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Addiction, Pain, Public Health, Research

Medical marijuana and the risk of painkiller overdose

Medical marijuana and the risk of painkiller overdose

medical marijuanaAfter a study published this fall showed that that opioid overdoses (e.g., with painkillers such as Oxycontin) occur at lower rates in states with legalized medical marijuana, many people interpreted the results as proof that using medical marijuana lowers an individual’s risk of overdose. For example, some speculated that marijuana allows people in pain to forgo using opioids or at least use them in lower doses. Other suggested that medical marijuana reduces users’ consumption of alcohol and anti-anxiety medications, both of which make opioid use more likely to lead to overdose. Still others hypothesized that medical marijuana improves mental health, reducing the risk of intentional opioid overdose (i.e., suicide attempts),

However, all of this speculation was premature. Many things that are associated when geographic areas are compared are not associated in the lives of the individuals who reside in those areas. For example, geographic areas with higher rates of cigarette smoking and higher radon exposure have lower cancer rates, even though individuals who smoke and/or get exposed to radon have higher rather than lower risk of cancer.

The only way to understand the influence of medical marijuana on individuals’ risk of opioid overdose is to actually research individuals, and that is what an Australian team has done. In a recently published study of more than 1,500 people who were on prescribed opioids for pain, they examined experiences with medical marijuana.

Seeking pain relief from medical marijuana was common in the sample, with 1 in 6 participants doing so and 1 in 4 saying they would do so if they had ready access to it. The results did not support the idea that medical marijuana users are at relatively low risk of opioid overdose. Indeed, on every dimension they appeared to be at higher risk than those individuals who did not use medical marijuana for pain.

Specifically, relative to individuals who only used opioids for pain, the medical marijuana users were on higher doses of opioids, were more likely to take opioids in ways not recommended by their doctor, were over twice as likely to have an alcohol use disorder and four times as likely to have a heroin use disorder. Medical marijuana users were also over 50 percent more likely to be taking anti-anxiety medications (benzodiazepines), which when combined with opioids are particularly likely to cause an overdose.

Neither did the medical marijuana users have better mental health. Almost two-thirds were depressed and about 30 percent had an anxiety disorder.   These rates were half again as high as those for non-medical marijuana users.

Medical marijuana thus appears to be commonly sought for pain relief among people who are taking prescribed opioids for pain. But in this population, it’s a marker for much higher rather than lower risk for opioid overdose.

Addiction expert Keith Humphreys, PhD, is a professor of psychiatry and behavioral sciences at Stanford and a career research scientist at the Palo Alto VA. He has served in the past as a senior advisor in the Office of National Drug Control Policy in Washington, DC. He can be followed on Twitter at @KeithNHumphreys.

Previously: Assessing the opioid overdose epidemicTo reduce use, educate teens on the risks of marijuana and prescription drugs and Study shows prescribing higher doses of pain meds may increase risk of overdose
Photo by David Trawin

Health Costs, Pain, Public Health, Research

Study examines trends in headache management among physicians

Study examines trends in headache management among physicians

4175034274_63cd0d4a7c_zAn estimated 12 percent, or 36 million Americans, suffer from migraines, resulting in an economic loss of $31 billion each year due to lost productivity, medical expenses and absenteeism.

Making lifestyle changes, such as exercising regularly, getting adequate sleep, reducing stress and cutting food triggers from your diet, have been shown (.pdf) to be effective ways to manage headache symptoms. But research recently published in the Journal of General Internal Medicine shows that physicians are increasingly ordering medical tests and providing referrals to specialists instead of offering counseling to patients on how changing their behavior could relieve their pain. Medical News Today reports:

The study, which analyzed an estimated 144 million patient visits, found a persistent overuse of low-value, high-cost services such as advanced imaging, as well as prescriptions of opioids and barbiturates. In contrast, the study found clinician counseling declined from 23.5 percent to 18.5 percent between 1999 and 2010.

The use of acetaminophen and non-steroidal anti-inflammatory drugs like ibuprofen for migraine remained stable at approximately 16 percent of the medications. Meanwhile, the use of anti-migraine medications such as triptans and ergot alkaloids rose from 9.8 percent to 15.4 percent. Encouragingly, guideline-recommended preventive therapies – including anti-convulsants, anti-depressants, beta blockers and calcium channel blockers – rose from 8.5 percent to 15.9 percent.

