New Non-Opioid Analgesic Works Better Than Vicodin

By Crystal Lindell

An experimental non-opioid pain medication appears to outperform a low dose of Vicodin for patients who just had tummy-tuck surgery.

Latigo Biotherapeutics recently published results from its Phase 2 clinical trial in The New England Journal of Medicine, looking at the effectiveness of their new analgesic, which goes by the name LTG-001.

Like other new non-opioid analgesics, LTG-001 works differently than opioids because it blocks pain signals in the body’s peripheral nervous system before they reach the brain. Opioids act on nerve receptors in the brain, where they can slow down breathing and have a “euphoric” effect at high doses.    

In the clinical trial, 343 patients with moderate-to-severe post-operative pain after abdominoplasty surgery were randomly assigned to four groups. One group received low-dose LTG-001; another took high-dose LTG-001; a third took tablets of 5 mg hydrocodone and 325 mg acetaminophen (Vicodin); and the fourth group received a placebo. 

The LTG-001 doses were given orally every 12 hours, while the Vicodin tablets were taken every six hours, for a daily dose of 20 MMEs (morphine milligram equivalents). Patients also had the option to request oxycodone if their pain was getting too severe.  

When researchers asked patients about their pain levels, they found that the high-dose LTG-001 had a 50% greater analgesic effect than Vicodin. “Meaningful pain relief” was also achieved faster with high-dose LTG-001 than with Vicodin (52 minutes vs. 83 minutes).

But many in the high dose LTG-001 group were not able to stay “opioid free.” In a press release, Latigo highlighted the fact that over half (52%) of the patients taking LTG-001 didn’t need the oxycodone “rescue” medication.

Another way to look at that statistic is that the other 48% of patients did not have pain that was well controlled and wound up using opioids anyway. On average, patients in the high dose LTG-001 group still needed 11 MME of oxycodone for pain relief.

Despite the lackluster results, company officials said the clinical trial was “an important milestone for Latigo.”

“The publication of these findings adds to the growing scientific understanding of non-opioid approaches to pain management and comes at a time when there is broad recognition of the need for additional treatment options in the context of the ongoing opioid crisis,” Neil Singla, MD, Chief Medical Officer of Latigo, said in a statement.

Based on discussions with the FDA, Latigo believes the study may serve as one of the well-controlled trials needed to demonstrate the efficacy of LTG-001 to support its approval as a treatment of moderate to severe acute pain, including postoperative pain. 

The company’s next step is to initiate a placebo-controlled Phase 3 trial in participants undergoing bunionectomy and an open-label Phase 3 safety trial. Latigo is also investigating LTG-001 as a pain reliever after wisdom tooth removal.

Last year the FDA approved a similar non-opioid analgesic, Journavx. Although it is only approved for moderate to severe acute pain, it didn’t take long for Jourvanx  to be used off label for chronic pain.  A recent analysis of prescription data found that Jourvanx is prescribed about 33% of the time for chronic pain. In fact, it’s prescribed more often for chronic pain than opioids are.  

New Pain Reliever Combines Tylenol and Naproxen

By Crystal Lindell

Pain sufferers will soon be able to buy a new over-the-counter medication that combines acetaminophen with naproxen. 

That’s thanks to the FDA approving new “Tylenol with Naproxen.” A two-tablet dose contains 650 mg of acetaminophen and 220 mg of naproxen sodium. Many consumers know acetaminophen as the brand name Tylenol, while naproxen is known by the brand name Aleve. 

The non-prescription pain reliever is approved for minor aches and pains such as headaches, backaches, sore muscles, toothaches, menstrual cramps, and arthritis pain in adults and children 12 years and older. 

The new tablets start working within about 30 minutes because of the acetaminophen, while the non-steroidal anti-inflammatory drug (NSAID) naproxen provides 12 hours of extended pain relief.

Acetaminophen is believed to work more quickly to reduce pain signals, while naproxen provides longer-lasting relief by targeting pain caused by inflammation.

The FDA granted Kenvue, which makes the Tylenol brand, a three-year period of exclusivity for this new OTC formulation. That means there will be no generic alternative available in that time.

In a press release, Kenvue cited a recent company survey showing that 75% of pain sufferers report dissatisfaction with their current options.

“Persistent pain often leaves people trapped in a cycle of trial and error, navigating between choosing short-term relief or more complex treatment options,” said Rajesh Mishra, MD, Chief Medical Officer of Kenvue. “Tylenol with Naproxen simplifies that choice, offering fast onset, 12-hour duration, and the safety profile of two well-established non-opioid ingredients in one fixed-dose.”

The company said its research showed that Tylenol with Naproxen demonstrated superior pain relief versus using either medication alone. It didn’t provide a price or date for when the tablets will be available, only that they are “coming soon to major U.S. retailers nationwide.”

Company Touts ‘Opioid-Free’ Label

The press release touts the fact that the medication is "opioid-free" multiple times and claims "up to 1 in 4 patients prescribed opioids are at risk of addiction."

"Tylenol with Naproxen addresses this gap by combining two well-established non-opioid pain relievers into a single, clinically proven OTC therapeutic solution that requires no prescription and carries no opioid risk," the company said.

Most studies show the risk of opioid addiction is very low. Neither Kenvue or the FDA shared any research on whether the new medication was comparable to pain relief from opioids.

And just because there is no opioid-related risk, that doesn't mean there is zero risk. The FDA warned consumers not to use Tylenol with Naproxen with other drugs containing acetaminophen, as doing so may cause liver damage.

And, as with all NSAID-containing products, the labeling includes warnings for stomach bleeding and for increased risk of heart attack, heart failure, and stroke — risks that are higher when NSAIDs are used more than directed or for longer than directed.

While this is the first OTC combination of Tylenol with Naproxen, it is not the first time acetaminophen has been combined with an NSAID in an OTC medication. In 2020, the FDA approved the first over-the-counter pain reliever that combines acetaminophen with ibuprofen, Advil Dual Action.

Hydrocodone Is Better Than Oxycodone for Post-Operative Pain

By Pat Anson

When it comes to treating post-operative pain, hydrocodone works better than oxycodone in relieving pain and does it with smaller doses, according to a new study that compared the effectiveness of the two opioids.

A team of researchers evaluated health data for 663 patients who had elective joint arthroplasty on their hips or knees, a major surgical procedure where a damaged or arthritic joint is removed and replaced with an artificial one. About a third of the patients took oxycodone for post-operative pain, while the rest received hydrocodone. 

Nearly 1.25 million joint arthroplasty procedures are performed annually in the US, and many patients experience significant pain during recovery. Oxycodone is generally considered more potent than hydrocodone, and is typically prescribed more often for post-operative pain.

The study findings, published in JAMA Network Open, show that patients on hydrocodone had slightly lower pain scores 10 days after surgery than those who took oxycodone. 

They also needed significantly less morphine milligram equivalents (MMEs) over the course of their post-op recovery (93.2 MME for hydrocodone vs 134.8 MME for oxycodone).  

