Can Alcohol Help Treat Chronic Pain?

By Pat Anson, Editor

Treating chronic pain with a glass of wine or beer may not sound like a good idea, but an intriguing new study in the U.K. found that alcohol consumption is associated with lower levels of disability in pain patients.

Researchers at the University of Aberdeen in Scotland surveyed over 2,200 people with fibromyalgia and other chronic widespread pain conditions about their alcohol consumption. About a quarter of the respondents were teetotalers, the rest drank rarely, moderately or heavily – the latter consuming as much as 21 to 35 “units” of alcohol a week.

A “unit” was defined as 10 ounces of beer, a small glass of wine or a single beverage with hard liquor – meaning the heaviest drinkers averaged three to five drinks a day.

Drinkers overall reported less disability than people who never drank alcohol, but it was the heaviest drinkers who reported the least disability. They were 67% less likely to experience disability than the teetotalers.

“As well as an association between alcohol consumption and lower levels of disability in pain patients, we also found that the population prevalence of chronic pain was lower in drinkers than in non-drinkers. It’s clear that non-drinkers are more likely to have pain, and more likely to be disabled by it if they have it, compared to drinkers,” said Marcus Beasley, study coordinator at the University of Aberdeen.

Does alcohol act as an analgesic and simply dull pain sensations? Or does it treat and help prevent chronic pain? The researchers are cautious about drawing any conclusions.

“This study has demonstrated strong associations between level of alcohol consumption and CWP (chronic widespread pain). However the available evidence does not allow us to conclude that the association is causal. The strength of the associations means that specific studies to examine this potential relationship are warranted,” wrote Professor Gary Macfarlane, lead author of the study published in the journal Arthritis Care & Research.

“The design of this study cannot tell us whether drinking causes people to have less problems with pain, or if people who have pain make the choice not to drink. In any case people that drink are very different on a wide range of health measures than those that do not drink,” said Beasley.

“For primary care practitioners these findings mean that the fact a patient does not drink could be considered a potential marker for having other health problems, including with chronic pain. Otherwise, the advice that practitioners give to patients should remain the same – drink less if possible, and if consuming alcohol then do so within recommended safe limits.”

Previous research has linked moderate alcohol consumption with a lower risk of heart disease, stroke and diabetes. But drinking too much alcohol can lead to a variety of serious health problems.

How much is too much?

According to the Mayo Clinic, moderate alcohol consumption for healthy adults means up to one drink a day for women of all ages and men older than age 65, and up to two drinks a day for men age 65 and younger.

The UK study isn’t the first to find an association between alcohol and a reduced risk of chronic pain. A large study conducted in Sweden, published in the British Medical Journal, found that women who had more than three drinks a week had about half the risk of developing rheumatoid arthritis than non-drinkers.

Another study, published in Arthritis Research & Therapy, found that low and moderate drinkers suffering from fibromyalgia had less pain, less fatigue and missed fewer days of work than non-drinkers.

Marijuana Effective for Diabetic Neuropathy Pain

By Pat Anson, Editor

New research shows that inhaled medical marijuana can significantly reduce pain from diabetic neuropathy within minutes of treatment.

The study, published in The Journal of Pain, also found there was a dose dependent reduction in pain depending on the strength of marijuana used.

Researchers at the University of California San Diego followed 16 patients with diabetic peripheral neuropathy (DPN) in a double-blind study as they were exposed to low, medium and high doses of tetrahydrocannabinol (THC), the psychoactive compound in marijuana that makes people “high.”

Patients used a Volcano vaporizer to inhale marijuana with 1%, 4% and 7% THC, as well as a placebo. A vaporizer was used because it is less harmful than smoking and delivers THC into the bloodstream rapidly.

“We hypothesized that inhaled cannabis would result in a dose-dependent reduction in spontaneous and evoked pain with a concomitant effect on cognitive function,” said lead author Mark Wallace, MD, professor of anesthesiology, University of California San Diego School of Medicine. 

Results showed that the highest dose of THC reduced pain by nearly 70%, with the analgesic effect starting within minutes of inhaling and reaching its peak about an hour after treatment. The analgesic effect of the low and medium doses of THC was slightly lower.

All of the patients experienced either euphoria or somnolence, regardless of the dose, with modest effects on attention, memory and impairment.

“These findings along with previous studies suggest that cannabis might have analgesic benefit in neuropathic pain syndromes, including treatment-refractory DPN,” said Wallace.

Nearly 26 million people in the United States have diabetes and about half have some form of neuropathy, according to the American Diabetes Association.  Diabetic peripheral neuropathy causes nerves to send out abnormal signals. Patients feel burning, tingling or prickling sensations in their toes, feet, legs, hands and arms.

There are only two drugs approved by the Food and Drug Administration to treat DPN -- Cymbalta and Lyrica – and many patients say they don’t work or have unpleasant side effects.

Marijuana Helps Heal Broken Bones

Meanwhile, researchers in Israel have discovered that a compound in marijuana can help heal fractures and rebuild bones.

In an animal study published in the Journal of Bone and Mineral Research, researchers at Tel Aviv University reported that cannabinoid cannabidiol (CBD) – a non-psychoactive ingredient in marijuana – significantly enhanced the healing process in rats with broken legs.

Earlier studies by the same research team found that cannabinoid receptors in the human body stimulate bone formation and inhibit bone loss. The findings suggest that cannabinoid based drugs could be used to treat osteoporosis and other bone-related diseases.

"The clinical potential of cannabinoid-related compounds is simply undeniable at this point," said Dr. Yankel Gabet of the Bone Research Laboratory at the Department of Anatomy and Anthropology at Tel Aviv University.

The researchers injected one group of rats with CBD alone and another with a combination of CBD and THC. They found that CBD by itself provided the most therapeutic benefit.

"We found that CBD alone makes bones stronger during healing, enhancing the maturation of the collagenous matrix, which provides the basis for new mineralization of bone tissue," said Gabet.

"Other studies have also shown CBD to be a safe agent, which leads us to believe we should continue this line of study in clinical trials to assess its usefulness in improving human fracture healing.”

Most Pain Patients Use Alternative Therapy (Video)

By Pat Anson, Editor

A large new study of chronic pain patients found that over half were using chiropractic care or acupuncture for pain relief, but many didn’t discuss their use of alternative therapy with their primary care providers.