Unlike with the treatment of back pain, researchers found no increase in the use of opioids or barbiturates, whose usage should be discouraged, although they were used in 18 percent of the cases reviewed.

Researchers also found a significant increase in advanced imaging such as CT scans and MRIs, from 6.7 percent of visits in 1999 to 13.9 percent in 2010. The use of imaging appeared to rise more rapidly among patients with acute symptoms, compared to those with chronic headache.

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Pain, Science, Stanford News, Videos

Graduate student explains pain research in two-minute video

Graduate student explains pain research in two-minute video

Earlier this year I wrote about some fascinating research from the lab of chemist Justin Du Bois, PhD, who has been working with naturally occurring toxins with the goal of developing ways of combatting pain. This class of toxins is found in a number of poisonous animals, including the newts scurrying around Stanford campus, puffer fish and mollusks in red tides.

Now, graduate student Rhiannon Thomas-Tran, who has been working with Du Bois, produced a great video describing their approach, complete with some pretty creative drawings.

Previously: Toxins in newts lead to new way of locating pain

Anesthesiology, Pain, Research, Stanford News

Miniature wireless device aids pain studies

Miniature wireless device aids pain studies

DSC_0053Here’s one thing I didn’t know: For every person who goes to the doctor to be treated for chronic pain, less than a half get their pain reduced even by half. I learned that from anesthesiologist David Clark, MD, who recently received a grant from Stanford Bio-X, which supports interdisciplinary teams working on biomedical problems, to improve those odds.

One of Clark’s collaborators is Scott Delp, PhD, who last spring developed a way of using light to activate and deactivate pain neurons in mice. To be clear, the nerves had to be genetically engineered to allow the light to work – not something that can currently be done in humans.

That work pointed to new ways of studying pain, but had a glitch. The light was delivered through fiber optic cables and the mice couldn’t behave normally in their cages. That’s where engineer Ada Poon, PhD, enters the picture. She’s been developing a variety of devices that work wirelessly in the body, and she’s now working on a wireless device to deliver the light to nerves in mice. Here’s what I wrote in an online story yesterday:

Coupling a wireless technology to optogenetics eliminates the wire and allows a mouse to move freely, use an exercise wheel and socialize. Clark said this combination will allow researchers to design experiments that more closely mirror a patient’s experience.

For example, Clark said that when he sees patients they don’t necessarily complain only about the pain. They complain about not wanting to see friends, not being able to go to work, or not being able to do activities they enjoy.

“What we will be able to look at is a more natural measure of pain relief,” Poon said. They could assess whether a treatment allows mice to return to normal activities by tallying time spent on an exercise wheel or socializing.

Clark went on to tell me the value of working in this team: “When you combine people with different skills you will come up with something with truly high impact.”

Previously: Using light to get muscles moving and Stanford researchers demonstrate feasibility of ultra-small, wirelessly powered cardiac device
Image courtesy of Ada Poon

Clinical Trials, Immunology, Pain, Research, Stanford News, Surgery, Technology

Discovery may help predict how many days it will take for individual surgery patients to bounce back

Discovery may help predict how many days it will take for individual surgery patients to bounce back

pandaPost-surgery recovery rates, even from identical procedures, vary widely from patient to patient. Some feel better in a week. Others take a month to get back on their feet. And – until now, anyway – nobody has been able to accurately predict how quickly a given surgical patient will start feeling better. Docs don’t know what to tell the patient, and the patient doesn’t know what to tell loved ones or the boss.

Worldwide, hundreds of millions of surgeries are performed every year. Of those, tens of millions are major ones that trigger massive inflammatory reactions in patients’ bodies. As far as your immune system is concerned, there isn’t any difference between a surgical incision and a saber-tooth tiger attack.

In fact, that inflammatory response is a good thing whether the cut came from a surgical scalpel or a tiger’s tooth, because post-wound inflammation is an early component of the healing process. But when that inflammation hangs on for too long, it impedes rather than speeds healing. Timing is everything.

In a study just published in Science Translational Medicine, Stanford researchers under the direction of perioperative specialist Martin Angst, MD, and immunology techno-wizard Garry Nolan, PhD, have identified an “immune signature” common to all 32 patients they monitored before and after those patients had hip-replacement surgery. This may permit reasonable predictions of individual patients’ recovery rates.