“We observed that patients prescribed hydrocodone had lower composite pain scores over the 10-day postoperative period, and their total opioid consumption (in MME) was significantly lower, compared with patients prescribed oxycodone. Therefore, we rejected our initial hypothesis that oxycodone provides better pain control than hydrocodone,” wrote lead author Julie Johnson, PharmD, Director of the Clinical and Translational Science Institute at The Ohio State University. 

It’s important to note that all of the participants in this study had the CYP2D6 gene, which makes them normal metabolizers (NMs) of opioids. Had they had a variation of the gene, oxycodone may have performed better, according to researchers. About 10% to 15% of individuals have those variants.

“Our findings have practical implications for postoperative pain management, especially in the context of personalized medicine and opioid-sparing strategies. For patients who are CYP2D6 NMs, a multimodal approach with hydrocodone appears to be a safe and effective option for managing acute post–total joint arthroplasty pain, achieving pain relief that was comparable to or better than oxycodone, with a lower MME,” Johnson wrote.

The hydrocodone and oxycodone formulations used in the study contained acetaminophen. Both groups also utilized other pain relievers, such as NSAIDs, nerve blocks and tramadol during their recovery. There were no significant differences in mobility, anxiety, and depression between the hydrocodone and oxycodone groups.

Non-Opioid Journavx Is Being Prescribed Off Label for Chronic Pain

By Crystal Lindell 

Here’s some news that many pain patients could have predicted: A non-opioid medication recently approved for acute, short-term pain is already being prescribed off-label for chronic pain. In fact, it’s prescribed more often for chronic pain than opioids!

Suzetrigine, which goes by the brand name Journavx, was approved by the Food and Drug Administration in January 2025. Unlike opioids, Journavx blocks pain signals in the peripheral nervous system, not in the brain, so it doesn’t have the same “liking” effects of opioids, which can lead to dependence or addiction.

Developed by Vertex Pharmaceuticals, Journavx was the first new medication for acute pain in over two decades, and is primarily intended for post-operative pain or emergency trauma care. 

But 15 months later, new data published in Epic Research shows that Journavx is often being prescribed for chronic, long-term pain instead.

The researchers studied health records for more than 3.6 million U.S. adults who received a new prescription for either Journavx or an opioid between February 2025 and April 2026.

They found that chronic pain accounted for 33% of the Journavx prescriptions. By comparison, opioids were prescribed just 6.7% of the time for chronic pain.

Opioid prescribing was concentrated in patients who had surgery (48.8%) or acute pain (19.8%), which together accounted for over two-thirds of the opioid prescriptions.

Only 10.2% of the Journavx prescriptions were for surgery and 31.8% were for acute pain.

"Suzetrigine adoption has been concentrated in specialties that manage chronic and surgical pain longitudinally rather than in the acute-care settings where opioids are most commonly initiated," the study found.

The Epic researchers found that patients prescribed Journavx were often older and more likely to be female than patients prescribed opioids. Specifically, 43% of Journavx patients were 65 or older, compared with 31.4% of opioid recipients. 

Off-label prescribing of a medication is perfectly legal and, in some cases, appropriate. But drugs are rarely put through clinical trials for those off-label purposes.

Results from clinical trials suggest that Journavx is a mild pain reliever, at best, for acute or chronic pain.

In Phase 3 clinical studies of acute pain after minimally invasive surgeries, Journavx was no more effective than a low-dose combination of hydrocodone and acetaminophen, more commonly known as Vicodin.

In a Phase 2 study, Journavx was essentially no better than a placebo in relieving chronic back and hip pain caused by lumbosacral radiculopathy.

Journavx is priced by Vertex Pharmaceuticals at a wholesale cost of $15.50 for a 50mg pill. When taken twice a day for acute pain, that works out to $420 for a one-week supply. By comparison, a supply of 100 Vicodin tablets costs about $142.

Journavx is currently only available in an oral formulation, which severely limits its use for post-surgical pain, where injectable or intravenous analgesics are often preferred. 

Short-Term Opioid Prescribing Should Be Tailored to Patient Needs

By Crystal Lindell

A new study has found something that every pain patient already knows: Opioid prescriptions “should be tailored to address individual patients’ needs.”

The research findings, which were published in JAMA, looked at how well opioids worked for 1,708 patients with short-term acute pain from a wide variety of conditions; from dental procedures and knee replacements to low back pain and cesarean sections.

The findings debunk common myths that many patients quickly become dependent on opioids and are unable to regulate their opioid use.

Overall, most of the patients used opioids for only a short amount of time – about 7 days –  and at low doses (10 MME). Only 10% of patients used opioids for 90 days or more, which is generally considered the threshold for acute pain becoming chronic.  

Overall, opioids were effective at relieving pain, with patients reporting a 55% reduction in pain on average. The median time to pain resolution was 20 days, although patients with low back pain or recovering from surgery took longer than that.

Most patients continued to use non-opioid pain relievers such as acetaminophen or ibuprofen, and also used ice or heat as part of a “multimodal treatment” approach.

About two-thirds of patients had leftover opioids. Interestingly, they were often patients with the longest-lasting pain conditions, which suggests they chose “not to continue using the opioids they had available” even when their pain persisted.   

Current guidelines from the CDC and FDA for acute pain recommend opioids only for severe pain or when non-opioid pain medications are ineffective.

Given the wide variety in outcomes and patient preferences, researchers say their findings demonstrate that guidelines for short-term opioids should be tailored to each patient. Most patients in the study were pretty good about moderating their opioid use. 

“Patients generally reported taking opioids on their worst pain days, in small amounts, for short periods, and in combination with other pharmacologic and nonpharmacologic treatments, with many patients limiting their opioid use to less than the amount prescribed by their clinician,” wrote lead author Molly Moore Jeffery, PhD, of the Mayo Clinic.  

“The findings suggest current guidelines for multimodal treatment and short-duration opioid prescriptions, if needed, will serve many patients but not all and that treatment should be tailored to address individual patients’ needs.” 

A recent study found that opioids are effective for many acute pain conditions and come with little risk. In a review of 59 clinical studies, researchers at the University of Sydney found that opioids were effective for “the vast majority of acute pain conditions,” with no significant risk of serious adverse events.

More Non-Opioid Drugs Recommended for ER Pain Relief

By Pat Anson

Would you take an anti-depressant for back pain? 

An anti-psychotic medication for headache?

What about an anti-anxiety drug for stomach pain? 

Those are some of the non-opioid alternatives being recommended for pain relief in emergency rooms, as the healthcare industry continues to move away from using opioids.

The latest example is a study by researchers at University of California, San Francisco (UCSF), who recommend over a dozen non-opioid medications for five acute pain conditions commonly treated in emergency departments: back pain, abdominal pain, chest pain, fracture pain and headache. 

The findings are published in the Western Journal of Emergency Medicine.  