Researchers surveyed over 6,000 patients in Oregon and Washington State who were Kaiser Permanente members and had three or more outpatient visits for chronic pain in 18 months.

The study, published in the American Journal of Managed Care, found that 58 percent of the patients had used chiropractic care, acupuncture, or both.

Over a third (35%) of the pain patients who had acupuncture never told their doctor, while 42% who had chiropractic care didn't talk to their providers about it. Almost all of the patients said they would be happy to share this information if their doctor had asked.

"Our study confirms that most of our patients with chronic pain are seeking complementary treatments to supplement the care we provide in the primary care setting," said Charles Elder, MD, lead author of the study and affiliate investigator at the Kaiser Permanente Center for Health Research. "The problem is that too often, doctors don't ask about this treatment, and patients don't volunteer the information.

"We want our patients to get better, so we need to ask them about the alternative and complementary approaches they are using. If we know what's working and what's not working, we can do a better job advising patients, and we may be able to recommend an approach they haven't tried,” said Elder, who is the lead physician for Kaiser Permanente's complementary and alternative medicine program.

The majority of the patients in the study (71 percent) were women, and the mean age was 61. Most suffered from back pain, joint pain, arthritis, neck and muscle pain, or headache.

The study was funded by a grant from the National Center for Complementary and Integrative Health.

A video report on the study that was produced by Kaiser Permanente can be seen here:

One-hundred million Americans suffer from chronic pain every year, and many of them turn to alternative therapies for relief. In fact, a new study shows that more than half of patients with chronic pain enrolled in a managed care setting use chiropractic care or acupuncture.

How Does Your Surgeon Rate?

By Pat Anson, Editor

Before the Internet age, finding a good doctor usually depended on word-of-mouth referrals and recommendations -- or just sheer luck.

Now there are over a dozen online resources to help patients find physicians in all sorts of medical specialties, from oncology and neurology to podiatry and psychology.

The latest is Surgeon Scorecard, a searchable database put together by the non-profit ProPublica, that estimates complication rates for nearly 17,000 doctors who perform one of eight elective surgeries, including neck and lumbar spinal fusions, as well as hip and knee replacements.

The database – which uses government records collected from Medicare patients – can be searched by location, hospital or surgeon to learn how they performed during these “routine” procedures -- and whether they had complications such as infections, blood clots, internal bleeding or worse.

“It’s long overdue,” Dr. Charles Mick, a former president of the North American Spine Society told ProPublica. “Hopefully, it will be a step toward a culture where transparency and open discussion of mistakes, complications and errors will be the norm and not something that’s hidden.”

ProPublica found that even the best hospitals had surgeons with higher than average complication rates – and that selecting the right doctor could be a matter of life or death. Over 200,000 hospital patients die every year from preventable errors and complications.

Overall, complication rates are low for most surgeons – just 2 to 4 percent depending on the procedure – but a small share of doctors (11%) are responsible for about 25% of the complications. Hundreds of surgeons have complication rates double and triple the national average.

One such doctor is Constantine Toumbis, a surgeon at Citrus Memorial Hospital in Inverness, Florida. The “Surgeon Scorecard” shows that at least 27 of Toumbis’ patients have either died or suffered serious complications after surgery.

One patient died just days after a spinal fusion -- even though Toumbis had written in her records that the operation went well, according to ProPublica. An autopsy proved otherwise, when the medical examiner found bone fragments in the patient’s neck and signs of an extensive hemorrhage.

Toumbis and Citrus Memorial both declined to comment to ProPublica about the case.

Patient Resources

In addition to the "Surgeon Scorecard," several other searchable databases can be found in the “Patient Resources” section of this website that can help you find a good doctor, healthcare facility or the right treatment.

Vitals can help you locate a doctor with a specific specialty anywhere in the United States, along with patient reviews of that physician.

RateMDs has patient reviews of over a million doctors and healthcare facilities, including some outside the United States.

Healthgrades uses an extensive database and patient reviews to rate doctors based on their experience, complication rates and patient satisfaction.

The Centers for Medicare and Medicaid Services has a database that reveals if your doctor received money from a drug maker or medical device company for consulting, travel expenses, meals, research and promotional services.

Iodine has been called the "Yelp of Medicine." It uses patient reviews to rate the quality, efficacy and side-effects of prescription drugs, including opioid painkillers.

Healthcare Bluebook helps consumers save money on medical expenses -- everything from drugs to surgery to x-rays -- by giving them access to a nationwide database that estimates a "fair price" for whatever they're paying for.

Is Cinnamon a Safer Pain Reliever?

By Pat Anson, Editor

A new warning from the U.S. Food and Drug Administration about the risk of serious side effects from non-steroidal anti-inflammatory drugs (NSAIDs) may have you thinking about finding safer, more natural pain relievers.

The idea isn’t new by any means – about 2,400 years ago the Greek physician Hippocrates was writing about the use of willow bark to ease aches and pains. Other natural remedies used for centuries to relieve pain and reduce inflammation include St. John’s Wort, ginger, ginseng, turmeric, and cinnamon.

Cinnamon, in fact, was recently found to be nearly as effective as the NSAID ibuprofen in relieving pain from menstrual cramps (dysmenorrhea).

The results of a small double-blind clinical trial, published in the Journal of Clinical and Diagnostic Research, evaluated the effects of cinnamon, ibuprofen and a placebo in 114 Iranian female college students. The women were broken up into groups of three; and given either 420 mg of Cinnamon Zeylanicum, 400 mg of ibuprofen or a starch placebo during the first 72 hours of their menstrual cycle.

Eight hours after treatment, researchers found that pain severity in the cinnamon group was significantly less than those who took a placebo, while pain severity in the ibuprofen group was less than those who took cinnamon.

Although ibuprofen was found to be the more effective pain reliever, the researchers believe cinnamon may be a better treatment for menstrual cramps because it doesn’t have the side effects of ibuprofen.

“The research results suggest that, Cinnamon as compared significantly reduces the severity and duration of pain during menstruation, but this effect is less compared to that of Ibuprofen. Due to the lack of adverse events in this study, Cinnamon can be used as a safe and non-pharmacological treatment for primary dysmenorrheal pain in young girls,” the researchers reported.