In my news release on this study, I wrote:

The Stanford team observed what Angst called “a very well-orchestrated, cell-type- and time-specific pattern of immune response to surgery.” The pattern consisted of a sequence of coordinated rises and falls in numbers of diverse immune-cell types, along with various changes in activity within each cell type.

While this post-surgical signature showed up in every single patient, the magnitude of the various increases and decreases in cell numbers and activity varied from one patient to the next. One particular factor – changes, at one hour versus 24 hours post-surgery, in the activation states of key interacting proteins inside a small set of “first-responder” immune cells – accounted for 40-60 percent of the variation in the timing of these patients’ recovery.

That robust correlation dwarfs those observed in earlier studies of the immune-system/recovery connection – probably because such previous studies have tended to look at, for example, levels of one or another substance or cell type in a blood sample. The new method lets scientists simultaneously score dozens of identifying surface features and goings-on inside cells, one cell at a time.

The Stanford group is now hoping to identify a pre-operation immune signature that predicts the rate of recovery, according to Brice Gaudilierre, MD, PhD, the study’s lead author. That would let physicians and patients know who’d benefit from boosting their immune strength beforehand (there do appear to be some ways to do that), or from pre-surgery interventions such as physical therapy.

This discovery isn’t going to remain relevant only to planned operations. A better understanding, at the cellular and molecular level, of how immune response drives recovery from wounds may also help emergency clinicians tweak a victim’s immune system after an accident or a saber-tooth tiger attack.

Previously: Targeting stimulation of specific brain cells boosts stroke recovery in mice, A closer look at Stanford study on women and pain and New device identifies immune cells at an unprecedented level of detail, inside and out
Photo by yoppy

Behavioral Science, Pain, Podcasts

Chronic pain: Getting your head around it

Chronic pain: Getting your head around it

Less Pain cover - smallerI have to admit: When it comes to pain, I’m a total wimp. The few times I’ve approached anything near chronic pain was in my neck – the result from unilateral breathing as a lap swimmer. When I had the pain, I was obsessed with it, and it was a complete drag on my psyche. My painful experience gave me deep empathy for anyone who lives with chronic pain.

Beth Darnall, PhD, is a clinical associate professor at the medical school and a clinical psychologist at Stanford’s Pain Management Center. She has practiced this unique specialty – pain psychology – for the past 10 years, working with chronic pain sufferers to find alternative means to controlling their pain rather than being stuck in a downward spiral of opioid use. And she’s written a new book, Less Pain, Fewer Pills, where she details a methodical approach that enables one to get their “head” out from their pain.

Clearly it’s not all attitude, but a significant portion of pain is how we think about it and catastrophize it and therefore unknowingly give it strength. She told me in this 1:2:1 podcast that “early life trauma can lead to changes in the central nervous system and immune systems… that could prime someone to experience chronic pain later on.” She also said:

We have just pure genetics, an underlying predisposition to acquire chronic pain… But we also know that a person’s psychological makeup, what the person brings to the table, is a big predictor in terms of whether or not their pain resolves or whether it becomes entrenched.

I asked Darnall whether her role as a clinical psychologist helps patients rethink their pain. She told me, “A key message that I bring forward to the table is that pain isn’t something that just happens to us. Once we acquire chronic pain we are constantly participating with our pain in terms of our thoughts, our beliefs, our emotions, and our choices. If we can focus on that and optimize our control there, then we can set ourselves up to have the best response to all of the treatments that our doctors are going to be trying for us.”

If you suffer from chronic pain or know someone who does, I hope you’ll find this conversation with Darnall of value.

Previously: Stanford researchers address the complexities of chronic pain, Exploring the mystery of pain, Relieving Pain in America: A new report from the Institute of Medicine, Stanford’s Sean Mackey discusses recent advances in pain research and treatment and Oh what a pain

Addiction, In the News, Pain, Public Health

Stanford addiction expert: It’s often a "subtle journey" from prescription-drug use to abuse

Stanford addiction expert: It's often a "subtle journey" from prescription-drug use to abuse

Here are some frightening facts you might not know: Drug overdose death rates in the United States have more than tripled since 1990, with the majority of drug-related deaths caused by prescription drugs. And as of 2010, about 18 women in the U.S. die every day of a prescription painkiller overdose. Prescription-drug abuse, which we’ve written about extensively here on Scope, is a very real and pressing issue – and it was the focus of a recent Forum on KQED-FM.

