel and Canada," lead author Guillermo Moreno-Sanz, Global Scientific Director of Khiron Life Sciences, said in a press release.

While most previous studies only looked at the short-term effects of cannabis ingested through a variety of different methods, this study focused on the safety and efficacy of cannabis oils for up to 26 weeks. Most participants were female, with an average age of 59 years.

Patients received cannabis oils composed primarily of CBD (30mg CBD/2mg THC) or a more balanced formulation (14mg CBD/12mg THC). 

Key findings in the study include:

• 92.5% of patients reported some degree of improvement in their chronic pain.

• 75% reported moderate or robust reduction in chronic pain

• 72% reported no adverse side effects

The degree of improvement was similar between both formulations, although males reported less effectiveness in the first 4 weeks of treatment.

Most side effects were mild, such as somnolence (13%), dizziness (8%) and dry mouth (4%), and faded away after 12 weeks of treatment. No serious adverse events requiring hospitalization or medical intervention were reported.

"This study, based on Khiron's medical products, is critical to reassure physicians and health insurance providers of the efficacy of medicinal cannabis to treat chronic pain. The global impact and economic burden of chronic pain in our society, mounting medical evidence will increase access to cannabinoid-based medicines worldwide." says Alvaro Torres, Khiron CEO and Director.

Khiron Life Sciences is a medical cannabis company based in Colombia. Its products are sold in Colombia, Peru, Germany, UK and Brazil, and will soon be available in Mexico.

Recent studies have also found cannabis oil effective in treating fibromyalgia and migraine.

Sacroiliac Joints: An Overlooked Cause of Back Pain

By Victoria Reed, PNN Columnist

I’ve suffered from low back pain for a long time, beginning in my 20’s. I would have terrible spasms, pain, stiffness and leg numbness, which left me unable to walk or function at all.

I went through the usual testing to determine the cause and was asked if I had had some kind of accident or injury. The answer was always no. The only thing I could think of that may have contributed to the back pain was the fact that I ran track throughout my elementary and high school years. I figured all that running might have taken a toll on my spine.

An MRI revealed a bulging disk at the lumbar level. I was offered a nerve block, which helped relieve the pain for a while. But when I had children, the pain returned -- probably because the strain and added weight from pregnancy put extra pressure on my spine. 

A doctor offered a series of epidural spinal injections in which a steroid would be injected to try and shrink the bulging disk. The first shot didn’t work at all, but I was encouraged to try another one. The second didn’t work either. I was then put on pain and nerve medications, which did help somewhat.

Because I was using a prescription opioid, I had to go back periodically for regular exams to see if the meds were helping and still necessary. During one of those routine exams, the doctor asked me to point specifically to where the pain was coming from. I had been doing my own research online and thought the majority of the pain wasn’t coming from the bulging disk, but from my sacroiliac (SI) joints.

The SI joints are made up of the sacrum and the ilium of your pelvis, and are located on the right and left sides of your lower back. They are held in place by strong ligaments. Rheumatoid arthritis (RA) might increase the risk of having trouble with these joints. Though it’s commonly said that RA primarily affects the hands and feet, any joint can be affected.

I mentioned that to my doctor, but he wanted me to have more epidural steroid injections. I refused, partly because they didn’t help before and partly because I’m diabetic, and high-dose steroids cause the blood sugar to go up.

From there, I was sent to physical therapy. The therapy sessions were centered around strengthening my core abdominal muscles, and they did help reduce the number of times my back went out. However, the SI joint pain was still consistently there. During subsequent doctor appointments, and finally after some convincing, the doctor agreed that the SI joints were causing my pain.

SI joint pain is an often-overlooked cause of back pain, and can be confused with disk pain. It’s important to find any and all causes of persistent back pain because the treatments can be different.

Some years later, I agreed to try steroid injections into the SI joints, despite the effect I knew it would have on my blood sugar. Steroids can also make your body resistant to insulin.  I figured it was worth the risk if there was a chance at pain reduction. However, I knew that it would not be something that I could do regularly, and while not 100% helpful, there was some temporary modest relief. 

Since then, I’ve been able to identify what triggers the SI joint pain, and I use several different modalities for relief, including ice, low-dose oral steroids, stretches, and prescription pain medication.

How to Tell the Difference

Pain that is from a bulging or herniated disk can radiate down one leg and cause numbness or tingling. This pain is usually centered in the lower back, whereas pain from the SI joints can be pinpointed to one side or both. Pain from a bad disk can travel all the way down to the feet or toes, while SI joint pain usually stays above the knee.

Leg weakness can be very severe in a disk rupture, even to the point where you are dragging your foot. If you lose bowel or bladder control, that may be a sign of a serious condition called cauda equina syndrome and is considered a medical emergency!