Iranian researchers have also found that thyme oil and lavender oil were effective in treating menstruation cramps, according to GreenMedInfo.

Last week, the FDA warned that "everyone may be at risk" from using NSAIDs – and ordered drug makers to strengthen warning labels about the risk of a fatal heart attack or stroke.

The warning applies to Advil, Tylenol, Motrin and other popular pain relievers sold over-the-counter, as well as all prescriptions drugs containing ibuprofen and acetaminophen. Many multi-symptom cold and flu products, such as NyQuil and DayQuil, also contain NSAIDs.

The agency said studies have shown the risk of serious side effects can occur in the first few weeks of using NSAIDs and could increase the longer people use the drugs. The revised warning does not apply to aspirin.

Searching for Medical Marijuana’s ‘Therapeutic Window’

Dr. Mark Ware is one of the world’s leading experts on medical marijuana. Ware is an associate professor in Family Medicine and Anesthesia at McGill University in Montreal and director of clinical research at the Alan Edwards Pain Management Unit at McGill University Health Centre. He practices pain medicine at Montreal General Hospital.

Although medical marijuana is legal throughout Canada, and in 23 U.S. states and the District of Columbia, mainstream medicine still frowns upon its use. Research into the therapeutic benefits of cannabis -- particularly for pain management -- has also been limited.

Pain News Network editor Pat Anson recently spoke with Ware at the annual meeting of the American Pain Society. The interview has been edited for content and clarity.

DR. MARK WARE.

Anson: You’ve called medical marijuana an “incredible social experiment.” What do you mean by that? 

Ware: I think what we’re seeing is the lid coming off something that’s been going on for a long time. I think people have been self-experimenting with marijuana for years and years. People have been growing it in their basements and backyards. So there’s been a social experiment with cannabis since the 1960’s in the Western world.

I think the medical aspect of it has kind of followed through with that, because as you get thousands of people using cannabis, eventually somebody with an illness is going to stumble upon it. Lester Grinspoon (a marijuana researcher) reported on this in 1971. So that’s how long we’ve known or suspected the potential medical properties. The fact that the drug has been illegal has suppressed the possibility of there being much in the way of good quality research. So the experiment has been going on underground, out of sight and out of the public eye.

What we’re seeing now is that suddenly we’re able to talk about it. We’re able to look at this seriously. And we’re beginning to realize how much was already going on. So I think it’s an experiment that’s been going on for a long time and we’re beginning to put some parameters around it now, which allow us to track it more carefully. And hopefully it can yield some important results that can help inform the patient and the physician about what to do with this.

Anson: Some doctors have told me they don’t think marijuana will ever go mainstream until big companies like Pfizer and Purdue Pharma start backing marijuana research and doing clinical studies. Would you agree with that?

Ware: I don’t know if I would agree with that. That’s true for new pharmaceutical drugs. If you’re developing a molecule from the lab up, you need Big Pharma to come along and take that and move it to the point where they can do the big clinical trials.

With an herbal medicine, I think you almost don’t want to look at the pharmaceutical model for drug development. It’s more like how we regulate natural health products in Canada. We want good quality cultivation techniques, we want good quality processing, and we want to know what it is that we’re giving to patients.

I think fundamentally what we have to figure out is what we want to know about this drug. What is it that we need to know and how do we go about getting that information?

I think if we wait for Big Pharma to come along it’s going to be a long wait.  They would have been on this long ago if they thought this was important.

It’s a plant based medicine that’s already in our society at some level and we need to recognize the reality that mainstream doesn’t mean mainstream prescription availability. It’s going to mean mainstream figuring out how to put cannabis in a safe place in our society.

Anson: Medical marijuana is so widely available today, it’s like we’re already past the clinical trial phase.

Ware:  Exactly.  And to go back and do the Phase III study now, it’s expensive and would take hundreds of millions of dollars. And that requires knowing whether you’re going to get your money back. Companies invest that money when they know they’ve got a patent and they can make money back on the drug in the ten years after it’s launched. It’s much harder to see that happening with an herbal material like cannabis.

Why invest the money? It’s already available. You can already buy it at the dispensary. So now the question is how do we improve that process? How do we improve the quality of the product? How do we label them so people know what’s in them? How do we provide information to the patients that are buying them? What they should be looking for and what they should be careful about?

And how do we inform the physicians and health professionals who should be managing that whole process or at least informing it? What kinds of patients should be avoiding this? This isn’t for young kids. This isn’t for women who are pregnant. Some of this is obvious, but some of it needs to be specified and mandated.

I don’t think there’s strong enough evidence to start using cannabis in younger people. I think that the risks of cannabis on the developing brain in teenagers is significant enough that, unless there is a very real reason like a younger person with a severe intractable illness, this is a drug that should be held for the 25 and older crowd.

I would caution people who have unstable heart problems against using cannabis. It does increase your heart rate, can open up your blood vessels, and that could precipitate some heart problems.

Anson: What are the pain conditions that you think medical marijuana can be beneficial for?

Ware: I think for sure it’s more likely effective for chronic pain than acute pain. It’s never been reported for acute pain syndromes, but it has been reported for chronic pain.  There are clinical trials now that bear out that chronic neuropathic pain is one of the relieved conditions that it seems to respond to. We’ve seen reports for spinal cord injury, fibromyalgia, and PTSD (post-traumatic stress disorder). Cannabinoids appear to have some signals in some of these conditions.

And then you go beyond that to abdominal pain with Crohn’s disease, diabetic neuropathy, and so on. The list of conditions where it looks like it may work is as long as your arm.  There are individual case reports of cannabis being used on a huge range of conditions.

Anson: What is the most effective delivery system? Everyone thinks of smoking, but there are plenty of other ways to ingest marijuana.

Ware: There are. And I think the key thing is the difference between inhaling and taking it by mouth. The inhaled route is a very quick onset, has a very rapid effect on the patient, and then a fairly quick half-life; whereas the oral route takes much longer to absorb and takes a longer time for the patient to feel the effects. But then it lasts a lot longer. 

courtesy drug policy alliance

So it’s almost like a short acting versus a long acting medication. I don’t think there’s any way of saying one is more effective than the other. I think they’re effective in different ways.