Among the panelists on Friday’s show was Stanford addiction psychiatrist Anna Lembke, MD, who made the important point that most people who end up addicted to prescription painkillers didn’t start out “looking for a buzz” and that most doctors who prescribe the drugs are merely trying to help their patients. As she explained to listeners:

The problem with… prescription opioids is that they actually do work for pain initially… But for most people, after you take them every day for let’s say a month or more, [you] build up tolerance where they stop working so then you need more of the same drug to get the same effect and it escalates on like that. I really think the process is insidious, both for the patients who become addicted and the doctors who prescribe them. It happens in a subtle journey – when all of the sudden [patients are] using them not just for pain but also maybe to relax themselves, to lift their mood, to be able to go out to a party if they’re feeling anxious, and the doctors continue to prescribe them because they started out working, the patients were happy [and] their function improved. The dose is escalating, but they want to keep the patient happy for all kinds of reasons.

The entire conversation is worth a listen.

Previously: Why doctors prescribe opioids to patients they know are abusing them, Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers, Report shows over 60 percent of Americans don’t follow doctors’ orders in taking prescription meds and Study shows prescribing higher doses of pain meds may increase risk of overdose and Prescription drug addiction: How the epidemic is shaking up the policy world

Pain, Research, Stanford News

New painkiller could tackle pain, without risk of addiction

New painkiller could tackle pain, without risk of addiction

painkillersThose suffering from chronic pain, take note: A new pain-reliever may soon be on the scene that lacks the “high” of opioids and the cardiac-risk of non-steroidal anti-inflammatory (NSAIDs) drugs such as aspirin. The compound reduced inflammatory pain in mice, according to research by a team of Stanford scientists led by Daria Mochly-Rosen, PhD, a professor of chemical and systems biology.

Mochly-Rosen discovered the compound, called Alda-1, more than five years ago while searching for the reason moderate alcohol use can decrease the severity of heart attacks. She found an enzyme, called aldehyde dehydrogenase 2, that breaks down a family of alcohol byproducts, called aldehydes. Aldehydes also cause pain in mice and Alda-1 relieves the pain, Mochly-Rosen said.

“I’m not a pain expert,” Mochly-Rosen says in our release on the Science Translational Medicine paper. “We hit this enzyme for a completely different reason. Hopefully this will help people who have pain.”

Alda-1 — coincidentally, Alda is also the name of Mochly-Rosen’s 87-year-old mother — works by knocking aldehyde dehydrogenase 2 into high gear. Say goodbye to the aldehydes, and goodbye to the pain.

Mochly-Rosen’s discovery of the link between pain and Alda-1 is a big deal for many reasons, including the suffering of thousands addicted to opioids such as Oxycontin. It’s also particularly meaningful for the millions in the Han Chinese ethnic group who suffer from alcohol flush.  They have a mutation in aldehyde hydrogenate 2, which makes it uncomfortable to drink alcohol and causes sufferers to turn red.

The inflammation is caused by the build-up of aldehydes, which are byproducts of alcohol. Alcohol-flush syndrome, as it’s sometimes called, has been recognized for decades.

The researchers created a mouse with a mutation akin to the enzyme mutation in humans. When they injected aldehydes into the mice, the mice with the mutation felt more pain than the other mice. And Alda-1 also relieved their pain.

Dribbles of evidence suggest some Asians are more sensitive to pain. Now, Mochly-Rosen and her team plan to investigate if the susceptibility stems from the enzyme mutation.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Another big step toward building a better aspirin tablet, Blocking addiction risks of morphine without reducing its pain-killing effects, Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers, and Stanford’s Sean Mackey discusses recent advances in pain research and treatment
Photo by Michelle Tribe/Wikimedia Commons

Genetics, Medicine and Society, Pain, Research, Science, Stanford News

From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies

From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies

Basic RGBStanford bioengineer Christina Smolke, PhD, and her team have been on a decade-long mission to replicate how nature produces opium in poppies by genetically engineering the DNA of yeast and then further refining the process to manufacture modern day opioid drugs such as morphine, codeine and the well-known painkiller Vicodin.