Researchers initially screened 246 clinical studies to prepare their non-opioid list, but narrowed it down to 23 of the most promising studies. First author Akash Shanmugam, a UCSF medical student, told The Guardian that the goal was to “create a very targeted list for specific pain conditions” to be utilized by ER physicians.

Many of the drugs that made the list, such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are already widely used for acute pain. But some of the selections are puzzling, as they are psychotropic drugs not typically used to treat pain and are not fast-acting.

For example, the anti-psychotic drug haloperidol is recommended for both headaches and abdominal pain. Haloperidol is usually prescribed for schizophrenia or acute agitation, and is sometimes used off-label for conditions like psychosis and Tourette's syndrome.

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is typically used to treat depression and anxiety, but UCSF researchers think it could be used for back pain.

Other oddities that made the non-opioid list are ketamine for chest pain, abdominal pain and headache; benzodiazepines for abdominal pain; and the anti-nausea drug metoclopramide for headaches. 

Gabapentin would have made the list of non-opioid alternatives, but researchers decided the evidence was too weak to support its use for the five conditions they evaluated.  

“Our findings hold significant implications for pain management approaches in the ED and public health efforts aiming to address the opioid epidemic. By providing alternatives to opioid prescriptions, this review supports efforts to reduce opioid overexposure in the ED while helping to manage patient pain,” researchers said.

“Encouraging the use of these alternatives aligns with broader initiatives aimed at optimizing pain management practices, improving patient outcomes, and contributing to the overall mitigation of the ED’s contribution to the opioid crisis.” 

‘Made Me Feel Worse’

But are the drugs effective for pain? Posters on Reddit are skeptical that antidepressants and anti-psychotics would be helpful.

“This is ironic because codeine does a better job of making my brain quiet than any antidepressant I've tried so far,” said one poster. “I've never developed an addiction to codeine and it's also never induced suicidal thoughts, unlike a couple of the antidepressants I've tried. It also didn't make me so physically sick that I almost went to hospital, unlike the SNRI I stopped taking.”

“Tried tons of antidepressants for pain and depression, nothing worked in fact many made me suicidal. And then had tramadol prescribed for my back pain, low dose but my depression also improved a huge amount,” wrote another.

“These types of medications have made me feel worse than anything else I’ve ever taken. If I had to choose between pain and feeling like that again, I would choose the pain. But maybe that’s what they’re after since doctors don’t like prescribing pain medicine anyway,” said another Reddit poster.

“That's just ridiculous. Antidepressants and antipsychotics are not going to do anything at all to relieve pain,” said another. “The war on drugs has gone too far.”

But researchers say there’s frequently an overlap between physical and emotional pain that justifies the use of psychotropic drugs.

“Chronic pain is often linked to things like poor sleep, depression, anxiety, fatigue,” co-author Kathy LeSaint, MD, Associate Professor of Emergency Medicine at UCSF, told The Guardian. “In chronic pain conditions, the nervous system can become highly sensitive, and it’s thought that antidepressants and antipsychotics can maybe reduce this heightened sensitivity in the brain.”

Although the risk of addiction and overdose are often cited as reasons to avoid using opioids, that risk is often exaggerated. A 2024 study found that the risk of long-term opioid use after being treated with intravenous opioids in the ER is quite low – less than two-tenths of one percent (0.19%).

That mirrors the findings of a 2017 Mayo Clinic study, which found that the risk of long-term opioid use is only 1.1% for ER patients — less than it is for patients treated in other medical settings.

Nevertheless, some pharmaceutical companies are betting that non-opioids are the future of pain relief. Eli Lilly today announced the purchase of 4E Therapeutics, a biotechnology company that’s developing MNK inhibitors, which interfere with pain signals by blocking enzymes in the peripheral nervous system. 4E is the second non-opioid drug developer to be acquired by Lilly in a little over a year.

A Fentanyl Vaccine Is a Horrible Idea

By Crystal Lindell

A few years ago, I saved a loved one’s life when he was overdosing on fentanyl.

His lips and fingertips were blue when I found him, and as I administered NARCAN (naloxone), all I could think at that moment was that if he was dead, I never got the chance to say good-bye.

It was one of the most traumatizing experiences of my life, and I’m forever grateful that my efforts to save him were successful.

Even with that experience, I’m here to tell you that a fentanyl vaccine is an absolutely horrible idea. And I pray that nobody I love ever takes it – even the man who’s life I saved.

This week, JAMA published an article about the current status of the fentanyl vaccine, which is in development.

In the article, Associate Managing Editor Kate Schweitzer interviews Collin Gage, a cofounder and chief executive officer of ARMR Sciences, which has begun early-phase human trials of a fentanyl vaccine in the Netherlands.

Schweitzer seems to think such a vaccine would be a net positive for the world.

"If proven safe and effective, it could become the first proactive pharmaceutical approach designed to prevent fentanyl overdose and, potentially, treat addiction," she writes.

However, as both a chronic pain sufferer and someone whose loved one struggled with fentanyl addiction, I’m here to tell you that this entire research project should be ended right now.  

First and foremost, my biggest concern is that such a vaccine would be pushed onto people who do not want or need it, including pain patients.

I can already see doctors having a policy where they won’t prescribe opioids unless the patient agrees to receive the fentanyl vaccine. They’ll claim the policy is meant to protect patients, when in reality, it would only cause them more harm.

The article even points out what those harms could look like. Schweitzer quotes Kathryn Frietze, PhD, associate professor of molecular genetics and microbiology at the University of New Mexico, who is one of many researchers working to develop vaccines against drugs of abuse.

Doctors, according to Frietze, have expressed concern about how a vaccine could complicate medical care, given that prescription fentanyl is a widely used medication for acute pain control and anesthesia.

“Can they increase the fentanyl dose medically if needed, or is it going to completely eliminate fentanyl as an option?” Fritze asked. 

Read that again. Do we really want to eliminate fentanyl as an option for pain control and anesthesia? This is a medication used in hospitals, usually on patients in severe trauma or undergoing surgery.

Do we really want a vaccine to make fentanyl ineffective for them? 

Do we really want a vaccine that requires more fentanyl to be administered?

In practice, either scenario could be disastrous, especially in an emergency situation where an unconscious patient would be unable to explain to doctors that they had the fentanyl vaccine.

The thing about fentanyl is that you have no idea that you might need it someday. We don’t usually know when we’ll need anesthesia or acute pain control.

That is particularly relevant in this situation, because the article quotes multiple experts who seem excited about pushing a fentanyl vaccine onto high-risk groups, such as college students and young adults, who are experimenting with drugs. They may not be aware that the counterfeit pill they bought or got from a friend has a lethal dose of fentanyl. 

“Overdose from fentanyl doesn’t just happen to people who are purposely taking fentanyl,” Frietze said. “People may be exposed without their knowledge.” 

So they want to go to college campuses and give students a vaccine against a very valid pain medication, when they have no idea if they will ever need it?

Schweitzer says a vaccine that specifically targets fentanyl could still allow for the use of other analgesics, such as morphine and propofol. 

As a pain patient, I’m skeptical about that. If a vaccine blocks the effects of one opioid, it may also dampen the effects of other ones.  