If I was vomiting because of chemotherapy, I’d want something I could inhale to control the vomiting quickly. But if I’m not able to sleep because of my chronic pain, I want something that would be longer lasting so I could sleep through the night.  I don’t want to wake up three hours later and have to do it again. So I think we just have to figure out how to use the different administrative techniques for different clinical conditions.

Anson: Most of our readers are pain patients and when this subject comes up many of them say, “I’ve never tried marijuana. I’m curious about it and I’d like to try it, but I’m worried about getting high.” Can they get pain relief without getting high?

Ware: We’ve done studies where we kept the doses very, very small -- to the point where people have read the protocols and said you’re not giving these patients enough to feel the effect. And in fact, what happens is patients are still able to find analgesic benefit and avoid that euphoric or psychoactive effect.

That’s important for most patients. They want to be able to use a drug or any kind or a therapy that doesn’t impair them from doing the things that they need to do. They need to drive. They need to work. They need to hang out with their families. They need to do their sports and their activities. And this is part of pain management generally. We want people to be living as full and as active a life as possible. We don’t want them collapsing on the couch all day long.

So can we find that window, what we call that therapeutic window, that dose where you get the benefit but you don’t get the sedative or psychoactive effect? And I think we can. I think for patients who are considering this approach, they really have to learn to be very patient and use very, very small doses. Try very small amounts first and allow your body to feel what the drug is doing to you. And if nothing happens, that’s okay. You’ve started with a low enough dose that you felt nothing. You gradually work your way up.

The interesting thing about cannabis is that there are two ways of thinking about dose. One is the amount of the drug itself, the number of grams, joints or pipes, if you will. The other is the THC level of the cannabis itself.

courtesy drug policy alliance

If patients have access to material where the THC level has been standardized or has been measured, they should be trying to use THC cannabis that is as low as possible, because the likelihood of having a psychoactive reaction to a high THC cannabis is much higher.

If it’s high in THC, it doesn’t take much to get that effect, where if they use very low THC levels, less than 10 percent THC, and they use a small quantity of the material, then potentially they can find that therapeutic window that can be effective.

Anson: What about taking marijuana with opioids? Can you do that?

Ware: You can. There’s no medical reason why you shouldn’t. I think the key thing for patients who are doing that, and again I emphasize with the knowledge and support of their physician, is that they can reduce the doses of other medications which may not be helping as much.

Cannabis use can be seen in terms of improving patients in two ways. One is in reducing the medications that they’re already taking, which may have side effects. And the other is in improving their functioning state so that they’re doing more. This is where I think the responsibility lies with the patient to prove to the doctor that this drug is helping. And you do that by reducing your other medications with the doctor’s support, by increasing your functioning and by showing that you’re doing things that you weren’t doing before. That is what doctors want to see.

There appears to be evidence, at least in animal studies, that opioids and cannabinoid drugs work synergistically. So if you take the two separately and you take the two combined, you get a greater effect with the combination than if you took either of the others by themselves.

This synergism, we’ve seen it in patients who started using cannabis successfully and they were able to reduce their other medications. In some cases they find that the dose of opioids they were taking, they can lower it and get a similar effect with much lower doses. With others, they don’t need the opioids any longer and they can taper off it and stop completely. 

Anson: One fear of using medical marijuana is that it could make you more prone to abusing other substances.

Ware: I think patient selection is very important when you’re considering as a physician whether to authorize or prescribe cannabis, because cannabis is a drug with a known risk of abuse and dependence by itself. There are people who struggle with their marijuana use and withdrawal when they try to get off it. Physicians need to be sure they’re not making things worse for a patient that has a dependency disorder by authorizing cannabis.

Screening for dependence means looking for abuse of other substances, such as alcohol. If you’ve done that carefully, prescribing cannabis to a patient who doesn’t have that addiction risk appears to be fairly safe.

Medical cannabis should be used as an option only when all the conventional therapies have failed; when all of the other approaches to pain management, and I’m not just talking about pharmacology, but when all of the non-pharmacological approaches have all been considered and tried. Cannabis is not at the point where it can be thrown in as a first line agent for a patient struggling with pain management.

Anson: Thank you, Dr. Ware.

Childhood Trauma Linked to Adult Migraine

By Pat Anson, Editor

Children who witness domestic violence between their parents are significantly more likely to experience migraine headaches as adults, according to a large new study published in the journal Headache.

Researchers at the University of Toronto examined a nationally representative sample of over 12,000 women and 10,000 men who participated in the 2012 Canadian Community Health Survey-Mental Health. About 6.5% of the men and 14.2% of the women experienced migraine, which is consistent with prior research.

Participants were asked if they had experienced three types of childhood trauma: physical abuse, sexual abuse or if they witnessed parental domestic violence.

"We found the more types of violence the individual had been exposed to during their childhood, the greater the odds of migraine. For those who reported all three types of adversities -- parental domestic violence, childhood physical and sexual abuse -- the odds of migraine were a little over three times higher for men and just under three times higher for women" said Sarah Brennenstuhl, PhD, first author of the study.

Researchers said the most surprising finding was the link between migraines and parental domestic violence. Even after accounting for variables such as age, race, and socioeconomic status, men and women who had witnessed parental domestic violence had 52% and 64% higher odds of migraine compared to those who did not see their parents fighting.

"The cross-sectional design of our study does not allow us to determine if the association between early adversities and migraines is causative, but our findings do underline the importance of future prospective studies investigating the long-term physical health of children exposed to parental domestic violence,” said co-author Esme Fuller-Thomson, professor and Sandra Rotman Endowed Chair at University of Toronto's Factor-Inwentash Faculty of Social Work.

Previous research by Fuller-Thomson has found that depression and thoughts of suicide are more likely among individuals with migraine.

The risk of depression and suicide ideation is about twice as high for those who experience migraine. Individuals with migraine who are under the age of 30 had six times the odds of depression compared to migraineurs aged 65 and over.

Migraine is thought to affect a billion people and about 36 million adults in the United States, according to the American Migraine Foundation. It affects three times as many women as men. In addition to headache pain and nausea, migraine can also cause vomiting, blurriness or visual disturbances, and sensitivity to light and sound. About half of people living with migraine are undiagnosed.

The month of June is Migraine Awareness Month.