Weakness in a leg from SI joint dysfunction usually isn’t prominent, but you can have numbness and tingling. SI joint pain can be triggered by going from a sitting to a standing position or by sleeping on one side. A trip or a stumble can also set off SI joint pain, and sitting for long periods of time can make either condition worse. Bending or twisting can aggravate a bulging or herniated disk.

While it’s always helpful to pay close attention to your symptoms, imaging is usually necessary. MRI is a valuable tool to get a good look at bulging or herniated disks. I would also keep a pain diary to make a note of what your pain triggers are and where the pain occurs. Make a note also of what relieves the pain (if anything).

All of these things can be helpful with assisting your doctor in making a proper diagnosis. Only until you get the correct diagnosis can you take steps to begin treatment and possibly achieve some lasting relief.

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

Can Opioids Be Safely Used with Cannabis?

By Pat Anson, PNN Editor

Many doctors who prescribe opioids to pain patients tell them not to mix opioids with cannabis – fearing a combination of the two could raise the risk of addiction and overdose. Some doctors will stop prescribing opioids to patients or even discharge them if cannabis is detected in their drug tests.

But a new animal study suggests that cannabidiol (CBD) and tetrahydrocannabinol (THC) – the active ingredients in marijuana – may actually be safe to use with opioids and could be an effective way to lower opioid doses while still providing pain relief. 

“There is intense interest in using medical marijuana in patients with chronic pain because compounds in marijuana like CBD and THC may produce pain relief themselves or enhance the pain-relieving effects of opioids,” said Lawrence Carey, PhD, a postdoctoral fellow at the University of Texas Health Science Center, San Antonio. “This means people could potentially use lower doses of opioids and still get relief from pain. Taking less pain medication could also lead to a lowered risk of addiction or physical dependence to opioids.”

Carey and his colleagues tested their theory by giving rhesus monkeys dependent on opioids various doses of CBD and THC, either alone or together. The monkeys were then given opportunities to press levers that either gave them a food reward or an injection of fentanyl, a potent synthetic opioid.

Their findings, presented this week at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics, showed that CBD and THC did not increase or decrease the number of times the primates selected fentanyl over food. This suggests that cannabis does not enhance the rewarding effects of opioids or raise the risk of addiction, at least for rhesus monkeys.

“Giving the animals the opportunity to choose between a drug injection and a food reward helped us to somewhat replicate choices a human drug user may face, such as whether to spend money on drugs or food,” Carey said in a press release. “Having the option of responding for food is also useful for studying drugs like THC that produce sedative effects. It helps demonstrate the animal is reallocating behavior from drug to food choice instead of simply shutting down response for a drug due to sedation.”

Carey says more studies on humans are needed to determine whether THC and CBD are safe to use with opioids, and if they work well together.

A 2020 study of patients prescribed opioids for chronic low back pain found that half were able to stop using opioids after starting cannabis therapy, but it took an average of six years to do so. About 15% reduced their use of opioids and the remainder either kept taking the same amount or increased their opioid use.

Carey is now conducting animal studies to assess whether CBD and THC can decrease symptoms of opioid withdrawal. 

“A big reason why people continue to take opioids after they become addicted is the appearance of withdrawal symptoms,” said Carey. “We are using what we learned from this study to determine whether these doses — which didn’t alter choice for food or drug rewards — may help relieve opioid withdrawal or decrease relapse and drug seeking behavior following periods of abstinence.”  

Low Fat Vegan Diet Reduces Rheumatoid Arthritis Pain

By Pat Anson, PNN Editor

A small new study found that a low-fat vegan diet can help improve joint pain in patients with rheumatoid arthritis – the latest research to show that healthier diets can significantly reduce pain levels. Study participants also lost weight and lowered their cholesterol levels by eliminating their consumption of animal fats and inflammatory foods.

Rheumatoid arthritis (RA) is a progressive and incurable disease in which the body’s immune system attacks joint tissues, causing pain, inflammation and bone erosion.

“A plant-based diet could be the prescription to alleviate joint pain for millions of people suffering from rheumatoid arthritis,” says lead author Neal Barnard, MD, president of the Committee for Responsible Medicine. “And all of the side effects, including weight loss and lower cholesterol, are only beneficial.”

Thirty-two people diagnosed with RA from the Washington DC area completed the study after being assigned to one of two groups for 16 weeks.

The first group followed a vegan diet for four weeks, eliminating their consumption of meat, dairy products and eggs. During weeks 5 through 7, the diet was further restricted to eliminate gluten-containing grains, as well as potatoes, chocolate, nuts, citrus, onions, tomatoes, bananas, apples and coffee.