The other major issue with a potential fentanyl vaccine is a phrase coined by Richard Cowan in 1986: “The Iron Law of Prohibition.” That essentially means that when law enforcement targets a specific drug, the potency of other prohibited substances increases.

Or, as Cowan said, "The harder the enforcement, the harder the drugs."

If you give everyone fentanyl vaccines, people will just find even stronger drugs to take. And those drugs will likely be more deadly. It’s no coincidence that illicit fentanyl arrived on the black market just as opioid pain medication became harder to get. 

As such, a fentanyl vaccine could result in more overdose deaths, not less, as people seek substitute drugs that bypass the vaccine.

Gage’s response to that possibility is to call the fentanyl vaccine “a platform technology—one that we plan to adapt."

In other words, they will just make new vaccines for new drugs. But in practice, how long would it take to actually develop new ones? And how long would it take to get them to drug users, who are often difficult for the medical community to reach?

Trust me when I tell you that drug users and their dealers will move exponentially faster than any research and development team ever could.

In practice, the reason street fentanyl is so deadly is because it’s unregulated. Users don’t know how much they are taking or what is mixed in with it – and those two things make it more likely that the drug will cause an overdose.

The solution then is to offer drug users a regulated supply, which is what methadone treatment is. In a perfect world, if they really wanted to help fentanyl users, these researchers would be working to make methadone treatment more accessible.

Instead, they’d rather make it so patients can’t use one of the most effective pain and anesthesia medications on the market, while pushing them onto harder or less effective drugs.

It’s a bad idea, and I hope these researchers see the error of their ways before it’s too late.

Tell Me Who the Real Criminals Are

By Cathy Kean 

Close your eyes. Go back to the worst pain you have ever known. A broken bone. A car wreck. Surgery. Childbirth without relief. Stay there for fifteen seconds. 

Feel the desperation. The begging. The need for it to stop.

Now imagine never leaving that place. You feel that pain every second. Every day. No break. Not in sleep. Not ever.

That is my life. Millions of us live here.

There is something that helps. Prescription opioids do not erase my pain, but they turn down the volume enough for me to be able to shower. To work. To keep my home. To hug my grand child without screaming inside.

Then they took them away. They said it was for my own good.

Before my chronic pain worsened after the release of the CDC opioid guideline, I worked as a real estate agent and special education advocate. 

Now I cannot walk. I have lost my job. My home of 32 years is in foreclosure. Friends stopped calling. I need help to use the bathroom. My independence is a corpse they are still kicking.

And the final cruelty? The people who did this lied to you.

CATHY KEAN

The Lies Behind the ‘Opioid Crisis’

You have been told prescription opioids are killing America. In 2021, the CDC reported a 1,040% increase in overdose deaths involving synthetic opioids from 2013 to 2019. They said those deaths were largely caused by illicitly manufactured fentanyl.

Here is what they didn’t tell you in that report: For many years, CDC misclassified most of those overdoses as prescription opioid deaths, and those deaths were used to help justify the agency’s 2016 opioid guideline, which led to wholesale restrictions on opioid prescribing. 

Not until 2018 was the error quietly acknowledged by four CDC researchers. And that tens of thousands of illicit fentanyl deaths were misclassified for years as prescription opioid deaths. 

The error was so serious that in 2016 alone, over 15,000 deaths caused by illicit fentanyl were mistakenly attributed to prescription opioids. Millions of Americans were misled by these and other errors that inflated the overdose numbers.

The White House told you prescription painkillers were the enemy. The media screamed it. Meanwhile, the real causes – illicit fentanyl, heroin and methadone – were hidden inside the CDC's overdose numbers.

The Death Toll They Won't Count

Because of the CDC guideline, thousands of chronic pain patients killed themselves. 

Not because they wanted to die, but because they could no longer get the prescription opioids that made life bearable. The pain became more than they could endure. And suicide offered a way out.

Others died slowly. From heart failure. Stroke. Organ collapse. The brutal physics of untreated pain grinding a body into dust.

No one in power keeps track of those deaths or says a word about them. No government agency. No major news outlet. No one with a microphone stands up and says, "We made a mistake. We are killing innocent people."

Instead, they push Suboxone and “alternative treatments.” For money. Not thy fellow man.

We have lost our First Amendment rights in the doctor's office. If you speak up about your pain, you are labeled a drug seeker and abandoned as a patient. I would rather die at home than face contempt again in the ER.

What I Want You to Do

Now imagine those 15 seconds of the worst pain you’ve ever felt. Really do them. Feel that pain.

Could you live like that? For one week? One year?

I am not asking for your pity. I am demanding your understanding. Your voice. Your outrage.

We are not criminals. We are not drug seekers. We are not addicts. We are not statistics on a CDC spreadsheet.

We are mothers and fathers. Veterans who served you. Construction workers who built your cities. Nurses who held your hand. Grandparents who babysat your children.

And we are dying. Some by suicide. And some by the slow, grinding destruction of our lives and bodies.

So here is what I need from you:

Do not look away. Say our names. Help us get our lives back.

Because if you could spend fifteen seconds in my body — really spent them — you would not need to be asked twice. You would be screaming with us.

Cathy Kean lives in California. She is a grandmother of 9 and mother of 4. Cathy lives with intractable pain from a botched surgery, along with fibromyalgia, arachnoiditis, stiff person syndrome, lupus, Parkinson's disease and insomnia. 

Cathy is the creator and administrator of the Facebook pages Chronic Illness Awareness and Advocacy Coalition and Pain is Pain. She writes to give a voice to the millions of chronic pain patients who have been silenced, stigmatized, and left to suffer—and to ensure her grandchildren never have to ask why Grandma couldn't be there. 

CBD Enhances Oxycodone’s Pain Relieving Effects

By Pat Anson

Some pain sufferers firmly believe that cannabis can help boost the pain relieving effects of prescription opioids. The evidence behind that belief is mostly anecdotal, but some new research lends some credence to it.

In studies on laboratory rats, researchers at the University of Florida and Texas A&M University College of Dentistry found that cannabidiol (CBD) appeared to enhance the pain-relieving effects of oxycodone without increasing the risk of addiction. 

CBD is one of the many cannabinoids found in cannabis. It does not have the same psychoactive effects of tetrahydrocannabinol (THC), but is believed to have some therapeutic benefits.

The rats were treated with CBD, oxycodone or a combination of the two daily for two weeks, while acute pain was induced in the laboratory.

The study findings, published in The Journal of Pain, found that CBD enhanced oxycodone’s antinociceptive effect, meaning it blocked pain signals from reaching sensory neurons in the brain. CBD also did not affect the “rearing behavior” or “place preference” of rats, activities that may have suggested they were becoming dependent or addicted to oxycodone.

“Together, these findings suggest that cannabidiol potentiates the analgesic effects of oxycodone without affecting its reward-related properties. These results support the potential of cannabidiol as an adjunctive, opioid-sparing agent in pain management,” researchers wrote.