Study Finds ‘Moderate' Evidence Marijuana Treats Pain

By Pat Anson, Editor

The American Medical Association, the nation’s largest medical group, still officially considers medical marijuana “a dangerous drug and as such is a public health concern."

But studies being published this week in JAMA, the AMA’s official journal, highlight the slim but growing body of evidence that cannabis can be used to treat pain – as well as the lack of standards regulating medical marijuana in states where it is legal.

In a review of nearly 80 clinical trials involving over 6,400 patients, researchers found “moderate-quality evidence” that cannabinoids –  chemically active compounds in marijuana – are effective in treating chronic neuropathic pain and cancer pain, as well as muscle spasms and stiffness caused by multiple sclerosis.

There was “low-quality evidence” suggesting that cannabinoids are effective in treating sleep disorders, weight loss, Tourette syndrome, and symptoms of nausea and vomiting caused by chemotherapy; and “very low-quality evidence” for treating anxiety.

Some of the side-effects associated with medical marijuana were dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.

"Further large, robust, randomized clinical trials are needed to confirm the effects of cannabinoids, particularly on weight gain in patients with HIV/AIDS, depression, sleep disorders, anxiety disorders, psychosis, glaucoma, and Tourette syndrome are required. Further studies evaluating cannabis itself are also required because there is very little evidence on the effects and AEs (adverse events) of cannabis," the authors write.

An accompanying editorial in JAMA also called for more research and lamented the lack of evidence supporting the legalization of medical marijuana in 23 U.S. states and the District of Columbia.

"If the states' initiative to legalize medical marijuana is merely a veiled step toward allowing access to recreational marijuana, then the medical community should be left out of the process, and instead marijuana should be decriminalized," wrote Deepak Cyril D'Souza, MD, and Mohini Ranganathan, MD, of the Yale University School of Medicine.

"Conversely, if the goal is to make marijuana available for medical purposes, then it is unclear why the approval process should be different from that used for other medications… Since medical marijuana is not a life-saving intervention, it may be prudent to wait before widely adopting its use until high-quality evidence is available to guide the development of a rational approval process."

The Trouble with Edibles

A second study published in JAMA looked at marijuana edibles – cookies, brownies, candies and other foods containing cannabis – that are being sold at dispensaries in Los Angeles, San Francisco and Seattle.

An estimated 16% to 26% of cannabis patients consume edibles. Many are essentially homemade products that vary from dispensary to dispensary.

Researchers found that many of the edibles had lower amounts of THC (tetrahydrocannabinol) – the active ingredient in marijuana that makes people “high” – than their labels indicated. Over half had significantly higher amounts of THC, putting patients at risk of unintended side-effects.

Of the 75 edible products that were analyzed in a laboratory, only 17% were accurately labeled with THC, 23% were “overlabeled” and 60% were “underlabeled.” The greatest likelihood of obtaining an underlabeled edible was in Seattle.

A little over half (59%) of the edibles tested had detectable levels of cannabinoids.

"Edible cannabis products from 3 major metropolitan areas, though unregulated, failed to meet basic label accuracy standards for pharmaceuticals," the authors write. "Because medical cannabis is recommended for specific health conditions, regulation and quality assurance are needed."

The lack of regulation was highlighted last year in Colorado – where both medical and recreational use of marijuana is legal. A brand of brownie mix, Rice Krispy treats and candy made with cannabis was recalled after inspectors found the edibles contained marijuana that had been “cleaned” in a washing machine.

New Drugs Could Relieve Neuropathy Pain

By Pat Anson, Editor

After more than a decade of study, researchers at Boston Children’s Hospital are close to developing a new class of non-narcotic drugs that relieve chronic nerve pain by targeting a protein that enhances pain and inflammation.

Their findings, reported in the journal Neuron, could lead to new treatments for diabetic peripheral neuropathy, post-herpetic neuralgia, and inflammatory diseases like rheumatoid arthritis. Current treatments provide meaningful pain relief in only about 15 percent of patients.

"Most pain medications that have been tested in the past decade have failed in Phase II human trials despite performing well in animal models," notes Clifford Woolf, MD, PhD, director of Boston Children's F.M. Kirby Neurobiology Center and a co-senior investigator on the study. "Here, we used human genetic findings to guide our search from the beginning."

Previous research by Woolf and his colleagues found that people with variants of the gene for GTP cyclohydrolase (GCH1) -- about 2 percent of the population -- are at markedly lower risk for chronic pain. GCH1 is needed to synthesize the protein tetrahydrobiopterin (BH4), and people with GCH1 variants produced less BH4 after a nerve injury. This suggested that BH4 regulates pain sensitivity.

To test their theory, researchers took a "reverse engineering" approach in genetic experiments on mice.  First they showed that mice with severed sensory nerves produce excess BH4, created by the injured nerve cells and by macrophages-- immune cells that infiltrate damaged nerves and inflamed tissue.

Mice that were genetically engineered to make excess BH4 had heightened pain sensitivity even when they were uninjured. Conversely, mice that were genetically unable to produce BH4 had lower pain hypersensitivity after a peripheral nerve injury.

"We then asked, if we could reduce production of BH4 using a drug, could we bring about reduction of pain?" said Alban Latremoliere, PhD, also of Boston Children's Kirby Center, who led the current study.

The answer was yes. The researchers blocked BH4 production using a specifically designed drug that targets sepiapterin reductase (SPR), a key enzyme that makes BH4. The drug reduced the pain hypersensitivity induced by nerve injury and without any detectable side effects.

Because BH4 plays an important role in the brain and blood vessels, the goal of any treatment would be to dial down excessive BH4 production, but not eliminate it entirely. Latremoliere showed that blocking SPR still allowed minimal BH4 production through a separate pathway and reduced pain without causing neural or cardiovascular side effects.

"Our findings suggest that SPR inhibition is a viable approach to reducing clinical pain hypersensitivity," says Woolf. "They also show that human genetics can lead us to novel disease pathways that we can probe mechanistically in animal models, leading us to the most suitable targets for human drug development."

Doctors Prescribing Opioids for Migraine Despite Risks

By Pat Anson, Editor

Physicians are still prescribing opioid painkillers or barbiturates to treat migraine, even though frequent use of the drugs can make headaches worse and raise the risk of addiction.