Smolke outlined the methods in a report  (subscription required) published in this week’s edition of Nature Chemical Biology, which details the latest stages in the process of manufacturing opium-based medicines, from start to finish, in fermentation vats, similar to the process for brewing beer.

An article published today in the Stanford Report offers more details:

It takes about 17 separate chemical steps to make the opioid compounds used in pills. Some of these steps occur naturally in poppies and the remaining via synthetic chemical processes in factories. Smolke’s team wanted all the steps to happen inside yeast cells within a single vat, including using yeast to carry out chemical processes that poppies never evolved to perform – such as refining opiates like thebaine into more valuable semi-synthetic opioids like oxycodone.

So Smolke programmed her bioengineered yeast to perform these final industrial steps as well. To do this she endowed the yeast with genes from a bacterium that feeds on dead poppy stalks. Since she wanted to produce several different opioids, her team hacked the yeast genome in slightly different ways to produce each of the slightly different opioid formulations, such as oxycodone or hydrocodone.

“We are now very close to replicating the entire opioid production process in a way that eliminates the need to grow poppies, allowing us to reliably manufacture essential medicines while mitigating the potential for diversion to illegal use,” Smolke added.

While it could take several more years to refine these last steps in the lab, bioengineering opioids would eventually lead to less dependence on legal poppy farming, which has numerous restrictions and international dependencies from other countries. It would also provide a reliable supply and secure process for manufacturing important pain killing drugs.

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

Previously: Blocking addiction risks of morphine without reducing its pain-killing effects, Do opium and opioids increase mortality risk? and Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers 
Photo by Kate Thodey and Stephanie Galanie

Behavioral Science, Chronic Disease, Neuroscience, Pain, Research, Stanford News

Obscure brain chemical indicted in chronic-pain-induced "Why bother?" syndrome

Obscure brain chemical indicted in chronic-pain-induced "Why bother?" syndrome

why botherChronic pain, meaning pain that persists for months and months or even longer (sometimes continuing well past the time when the pain-causing injury has healed), is among the most abundant of all medical afflictions in the developed world. Estimates of the number of people with this condition in the United States alone range from 70 million to 116 million adults – in other words, as much as half the country’s adult population!

No picnic in and of itself, chronic pain piles insult on injury. It differs from a short-term episode of pain not only in its duration, but also in triggering in sufferers a kind of psychic exhaustion best described by the rhetorical question, “Why bother?”

In a new study in Science, a team led by Stanford neuroscientist Rob Malenka, MD, PhD, has identified a particular nerve-cell circuit in the brain that may explain this loss of motivation that chronic pain all too often induces. Using lab mice as test subjects, they showed that mice enduring unremitting pain lost their willingness to perform work in pursuit of normally desirable goals, just as people in chronic pain frequently do.

It wasn’t that these animals weren’t perfectly capable of carrying out the tasks they’d been trained to do, the researchers showed. Nor was it that they lost their taste for the food pellets which with they were rewarded for successful performance – if you just gave them the food, they ate every bit as much as normal mice did. But they just weren’t willing to work very hard to get it. Their murine morale was shot.

Chalk it up to the action of a mysterious substance used in the brain for god-knows-what. In our release describing the study, I explained:

Galanin is a short signaling-protein snippet secreted by certain cells in various places in the brain. While its presence in the brain has been known for a good 60 years or so, galanin’s role is not well-defined and probably differs widely in different brain structures. There have been hints, though, that galanin activity might play a role in pain. For example, it’s been previously shown in animal models that galanin levels in the brain increase with the persistence of pain.

In a surprising and promising development, the team also found that when they blocked galanin’s action in a particular brain circuit, the mice, while still in as much pain as before, were once again willing to work hard for their supper.

Surprising, because galanin is a mighty obscure brain chemical, and because its role in destroying motivation turns out to be so intimate and specific. Promising, because the discovery suggests that a drug that can inhibit galanin’s activity in just the implicated brain circuit, without messing up whatever this mystery molecule’s more upbeat functions in the brain might be, could someday succeed in bringing back that drive to accomplish things that people in chronic pain all too often lose.

Previously: “Love hormone” may mediate wider range of relationships than previously thought, Revealed: the brain’s molecular mechanism behind why we get the blues, Better than the real thing: How drugs hot-wire our brain’s reward circuitry and Stanford researchers address the complexity of chronic pain
Photo by Doug Waldron

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