A recent study of 21 people with knee osteoarthritis reached a very different conclusion, finding that a low-dose of opioids taken with a cannabis-based medicine did not relieve acute pain. 

That study, however, was deeply flawed. The cannabis-based medicine was dronabinol (Marinol), a synthetic version of THC. Dronabil is FDA-approved to treat nausea and improve appetite, but is not intended to provide pain relief. The medication also has little in common with the various forms of cannabis (edibles, smoking, vaping) used in the real world.  

Granted, the use of dronabil and laboratory rats are major weaknesses in both studies, which highlights how cannabis research has long been stifled in the U.S. by marijuana’s status as an illegal Schedule I controlled substance.     

The DEA is now allowing more cannabis to be used for research purposes and recently reclassified medical marijuana as a Schedule III drug, which allows for medical uses. It could be years, however, before we see more high-quality studies about the risks and benefits of cannabis products.  

A Simple Chart Destroys a Myth About the Opioid Crisis

By Neen Monty

There’s a simple reason the narrative around the “opioid crisis” falls apart when you actually look at the overdose data.

Because the data doesn’t show what they claim it shows. 

And that false narrative has been retrofitted to cover the deception and lies wrought by bad actors in the U.S. healthcare system.

The chart below tracking overdose deaths by opioid type tells two stories:

1. Prescription opioid deaths rose, stabilized, and then fell.

2. Fentanyl arrived… and everything exploded.

Those are not the same curve. Those are not the same problem.

There are two epidemics. And one deliberately blurred narrative.

In the United States, prescription opioid deaths peaked around 2012, at about 5 deaths per 100,000 Americans. 

Meanwhile, fentanyl-related deaths – almost non-existent before 2012 – began rising exponentially as illicit fentanyl entered the black market.

In 2023, they peaked at 22.2 deaths per 100,000 people. By then, overdoses linked to prescription opioids had fallen to 3.8 deaths per 100,000.

That means there are almost 6 times the number of overdose deaths caused by illicit fentanyl than prescription opioids.

Yet prescription opioids remain the target.

That “opioid crisis” curve?

That’s illicit fentanyl. Not pain patients. Not prescription opioids. Not doctors treating disease.

The Uncomfortable Truth

When overdose deaths skyrocketed, prescription opioid deaths were already flattening out and falling. That should have changed the narrative right there.

But the narrative stayed the same.

The explosion in deaths aligns with one thing: iIlicit fentanyl and its analogues flooded the U.S. drug supply with counterfeit pills of unknown, often lethal, potency.

That is why deaths surged, not because someone with intractable rheumatoid arthritis got oxycodone prescribed for their pain.

The numbers don’t lie. If the opioid crisis were really about prescriptions, the lines on the chart would look very different.

So why didn’t the narrative charge?

Because blaming illicit fentanyl means:

• Confronting illicit drug supply chains

• Admitting policy failure

• Acknowledging complexity

Blaming prescriptions is easier. It creates easy villains to target:

• Doctors

• Patients

• Pain medication

And it opens the door to:

• Restrictions

• Guidelines

• “Education programs”

• Entire industries built on fear

Who paid the price?

Pain patients. People with cancer, autoimmune disease, neurological damage, and severe structural pathology.

People who were stable. Functioning. Living.

Until they were cut off.

This was never about prescriptions. The chart makes one thing brutally clear: The U.S. overdose crisis is a fentanyl crisis.

Everything else is a false narrative. A fairy story. One designed to vilify people who are already among the most vulnerable people in our communities – the ill, the disabled, people living with severe pain.

It’s important to note that by the time Physicians for Responsible Opioid Prescribing (PROP) was created in 2012, prescription opioid deaths had already stabilised and were falling.

PROP was instrumental in creating the CDC’s infamous 2016 opioid prescribing guidelines. But there was no need to restrict opioid prescribing. There was no need for forced tapers that lead to suicides and overdose deaths. There was no need for dose ceilings that meant people’s pain was no longer treated adequately.

There was also no need for the fabrication of “evidence” that does not stand up to even a little scrutiny. Just read the studies that the CDC guidelines are based on. They do not show what you have been told they show.

But no one actually reads the studies. No one examines the data. No one questions. Doctors just blindly follow the guidelines. It’s hard to blame them when they face prison time if they don’t.

It has been ten years since the forced tapers started in the U.S. Six years since Australia blindly copied this failed policy. No one in Australia bothered to read the research. Australia just copied the U.S. guideline and allowed politicians to decide who gets pain relief and who does not.

Australia could see the policy going horribly wrong in the U.S. Yet it implemented those same policies and tortured Australian chronic pain patients the same way. The same is true for Canada and the UK as well.

This should never have happened.

Patients on three continents have been abandoned, left to suffer in agony day after day. Given psychological therapies for physical disease and injury. And no one says a word. 

I have contacted many politicians, journalists, and senior public servants in Australia.  No one will take this on. No one will right this wrong.

And the media continues to push a false narrative about an opioid crisis that does not exist. But it gets clicks.

It may be futile, but my life and those of many others depend on access to safe and effective opioid therapy.

And so, I will continue to fight.

Neen Monty is a patient advocate in Australia who lives with rheumatoid arthritis and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a progressive neurological disease that attacks the nerves.

Neen is dedicated to challenging misinformation and promoting access to safe, effective pain relief. For more information on chronic pain, the science, the politics and the lived experience, go to Pain Patient Advocacy Australia. You can also subscribe to Neen’s free newsletter on Substack: “Arthritic Chick on Chronic Pain.”

CYP2D6: The Enzyme That Determines How Effective an Opioid Is

By Dipa Kamdar

For a medicine so commonly found in bathroom cabinets and high street pharmacies, codeine has a surprisingly complicated story. It sits at the intersection of pain relief, genetics, public health and regulation. 

As the UK and other countries continue to tighten rules around opioid use, codeine offers a useful case study in how a drug can be both helpful and potentially harmful, depending on who takes it and how it is used.

Codeine is an opioid used to treat mild to moderate pain. In some formulations, it is also used to suppress coughing. Over-the-counter products typically combine it with paracetamol, as in co-codamol, or ibuprofen, while stronger doses are available only on prescription.

Codeine itself is a weak opioid. Its analgesic effect is about one tenth that of morphine. Once swallowed, it is metabolised by enzymes in the liver, with some of it converted into morphine. That morphine then produces pain relief by acting on opioid receptors in the brain. 

For most people, the body makes enough morphine to ease symptoms. For others, the same dose can be ineffective or unexpectedly strong.

Fast vs Poor Metabolisers

One of the most striking features of codeine is how differently people process it. The enzyme mainly responsible for converting codeine into morphine, CYP2D6, varies significantly between people. Most metabolise codeine at an expected rate, but some carry genetic variants that alter the process.

A small proportion of the population are ultra-rapid metabolisers, thought to make up around 1% to 2% of people. They convert codeine into morphine much faster than average. 