Over half the patients who visited a headache center in New York City said they had been prescribed opioids and/or barbiturates, according to a new study presented at the annual scientific meeting of the American Headache Society. About 20 percent of the 218 patients surveyed, most of whom had a migraine diagnosis, said they were still taking the drugs.

"Headache specialists are often in a difficult position when patients request opioids or increasing quantities of barbiturates," said lead author Mia Minen, MD, Director of Headache Services at NYU's Langone Medical Center. "Although many patients find these effective, they are known to contribute to headaches related to medication overuse."

Minen and her research team identified which physicians were prescribing the drugs and found the most frequent first prescribers of opioids were emergency room physicians, while general neurologists were the most frequent first prescribers of barbiturates. Primary care physicians were also identified as first prescribers.

"Taken as a whole, these data provide a useful snapshot of the wide variety of physician specialties that might benefit from additional education on the appropriate use of opioids and barbiturate-containing medications in patients with headaches," said Minen.

Opioids and barbiturates should only be used as a last resort to treat migraine, according to the American Board of Internal Medicine's "Choosing Wisely" campaign. The campaign recommends the first medications for migraine should be either over-the-counter pain relievers or a class of prescription drugs called triptans that are made specifically for migraine.

"This study underscores the fact that prescribers may not be aware of best practices in migraine care,” said Beth Darnall, PhD, a pain psychologist, clinical associate professor at Stanford University and author of Less Pain, Fewer Pills.

“Problems arise when ‘crisis solutions’ are applied as the de facto treatment for daily management of pain. Patients may believe that opioids are beneficial but they lead to worse migraine and headache pain, and are not considered appropriate first-line treatment for these conditions. If possible, patients should seek a specialized evaluation with a board certified specialist to ensure they receive medications that will help them in the long run.”

Darnall called opioids and benzodiazepines “a dangerous combination of medications,” and said they should be avoided or combined only under close medical supervision.

The problem extends far beyond the borders of the United States. According to the recently released Global Burden of Disease Study, the number of headaches caused by medication overuse has risen by 120% since 1990. Medication overuse headache is the 18th leading cause of disability worldwide.

New “Landmark” Class of Migraine Drugs Being Developed

Meanwhile, clinicians and researchers at the American Headache Society’s annual meeting are reportedly excited about a new class of drugs called Calcitonin Gene-Related Peptide (CGRP) monoclonal antibodies, which are showing promise in treating high-frequency episodic migraine and chronic migraine. Research studies on CGRP are being presented at the meeting, which draws more than 1,000 migraine specialists from around the world.

"This development is a transformative moment in migraine treatment," said Peter Goadsby, MD, who is chief of the UC San Francisco Headache Center and one of the world's leading headache treatment experts. "Up till now, migraine patients have had limited choices for preventive treatment. Now four pharmaceutical companies are showing positive results in human trials targeting CGRP mechanisms."

The new drugs appear to reduce elevated levels of the peptide known as calcitonin gene-related peptide, which is a key driver of migraine pain. Versions of anti-CGRP therapies are being tested by Alder Pharmaceuticals, Amgen, Eli Lilly and Teva Pharmaceuticals.

Teva reported that in a Phase II clinical study its CGRP therapy achieved a significant reduction in the number of headache hours after one week, with more than half of patients experiencing a 50% or greater reduction in headache frequency.

Amgen’s research showed showed that its anti-CGRP product also reduced the number of migraine days by 50% in about half the treated patients after 12 weeks.

"The potential of these new compounds is enormous and gives us real hope that effective specific treatments for migraine may be on the near horizon," said Goadsby. "The development of CGRP antibodies offers the simple, yet elegant and long awaited option for migraine patients to finally be treated with migraine preventives; it's a truly landmark development."

There has not been a new class of anti-migraine drugs since the development of triptans in the early 1990s.

Migraine is thought to affect a billion people and about 36 million adults in the United States, according to the American Migraine Foundation. It affects three times as many women as men. In addition to headache pain and nausea, migraine can also cause vomiting, blurriness or visual disturbances, and sensitivity to light and sound. About half of people living with migraine are undiagnosed.

The month of June is Migraine Awareness Month.

Chronic Fatigue Patients ‘Disrespected and Rejected’

By Pat Anson, Editor

An independent panel convened by the National Institutes of Health is calling for major changes in the way the healthcare system treats people suffering from chronic fatigue – a complex and poorly understood disorder that affects an estimated one million Americans, most of them women.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by extreme fatigue, chronic pain, impaired memory, insomnia, and other symptoms that do not improve with rest.  Many of the symptoms overlap with other diseases and disorders -- including fibromyalgia, depression, and inflammation – making a correct diagnosis even more difficult.

There is also a stigma often associated with chronic fatigue.

“Both society and the medical profession have contributed to ME/CFS patients feeling disrespected and rejected. They are often treated with skepticism, uncertainty, and apprehension and labeled as deconditioned or having a primary psychological disorder,” the panel states in its final report.

“ME/CFS patients often make extraordinary efforts at extreme personal and physical costs to find a physician who will correctly diagnose and treat their symptoms while others are treated inappropriately causing additional harm.”

Although the economic burden of chronic fatigue is estimated at between $2 billion and $7 billion annually, the panel said there has been “minimal progress” in improving the state of science for ME/CFS over the last 20 years. There are no pathogens linked to chronic fatigue, no diagnostic tests and no known cures.

"We need to learn more about the cellular and molecular mechanisms of this disease and how immunologic, neurologic, and other factors contribute to ME/CFS," said Carmen Green, MD, the panel’s chair and professor of anesthesiology, obstetrics and gynecology, and health management and policy at the University of Michigan Schools of Medicine and Public Health.

"We need to fund more studies that can be easily reproduced, and we must gain a better understanding of how ME/CFS affects people and their families in terms that are clinically meaningful to them. In addition, we need to have a greater understanding of the impact of ME/CFS across the life span, especially in underserved and vulnerable populations."

What little research that has been done has focused on Caucasian, middle-aged women.  The panel said new studies need to include children, minorities, men, patients living in rural areas, and those who are homebound.

To address these knowledge gaps, the panel is calling for more research and opportunities for new investigators to study ME/CFS. It also called for the creation of a repository of biological samples from chronic fatigue patients (e.g., serum, whole blood, RNA, DNA) to support new studies.