Vegan foods that participants were encouraged to eat included rice, oats, quinoa, broccoli, kale, collards, Brussels sprouts, squash,  carrots, apricots, blueberries, plums, lentils and beans. There were no restrictions on calories or how often they ate.

After week 7, the excluded foods were reintroduced, one at a time, every 2 days. Any food that was associated with pain or other symptoms upon reintroduction was eliminated

The second group followed an unrestricted diet but were asked to take a daily placebo capsule.  After 16 weeks, the groups switched diets.

The study findings, published in the American Journal of Lifestyle Medicine, showed a significant reduction in pain and inflammation during the vegan stage of the study. Participants lost an average of two points in their Disease Activity Score-28 (DAS28), which measures swollen joints, joint tenderness and C-reactive protein levels – a marker for inflammation. DAS28 levels typically increase with rheumatoid arthritis severity.

The average number of swollen joints decreased from 7.0 to 3.3 in the vegan phase, while increasing slightly for participants in the placebo phase.

In addition to reductions in pain and swelling, participants lost an average of 14 pounds on the vegan diet, compared with a gain of about 2 pounds on the placebo diet. There were also greater reductions in total, LDL, and HDL cholesterol during the vegan phase.

Notably, although participants were asked not to alter or reduce their use of medication during the study, several of them did so – in most cases because they felt less need for them.

“In conclusion, the current study suggests that a low-fat vegan diet eliminating specific foods, without fasting and without caloric restriction, may improve joint pain. Additional studies are needed in which the diagnosis is confirmed by independent observers and medications remain stable in a larger sample,” said Barnard.

Many previous studies have shown an association between healthy diets and lower pain levels. Gluten-free diets have been shown to improve symptoms of fibromyalgia and neuropathy, while Mediterranean diets rich in anti-inflammatory foods lower the risk developing chronic pain. And diets that include lots of fatty fish and less processed food reduce the frequency and severity of migraines.

One of the strictest diets of all – a very low energy diet (VLED) that limits people to just 800 calories a day – was recently found to significantly reduce fibromyalgia pain after just three weeks.

Long Covid Research Could Lead to New Treatments for Chronic Pain

By Pat Anson, PNN Editor

About a third of people infected with Covid-19 develop long-term symptoms, such as headaches, persistent muscle pain, joint pain, stomach pain, chest pain and respiratory discomfort. Three years into the pandemic, scientists are finally beginning to understand what causes long covid and how to possibly treat it.

In studies on hamsters infected with Covid-19, researchers at the Icahn School of Medicine found that the virus left behind a gene expression signature in the animals’ dorsal root ganglia – a cluster of nerves in the spinal cord that transmit pain signals from the body to the brain. The signature matched gene expression patterns seen in other forms of chronic pain.

“A significant number of people suffering from long COVID experience sensory abnormalities, including various forms of pain,” said Randal (Alex) Serafini, an MD/PhD candidate. “We used RNA sequencing to get a snapshot of the biochemical changes SARS-CoV-2 triggers in a pain-transmitting structure called dorsal root ganglia.”

Serafini presented his findings at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics in Philadelphia. 

The symptoms experienced by hamsters infected with Covid-19 closely mirrored those of people. Researchers say the hamsters showed a slight hypersensitivity to touch early after the infection, which became more severe over time.

They performed similar experiments with the Influenza A virus to determine if other RNA viruses promote a similar response. Influenza A caused an early hypersensitivity that was more severe, but began to fade after a few days. Four weeks after recovering from the flu, the hamsters had no signs of long-term hypersensitivity.

In contrast, hamsters infected with SARS-CoV-2-showed more hypersensitivity, reflecting symptoms of chronic pain. The pain sensitivity remained even after the hamsters recovered from the initial Covid-19 infection. Further research found that SARS-CoV-2 downregulates the activity of several previously identified pain regulators and a protein called interleukin enhancer binding factor 3 (ILF3) — a potent cancer regulator.

Based on these findings, the researchers hypothesized that mimicking the acute effects of ILF3 could serve as a new pain treatment strategy. To test this theory, they gave laboratory mice suffering from inflammation a clinically tested anti-cancer drug that inhibits ILF3 activity. The drug was very effective at treating their pain.

“Our findings could potentially lead to new therapies for patients suffering from acute and long COVID, as well as other pain conditions,” said Serafini. “We think therapeutic candidates derived from our gene expression data, such as ILF3 inhibitors, could potentially target pain mechanisms that are specific to COVID patients, both acutely and chronically.

“Interestingly, we saw a few cancer-associated proteins come up as predicted pain targets, which is exciting because many drugs have already been developed to act against some of these proteins and have been clinically tested. If we can repurpose these drugs, it could drastically cut down therapeutic development timeline.”