This trait is more common among people of North African and Middle Eastern backgrounds, for whom even standard doses can produce unexpectedly high morphine levels, increasing the risk of severe drowsiness, breathing difficulties and other serious side effects.

Around 2% to 11% of people are intermediate metabolisers. Their CYP2D6 enzyme works more slowly or less effectively, so codeine may provide only limited benefit.

At the other end of the spectrum are poor metabolisers, estimated to make up 5% to 10% of the population. They convert very little codeine into morphine, so the drug may offer little or no pain relief. 

Poor metabolism is more common in people of white European descent. In these cases, it may make more sense to prescribe a different painkiller rather than rely on a drug the body cannot use efficiently. This wide variation makes codeine far less predictable than many people assume.

The Trouble With Codeine

That unpredictability matters because low-dose codeine does not always offer much in return. Research suggests that many over-the-counter codeine products provide little proven benefit for pain relief, particularly at doses below 10mg, while still carrying the risk of side effects. 

A review found that low-dose codeine combinations gave only modest relief for short-term pain, such as dental pain, episiotomy pain or pain after minor surgery, and many of the underlying trials were small.

By contrast, combinations such as ibuprofen 400mg with higher-dose codeine, between 25mg and 60mg, appear to provide more reliable relief. Even so, studies suggest that simple combinations such as paracetamol plus ibuprofen can match or outperform low-dose codeine products without the risks associated with opioids.

Common side effects include constipation, nausea, dizziness and drowsiness. At higher doses, codeine can slow breathing and impair coordination. It can also interact with other medicines that cause sedation, including some antiepileptic drugs. Certain antidepressants can block the enzyme that converts codeine into morphine, making it less effective.

Like other opioids, codeine can also become less effective with repeated use. This process, known as tolerance, happens when the brain’s opioid receptors adapt to the drug. People may then need higher doses to achieve the same effect. Even when taken as directed, tolerance can develop within days, and as doses rise, so does the risk of physical dependence.

Stopping suddenly after regular use can trigger withdrawal symptoms such as restlessness, sweating, anxiety and poor sleep. This is why health professionals advise using codeine for the shortest possible time and tapering the dose if it has been taken for longer periods.

Concerns about misuse, addiction and accidental harm have prompted tighter regulation in the UK. The Medicines and Healthcare products Regulatory Agency has introduced clearer warnings on packaging about addiction risk and limited over-the-counter pack sizes to a maximum of 32 tablets or capsules. Non-prescription codeine-containing products are now intended for use for no more than three days. Stronger codeine tablets, including 30mg formulations, have long been prescription-only.

Some products have faced even stricter controls. Codeine linctus, once widely used as a cough suppressant, was reclassified as prescription-only in 2023 because of growing concerns about misuse and diversion. 

It has been used in “purple drank”, a recreational mixture of codeine cough syrup with soft drinks and sometimes alcohol. Its opioid effects can lead to dependence, breathing difficulties and overdose, especially when combined with other sedatives.

Codeine remains a useful option for short-term pain when other medicines are unsuitable or insufficient. But its effectiveness, safety and potential for dependence vary far more than many people realise.

In a landscape where medicines are often judged by how familiar they feel, codeine is a reminder that common does not always mean simple. Used carefully, it can help. Used carelessly, it can cause problems that last long after the pain itself has passed.

Dipa Kamdar is a Senior Lecturer in Pharmacy Practice at Kingston University.

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

Many Rx Opioids – Not Just Suboxone – Raise Risk of Dental Disease

By Pat Anson

Suboxone isn’t the only opioid medication linked with dental decay and disease.

A large study led by VA Connecticut researchers found that patients on long-term opioid therapy with pain medications such as morphine and oxycodone have a significantly higher risk of infection-related dental disease.

The observational study included data from over 2 million U.S. veterans, 36% of whom were on long-term opioid therapy (LTOT). Those taking opioid pain medication for at least 90 days had a 24% higher chance of tooth decay, infections or tooth loss. 

Suboxone, which contains the partial opioid agonist buprenorphine, was excluded from the study, along with the opioid methadone. Both medications are used to treat opioid use disorder (OUD). 

The FDA warned in 2002 that buprenorphine tablets and film, when dissolved in the mouth, were linked to serious dental problems, including tooth decay, cavities, oral infections, and loss of teeth. Methadone has also been associated with dental problems because it induces dry mouth (xerostomia), which reduces saliva needed to wash away bacteria and plaque.  

The new study is believed to be the first linking dental disease to opioids taken long-term for pain relief.

“To our knowledge, this is the first study to demonstrate the association between LTOT exposure and dental disease. This finding is important in light of recent warnings of buprenorphine risks that may influence decision-making in the context of chronic pain and/or OUD,” researchers reported in the journal PLOS One.

In their analysis, VA researchers compared veterans who took 12 opioids (hydrocodone, oxycodone, morphine, fentanyl, hydromorphone, dihydrocodeine, meperidine, pentazocine, propoxyphene, levorphanol, tramadol, or tapentadol) to veterans who had no exposure to LTOT in the prior year.

Researchers think the higher rate of dental disease for those on LTOT stems from immune suppression and reduced saliva flow, which raises the risk of bacterial infections that lead to dental disease and cavities. 

The findings suggest that all patients on LTOT – whether for pain relief or OUD treatment – should be cautioned about the risks of dental problems.

“Concern over these risks may present a barrier to buprenorphine initiation in patients prescribed LTOT for whom such treatment is indicated. However, full opioid agonists themselves may pose oral health risks due to immunosuppression and well-documented effects on saliva flow causing xerostomia; both create opportunity for oral disease development,” researchers concluded.

Doctors who have patients on LTOT are advised to monitor their oral health and to have discussions with patients about dental risks before starting them on opioids.

There are simple steps patients on long-term opioids can take to reduce their risk of dental disease. Patients on buprenorphine or methadone are often advised to drink more water to combat dry mouth, and to brush and floss regularly to help prevent dental infections. 

The Fake Excuses Pharmacists Use to Avoid Filling Opioid Prescriptions

By Crystal Lindell

I still remember the first time a pharmacist lied to me about why they couldn’t fill my opioid prescription.

I went in to pick up my regularly scheduled morphine refill, and when I got to the counter, she told me that my insurance wouldn’t cover two prescription refills within the same calendar month. She claimed that the rule applied even if the refills were 30 days apart due to a month having 31 days. And, since the insurance wouldn’t cover it, they weren’t filling it.

At the time, it didn’t even occur to me that a pharmacist would blatantly lie to me about something like that. So I immediately walked away from the counter and pulled out my cell phone to call my insurance company.

I’m not going to lie, I had a whole rant ready to spew at them about this nonsensical rule.

As it turned out, my frustration was misplaced, because no such nonsensical rule existed. In fact, the representative told me no one from the pharmacy had attempted to even put the prescription through. If they had, the insurance company would have covered it.

When I went back to the pharmacy counter and relayed this information, the pharmacist shrugged and said it must have been a mistake. Then, she filled my prescription – which was indeed covered by insurance.  