In addition, the panel recommended new educational training courses to help health care providers diagnose and treat ME/CFS.

"ME/CFS exists, and despite the absence of a clear definition, an estimated one million Americans are affected by it," said Green. "In order to develop primary prevention strategies and effective drug treatments, there needs to be a clear understanding of its causes and the populations it affects."

Much of the information gathered by the panel came during a public workshop and public comment period in December of last year. The five member panel, which included Penney Cowan of the American Chronic Pain Association, operated as an independent commission. Its final report is not a policy statement of the NIH or the federal government, and there are no guarantees its recommendations will be funded or acted upon.

Value of Arthroscopic Knee Surgery ‘Inconsequential’

By Pat Anson, Editor

Arthroscopic knee surgery on older adults has become a routine procedure in North America and Europe – with over 850,000 arthroscopies performed every year to relieve knee pain in the UK and the United States alone.

But a new study published in the The BMJ questions the evidence behind the procedure and calls the benefit of knee surgery “inconsequential.” The article is part of The BMJ's “Too Much Medicine” campaign, which highlights the waste of resources and potential harm caused by unnecessary medical care.

“The small inconsequential benefit seen from interventions that include arthroscopy for the degenerative knee is limited in time and absent at one to two years after surgery,” the report says. “Taken together, these findings do not support the practice of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis.”

Knee arthroscopies are a type of “keyhole” surgery in which the surgeon makes a small incision in the knee and inserts a tiny camera and instruments to diagnose and repair damaged ligaments or torn meniscus. Many specialists are convinced of the benefits of the surgery.

But when researchers in Denmark and Sweden reviewed 18 studies on arthroscopic knee surgery, they found that half were of poor quality or lacked a placebo control. The other nine studies found that the surgery provided pain relief for up to six months, but without any significant benefit in physical function.

Risks associated with arthroscopic knee surgery, although rare, include deep vein thrombosis (DVT), infection, pulmonary embolism, and death.

"It is difficult to support or justify a procedure with the potential for serious harm, even if it is rare, when that procedure offers patients no more benefit than placebo," argues Professor Andy Carr from Oxford University’s Institute of Musculoskeletal Sciences in an accompanying editorial.

With rates of knee surgery at their current level, Carr says thousands of lives could be saved and DVTs prevented each year if the procedure was discontinued or diminished.

“We may be close to a tipping point where the weight of evidence against arthroscopic knee surgery for pain is enough to overcome concerns about the quality of the studies, confirmation bias, and vested interests. When that point is reached, we should anticipate a swift reversal of established practice,” Carr wrote.

The BMJ study is not the first to question the value of arthroscopic knee surgery.  A 2014 report by a German health organization found the procedure provides no benefit to patients with osteoarthritis, and does not relieve pain any better than physical therapy or over-the-counter pain medications.

Another large study in Australia also questions the value of arthroscopic knee surgery, finding there was no significant benefit for osteoarthritis patients.

The American Medical Society for Sports Medicine (AMSSM) lists arthroscopic knee surgery as one of five procedures that are not always necessary in the Choosing Wisely campaign. The AMSSM advises physicians to avoid recommending knee arthroscopy as a treatment for patients with degenerative meniscal tears.

Depending on insurance, hospital charges and the surgeon, arthroscopic knee surgery costs about $4,000.

Aleve & Other Pain Relievers Reduce Fertility in Women

By Pat Anson, Editor

Health experts have warned for years about the side effects of over-the-counter pain relievers – everything from liver failure to heart disease to hearing loss.

Now researchers are saying that Aleve and some other non-steroidal anti-inflammatory drugs (NSAIDs) reduce the fertility of women so significantly they could potentially be used as an emergency form of contraception.

The results of a small study presented at the European League Against Rheumatism Annual Congress show that three NSAIDs --  naproxen, diclofenac, and etoricoxib -- inhibited ovulation in women after just a few days of treatment.

Naproxen, diclofenac, and etoricoxib are the active ingredients in several brand name drugs sold around the world, including Aleve, Voltaren, and Arcoxia, respectively. Etoricoxib is not approved for use in the United States.

Thirty nine Iraqi women of childbearing age who suffered from back pain took part in the study; receiving diclofenac (100mg once daily), naproxen (500mg twice daily), etoricoxib (90mg once daily), or a placebo.

Treatment was given for 10 days from day 10 of the onset of their menstrual cycle, with their progesterone levels and follicle diameter analyzed via blood sample and sonography.

“After just ten days of treatment we saw a significant decrease in progesterone, a hormone essential for ovulation, across all treatment groups, as well as functional cysts in one third of patients,” said study investigator Professor Sami Salman, Department of Rheumatology, University of Baghdad.

“These findings show that even short-term use of these popular, over-the-counter drugs could have a significant impact on a woman's ability to have children. This needs to be better communicated to patients with rheumatic diseases, who may take these drugs on a regular basis with little awareness of the impact.”

Of the women receiving NSAIDs, only 6.3% taking diclofenac, 25% taking naproxen, and 27.3% taking etoricoxib ovulated, compared with 100% of the control group that was not taking a pain reliever.

The dominant follicle remained unruptured in 75% of the women taking diclofenac, 25% taking naproxen and 33% of the patients receiving etoricoxib. Rupturing of the dominant follicle and the subsequent release of an oocyte (unfertilized egg), is essential for ovulation to occur.

“These findings highlight the harmful effects NSAIDs may have on fertility, and could open the door for research into a new emergency contraception with a more favorable safety profile than those currently in use,” said Salman.

NSAIDs are among the most common pain relief medicines in the world. Every day more than 30 million Americans use them to relieve pain, lower fever and reduce inflammation.

How Chronic Pain Changes Mood and Motivation

By Pat Anson, Editor

Researchers in California have found the first biological evidence that chronic pain alters regions in the brain that regulate mood and motivation -- raising the risk of depression, anxiety and substance abuse.

In animal studies at UCLA and UC Irvine, researchers found that brain inflammation in rodents that was caused by chronic nerve pain led to accelerated growth and activation of immune cells called microglia. Those cells trigger chemical signals within the brain that restrict the release of dopamine, a neurotransmitter that helps control the brain's reward and pleasure centers.