Serafini and his colleagues are now working to identify other compounds that could be repurposed to treat pain, while also keeping an eye out for new compounds that might inhibit ILF3 activity.

“Our study also shows that SARS-CoV-2 causes long-term effects on the body in drastically new ways, further underscoring why people should try to avoid being infected,” he said.

Another study has suggested that long covid appears to be the result of an overactive immune system. Australian researchers identified biomarkers of a sustained inflammatory response in the blood samples of long covid patients – suggesting their immune systems were activated by the virus, but then failed to turn off.

Other studies have found similarities between long covid and autoimmune conditions such as lupus and myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS).  

In addition to widespread body pain, long covid symptoms include fatigue, cognitive impairment and difficulty sleeping.    

Tiny Experimental Implant Could Treat Neuropathic Pain

By Pat Anson, PNN Editor

A tiny wireless implant that stimulates peripheral nerves from within blood vessels shows potential as a treatment for neuropathic pain, according to a proof-of-concept study by a team of Texas researchers published in the journal Nature Biomedical Engineering.

The implants have only been tested in laboratory animals, but researchers say they could replace larger and more invasive devices currently used to treat Parkinson’s disease, epilepsy, chronic pain, hearing loss and paralysis.

The MagnetoElectric Bio ImplanT -- ME-BIT for short -- is slightly larger than a grain of rice. It’s designed to be placed in a blood vessel near the nerve targeted for stimulation. The implant requires no surgery or batteries, and draws its power and programming from an electromagnetic transmitter worn outside the body.

“Because the devices are so small, we can use blood vessels as a highway system to reach targets that are difficult to get to with traditional surgery,” said lead author Jacob Robinson, PhD, Associate Professor of Electrical and Computer Engineering at Rice University.

RICE UNIVERSITY

“We’re delivering them using the same catheters you would use for an endovascular procedure, but we would leave the device outside the vessel and place a guidewire into the bloodstream as the stimulating electrode, which could be held in place with a stent.”

The ability to power the implant remotely eliminates the need for electrical leads through the skin and other tissues. Leads used for devices like pacemakers can cause inflammation and sometimes need to be replaced. Battery-powered implants may also require additional surgery to replace the batteries.

Researchers say ME-BIT’s wearable charger could even be misaligned by several inches and still provide sufficient power and programming to the implant, without irritating surrounding tissues.

“We’re getting more and more data showing that neuromodulation, or technology that acts directly upon nerves, is effective for a huge range of disorders – depression, migraine, Parkinson’s disease, epilepsy, dementia, etc. – but there’s a barrier to using these techniques because of the risks associated with doing surgery to implant the device, such as the risk of infection,” said co-author Sunil Sheth, MD, Associate Professor of Neurology and director of the Vascular Neurology Program for McGovern Medical School at UTHealth Houston.

“If you can lower that bar and dramatically reduce those risks by using a wireless, endovascular method, there are a lot of people who could benefit from neuromodulation.”

Electrical stimulation can reduce pain when doctors target the spinal cord and dorsal root ganglia (DRG), a bundle of nerves that carry sensory information to the spinal cord. But existing DRG stimulators require invasive surgery to implant a battery pack and pulse generator.

By using blood vessels, researchers say they can place the ME-BIT implant strategically in a minimally invasive way and have more predictable outcomes.

“One of the nice things is that all the nerves in our bodies require oxygen and nutrients, so that means there’s a blood vessel within a few hundred microns of all the nerves,” Robinson explained. “With a combination of imaging and anatomy, we can be pretty confident about where we place the electrodes.

In a previous study, Robinson and his colleagues demonstrated the viability of the implants by placing them beneath the skin of laboratory rodents that were fully awake and free to roam about their enclosures. The rodents preferred to be in parts of the enclosures where a magnetic field activated the implant, which provided a small voltage to the reward center of their brains.

Researchers need to conduct more animal studies and eventually human trials before seeking FDA approval for the implants.

“We’re doing some longer-term studies to ensure this approach is safe and that the device can stay in the body for a long time without causing problems,” said Sheth, who estimates the process will take a few years.

9.6 Million Counterfeit Pills Made with Fentanyl Seized in 2021

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

Opioid Sales Per Capita (2019)

SOURCE: THE LANCET

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

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

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

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

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

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

Therapy Dogs Reduce Pain in ER Patients

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

Medical Cannabis Is Losing Credibility

By Roger Chriss, PNN Columnist

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

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

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

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

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

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

Recent reviews of past studies are similarly disappointing.

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

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

Lack of Efficacy

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

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

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

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

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

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

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

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

New CBD Drug Developed for Postoperative Pain

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

Better Pain Treatment Needed for People with Severe Mental Illness

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

Chronic Pain Worsened for Many During Pandemic

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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