It wouldn’t be the last time I would have to deal with a lying pharmacist.

Over the years I’ve realized that it’s common for pharmacists to throw up false hurdles when patients try to fill any type of controlled substance script. This includes opioids, but also stimulants like those prescribed for ADHD.

I’ve seen it happen many times to myself and loved ones. Their excuses seem to fall into three broad categories.

Claim #1: Insurance won’t cover the medication

This ties into my opening story here, but it’s also happened to me and my loved ones a number of other times.

For example, after my mom had a hip replacement surgery, the pharmacist tried to tell her that her insurance would only cover a specific number of pills, so they did not fill for the entire amount. My mom was too out of it to argue with them and just accepted the smaller amount – which is what the pharmacist was likely hoping would happen.

A related claim here is that the pharmacy can’t take cash payment for a controlled substance in cases where insurance is refusing to cover it. They never even offer the option in this circumstance, despite the fact that generic pain medications are relatively cheap, and many patients would be happy to pay cash if it meant getting their meds.

I can only speak to Illinois, but as someone who’s been living without health insurance since 2022, I can confirm that pharmacies here can definitely take cash for a controlled substance.

Claim #2: The pharmacy never received the prescription from your doctor

Just last week, one of my loved ones called his pharmacy when his pain medication was due to be refilled and the staff told him that they had not received the prescription. He asked them to check different computer files to see if they were missing it, because he was sure his doctor had sent it in.

The pharmacy staff insisted that they had not received it. It was a Saturday, so he was unable to get a hold of his doctor.

He called back on Sunday morning and they again claimed they had not received the prescription, but after he pushed them to look for it in different places they suddenly found it.

When he finally got the bottle, it said the prescription had been dated for that Saturday, meaning they had definitely lied about not receiving it the day before.  

Claim #3: The medication is completely out of stock

This is one that’s difficult to prove, but it happens so frequently that I have to assume that at least some of the time pharmacists are lying about being out of a medication. It’s an excuse they can give to avoid filling a prescription. 

Even if they aren’t lying about it, there’s nothing the patient can do to prove it. Opioids at many pharmacy chains are essentially being rationed due to opioid litigation settlements.

Beyond the direct lies, pharmacists use other tactics to make getting refills more uncomfortable and difficult. I assume that their hope is that it will deter patients from coming back.

For example, my current pharmacist will sometimes decide that he needs to discuss my opioid usage with me, and have a talk with me encouraging me to lower the dosage. It’s always an awkward and unwelcome conversation, and just the possibility of it happening makes me dread going in there every month.

My pharmacist has also tried to tell me that I needed a Narcan prescription to get another refill. The problem is I would have to pay cash for it, because I don’t currently have insurance. Thankfully, I convinced him that I already had Narcan at home – which was true. But I could see other patients giving up and leaving without their refill.  

The thought process among pharmacists seems to be that if they give pain patients enough hurdles to jump before they can get their opioid prescriptions, that some will just give up. That keeps more opioids out of patients’ hands.

I think pharmacists underestimate how much harm they cause when they straight up lie to patients. They see what they’re doing as protecting people from the supposed harms of opioids. But what they’re actually doing is eroding patient trust in them and medical professionals in general.

When pharmacists lie about being unable to fill prescriptions, it makes me wonder what else they are lying about. And it’s not a far leap to start questioning other medical information they provide.

I’m not sure what the solution is to all of this, other than to call out the behavior and to make more patients aware that it could be happening to them. People should know that they aren’t crazy, and that it’s okay to push back if you think the pharmacy is lying.

Maybe one day there will be more regulations in place to protect patients from being lied to by pharmacists. Or maybe pharmacists will be replaced by artificial intelligence programs – which may come with brand new problems that we haven’t even considered yet. 

Until then, my hope for you is that the next time you need to get a controlled substance prescription filled, the whole process goes so smoothly that it’s ready for pick up before you even get to the pharmacy.

Clinical Trials Were Used as Marketing Ploys for Gabapentin and Other Drugs

By Sukhun Kang

Some clinical trials aren’t designed to answer scientific questions. They’re designed to market drugs. 

In our recently published research, my team and I analyzed over 34,000 industry-funded trials and found that hundreds of studies across seven medical fields were likely designed to promote a drug to physicians rather than to generate scientific data. For some fields, nearly 1% of clinical trials were for marketing purposes.

Known as seeding trials, these studies prioritize marketing over science while disguising their commercial purpose as legitimate research. Pharmaceutical companies use them to familiarize physicians with new products under the guise of data collection. Participants sign consent forms, believing they are contributing to medical knowledge.

In reality, patients are absorbing risks that serve corporate interests rather than resolving genuine uncertainty about the therapeutic potential of a drug.

The term seeding trial first entered the medical literature in 1994, when then-commissioner of the Food and Drug Administration David Kessler and his colleagues described such studies as attempts to entice doctors to prescribe new drugs through trials that appear to serve little scientific purpose.

Three decades later, the problem of seeding trials persists.

How Seeding Trials Work

While the structure of a seeding trial looks similar to legitimate clinical trials on the surface, the objectives are different.

In a typical clinical trial, researchers recruit patients across clinics and hospitals to test whether a treatment is safe and effective.

In contrast, the pharmaceutical company behind a seeding trial enrolls large numbers of physicians at many sites, each seeing only a few patients. The goal is exposure: getting doctors to prescribe the drug, not generating robust data. Doctors may be selected based on their prescribing volume rather than their research credentials.

In a legitimate trial, the number of study sites reflects the number of patients needed to answer a scientific question. In a seeding trial, the number of sites reflects the number of doctors the company wants to reach.

Seeding trials often target drugs already on the market and operate as Phase 4, or postmarketing, studies. These types of studies are typically conducted after a drug has been approved to monitor its long-term safety or effectiveness. This trial stage receives less regulatory scrutiny than trials for initial drug approval, and the aims of the study may have limited relevance to actual patient care. 

For example, a seeding trial might measure whether patients prefer the taste of a new formulation or how quickly a drug dissolves in the stomach, rather than whether it actually improves health outcomes.

Legitimate trials also have independent oversight, with committees of scientists and ethicists who monitor the study’s progress and can halt it if patients are being harmed.

In a seeding trial, this oversight is often minimal. The sponsor of the study – typically the pharmaceutical company funding the research – maintains heavy control over the trial’s design and conduct.

Vioxx and Gabapentin Seeding Trials

Seeding trials had attracted little public attention until litigation in the 1990s forced open the internal files of two major pharmaceutical companies, revealing that studies presented as science had been designed as marketing campaigns.

The most notorious example is Merck’s ADVANTAGE trial for the painkiller Vioxx (rofecoxib), which was first approved in 1999. The company presented the study, which ran from 1999 to 2001, as scientific research, but internal documents revealed that its primary purpose was to encourage physicians to prescribe Vioxx to their patients.