"For over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction," said Catherine Cahill, associate professor of anesthesiology & perioperative care at UCI, Christopher Evans of UCLA's Brain Research Institute. "Our findings represent a paradigm shift which has broad implications that are not restricted to the problem of pain and may translate to other disorders."

The study also revealed why opioid drugs such as morphine and cocaine may lose their effectiveness as animals transition from acute pain to chronic pain. Cahill and her colleagues learned that opioids fail to stimulate a dopamine response in mice and rats, resulting in impaired reward-motivated behavior.

Treating the rodents with a long-acting antibiotic called minocycline inhibited microglial activation, and restored dopamine release and reward-motivated behavior. That finding suggests that a similar approach could be used in treating chronic pain in humans.

"Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic signaling and reward behavior. These results have broad implications that are not restricted to the problem of pain, but are also relevant to affective disorders associated with disruption of reward circuitry," the study found.

The results of the five-year study appear online in the Journal of Neuroscience.

Cahill and her research team are now trying to establish that pain-derived changes in human brain circuitry can account for mood disorders.

"We have a drug compound that has the potential to normalize reward-like behavior," she said, "and subsequent clinical research could then employ imaging studies to identify how the same disruption in reward circuitry found in rodents occurs in chronic pain patients."

Critics Question Oxygen Therapy for Fibromyalgia

By Pat Anson, Editor

Some experts are challenging the findings of a new clinical study that found that hyperbaric oxygen therapy (HBOT) could be used to treat -- and possibly even cure -- fibromyalgia.

Israeli researchers gave HBOT therapy to dozens of women suffering from fibromyalgia and found there was a significant improvement in their pain and other symptoms. The women were put in pressurized air chambers and breathed pure oxygen for 90 minutes, five times a week for two months.

Researchers say brain scans of the women before and after HBOT proved their theory that additional oxygen alters brain pathology and "repairs" parts of the brain overly sensitized by chronic pain. 

"Brain pathology? This is speculation being presented as established knowledge," said John Quintner, MD, an Australian rheumatologist who maintains that fibromyalgia is not a disease, but a "symptom cluster" that could have many different causes.

tHE INTERIOR OF A HYPERBARIC CHAMBER. COURTESY OF Sagol Center for Hyperbaric Medicine and Research

Fibromyalgia is a poorly understood disorder that is characterized by deep tissue pain, headaches, fatigue, depression and insomnia. The cause is unknown.

"This clinical trial is using a methodology that is predicated upon fibromyalgia being a distinct medical condition," said Quintner, telling Pain News Network that the study proved little, but was "good news for those who manufacture portable HBOT units." 

Researchers at the Sagol Center for Hyperbaric Medicine and Research at the Assaf Harofeh Medical Center and Tel Aviv University were studying the use of HBOT on stroke and concussion patients when they realized that oxygen therapy might also change the neural activity of patients with fibromyalgia.

"Patients who had fibromyalgia in addition to their post-concussion symptoms had complete resolution of the symptoms," said Shai Efrati, MD,  lead author of the study that is published online in PLoS ONE. 

Efrati said some patients will require follow-up sessions of HBOT and some won't need to.

"We have learned, for example, that when fibromyalgia is triggered by traumatic brain injury, we can expect complete resolution without any need for further treatment. However, when the trigger is attributed to other causes, such as fever-related diseases, patients will probably need periodic maintenance therapy."

HBOT puts more oxygen into the bloodstream, which delivers it to the brain. Efrati's earlier studies found that HBOT induces neuroplasticity, which leads to repair of chronically impaired brain functions. Most of the women who participated in the new study had fibromyalgia that the researchers believe was triggered by brain trauma.

DR. SHAI EFRATI

"Symptoms in about 70 percent of the women who took part have to do with the interpretation of pain in their brains," said Eshel Ben-Jacob, a study co-author who is an adjunct professor of biosciences at Rice University. "They're the ones who showed the most improvement with hyperbaric oxygen treatment. We found significant changes in their brain activity.

"Most people have never heard of fibromyalgia. And many who have, including some medical doctors, don't admit that this is a real disorder. I learned from my MD friends that this is not the only case in which disorders that target mainly women raise skepticism in the medical community as to whether they're real or not."

HBOT Claims Called "Crazy" 

One of those skeptics is Fred Wolfe, MD, a prominent fibromyalgia researcher who says the Israeli study lacks proper controls used in most clinical studies -- such as patients being "blinded" to whether they are receiving treatment or a placebo.  

"The fibromyalgia study world is filed with positive studies based on unacceptable controls," said Wolfe. "While I don't know enough about this treatment to be sure, I would tend to think the symptomatic improvement could be based on control and blinding problems. It is possible that the demonstrated effect on the brain of oxygen is separate from the effect of symptoms." 

Wolfe is particularly troubled by a recommendation at the end of the study that fibromyalgia patients should undergo HBOT therapy now, "rather than wait until future studies are completed.”  

"I could only characterize (that) as crazy. Crazy because of the money it would cost and crazy because it posits fibromyalgia as brain disease. FM is not a disease and there is a difference between mechanism and causes. One needs some replication before jumping in," said Wolfe in an email to Pain News Network. 

Many fibromyalgia patients are ready to jump in, based on the comments from readers to our first report about the Israeli study.

"Where do you find studies like this to volunteer? I would so do this," wrote one fibromyalgia sufferer.

"I would so try this. I often feel like I'm not getting enough oxygen," said another.

"Sign me up, please," a woman wrote.

"Is this available in Tucson or Phoenix, Arizona?" asked another woman.

Many fibromyalgia sufferers are desperate for any kind of treatment that would provide relief, much less a cure. In the Israeli study, several patients either drastically reduced or eliminated their use of pain medications.

"The results are of significant importance since, unlike the current treatments offered for fibromyalgia patients, HBOT is not aiming for just symptomatic improvement," said Efrati. "HBOT is aiming for the actual cause -- the brain pathology responsible for the syndrome. It means that brain repair, including even neuronal regeneration, is possible even for chronic, long-lasting pain syndromes, and we can and should aim for that in any future treatment development."

John Quintner is not convinced.

"I have thought long and hard about this issue and have come to the conclusion that we have been dealing with a 'symptom cluster' rather than with a syndrome," he said. "According to my understanding, fibromyalgia is best explained as an  'idiom of human distress' and, as such, is outside the purview of the biomedical model."