Meanwhile, Merck was accused of downplaying the significant cardiovascular risks associated with the drug. The consequences were severe: Approximately 30,000 lawsuits and nearly $5 billion in compensation followed Vioxx’s withdrawal from the market.

Parke-Davis’ STEPS trial for the painkiller Neurontin (gabapentin) – first approved in 1993 for epilepsy – followed a similar pattern of disguising marketing as research. Internal documents showed that the trial, which ran from 1996 to 1998, aimed to disseminate marketing messages through the medical literature and encourage clinicians to prescribe the drug off-label for conditions it was not approved for, such as neuropathic pain and bipolar disorder.

Unlike Vioxx, gabapentin was never withdrawn. The trial’s commercial legacy outlasted its scientific one.

These cases came to light only because litigation forced the release of internal company documents. Without that exposure, they would have remained indistinguishable from ordinary research.

How Common Are Seeding Trials?

My team and I study how pharmaceutical firms innovate and respond to regulations. To estimate the prevalence of seeding trials, we analyzed nearly 34,400 industry-funded Phase 3 and Phase 4 studies that posted results on ClinicalTrials.gov between 1998 and 2024. 

The trials covered seven therapeutic areas where researchers had previously documented seeding trials, including major depressive disorder, epilepsy, Type 2 diabetes and rheumatoid arthritis.

We screened these trials for criteria that prior research has identified as hallmarks of a seeded trial, such as low patient-to-site ratios and limited independent oversight.

Ultimately, we identified 204 trials – 0.59% – that had characteristics consistent with marketing-driven study design. The prevalence of these probable seeding trials in different disciplines ranged from 0.15% in osteoarthritis to 0.98% in rheumatoid arthritis.

These figures might understate the true scope of marketing-driven research. The criteria we used capture only the most identifiable cases of studies driven by marketing purposes. Definitively identifying seeding trials requires access to internal sponsor documents revealing the intent of the study, and those documents surface only through litigation or whistleblowers.

Many trials occupy an ambiguous middle ground, generating useful data while simultaneously serving promotional objectives. Without systematic surveillance, the full extent of marketing-driven studies remains unknown.

The criteria to identify seeding trials also require careful interpretation. A low patient-to-site ratio, for instance, can reflect the practical difficulties of enrolling patients in studies of drugs already on the market, such as trials testing new drug combinations or new uses for an existing treatment. These markers are best understood as signals of possible marketing intent warranting closer scrutiny, not proof of marketing intent.

Whether the prevalence of seeding trials has shifted with the expansion of transparency requirements over the past decade cannot be determined from existing registry data.

What Can Be Done

Seeding trials may be uncommon, but they are not accidental. They reflect structural incentives in a system where the companies that fund research also stand to gain from its results. Strengthening transparency in clinical trial registration, funding disclosure and oversight would help ensure that clinical research serves patients first.

Along with other researchers, we’ve proposed reforms that cluster around two areas. The first is standardized reporting that discloses trial funding, investigator payments, enrollment criteria and the rationale for site selection. 

The second is independent oversight, such as committees funded through pooled industry levies, which are fees collected from pharmaceutical companies to finance independent monitoring. Random audits with publicly available results are one form of such oversight.

Some infrastructure for tracking financial relationships between industry and physicians is already in place. In the U.S., the Open Payments database allows public tracking of industry payments to physicians. But regulatory variability across countries creates openings for companies to conduct marketing-driven trials in jurisdictions with weaker oversight, particularly in low- and middle-income countries.

Clinicians can protect themselves and their patients by screening for a set of red flags before agreeing to participate in or cite a trial in their research. These include unusually low patient-to-site ratios, selecting investigators based on prescribing volume, sponsor-dominated oversight and study endpoints of limited clinical relevance. Consent forms are among the few documents patients see before enrolling, and clearer disclosure of the commercial and scientific purpose of a study is among the reforms we have called for.

For patients, clinicians and regulators alike, the question to ask of any trial is the same: Whom does it really serve?

Sukhun Kang, PhD, is an Assistant Professor of Technology Management at University of California, Santa Barbara.

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

Combining Opioids With a Cannabis-Based Medicine Doesn’t Add to Pain Relief

By Pat Anson

Combining a low dose of opioids with a cannabis-based medicine did not improve acute pain for people with arthritis, according to results of a small clinical study published in the journal Anesthesiology.

Animal studies have suggested that the two drugs might have a synergistic effect and provide better pain relief, but the study of 21 people with knee osteoarthritis found no added benefit. 

“Some patients believe combining cannabis with opioids can help with pain, and clinicians may recommend or prescribe it in states where cannabis is legal,” said lead author Katrina Hamilton, PhD, a Psychiatry Professor at Johns Hopkins School of Medicine. “Our study suggests that isn’t the case and patients may experience more side effects when the drugs are combined.”

There are some important caveats to the study that diminish its findings.

One is the design of the study and its small size – just 21 patients – who received placebo pills, hydromorphone alone, dronabinol alone, and a combination of hydromorphone and dronabinol. 

Participants received all four combinations prior to having pain induced by sticking their hands in cold water or having their skin rubbed with a “hot” capsaicin cream. That means the researchers were evaluating acute pain induced in a laboratory, not the chronic pain caused by arthritis.

Second, dronabinol (Marinol) is not cannabis. Dronabinol is a synthetic version of THC, the active ingredient in cannabis. It is FDA-approved to treat nausea and vomiting in chemotherapy patients, and to improve appetite in AIDS patients. Dronabinol was never intended to provide pain relief and has little in common with the various forms of cannabis (edibles, smoking, vaping) used in the real world. 

Third, while hydromorphone is a potent opioid, the oral dose (2 mg) that was used is relatively low – about 10 morphine milligram equivalents (MME). The research team had previously conducted a similar study using 4mg of hydromorphone. That also produced little pain relief for participants, so it’s not surprising that 2mg didn’t help either, although researchers say the lower dose has a “better safety profile.” 

The researchers found that taking hydromorphone and dronabinol, either alone or in combination, did not provide significant relief from acute pain. The opioid alone reduced pain sensitivity, while dronabinol did not, but neither meaningfully reduced participants’ self-reported pain.

When the two drugs were combined, side effects such as drowsiness, dizziness and impaired thinking were stronger and more noticeable, but without added pain relief.

“Opioid and cannabinoid medications failed to produce robust analgesia in experimentally induced pain among patients with knee osteoarthritis. In contrast to preclinical studies, there was no evidence of synergistic analgesic effects by combining hydromorphone and dronabinol,” researchers concluded.

While the dose of hydromorphone was low, the 10mg dose of dronabinol that was used in the study is a hefty amount. Interestingly, participants reported more of a “high” sensation from the dronabinol than from hydromorphone. But again, dronabinol is a synthetic version of cannabis and has little in common with what most cannabis consumers use.    

“In the real world, people often use cannabis differently, including lower starting doses, using gradually stronger doses, which may affect both benefits and side effects,” said Hamilton, acknowledging the limits of her study. “More research is needed to better understand how cannabis affects pain when used in real-world settings.”