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PAIN MANAGEMENT STUDY REVEALS PATIENT CONFUSION ABOUT OPIOID ADDICTION

Emergency department patients have misperceptions about opioid dependence and want more information about their pain management options, according to a new study from researchers at the Perelman School of Medicine at the University of Pennsylvania (Penn). The study, published online in the Annals of Emergency Medicine on April 9, 2015, found that patients seen in the emergency department for acute pain expressed a desire for better communication from physicians about their pain management options, along with discussion of the risks of opioid dependence. The study used semistructured open-ended telephone interviews with 23 patients (mostly women, ages 18–65) discharged from the Hospital of the University of Pennsylvania after being seen in the emergency department during a 4-month period in 2014, for pain related to broken bones in the arms or legs, kidney stones, or musculoskeletal back injury. Although the patients discussed a variety of topics related to their experiences with communication around pain, the main themes of the interviews included opioid dependence and addiction, and patient-provider communication about pain management. The themes patients revealed around opioid dependence included

1. Fear of developing dependence or addition,

2. Worries about following prescribed dosing preventing the possibility of addiction,

3. Relying on media and other individuals as a source of information about opioids, and

4. Awareness of physicians’ need to balance patients’ pain management needs and safe opioid prescribing guidelines.

“It was interesting to find that patients believe that taking an opioid as prescribed prevents the possibility of addiction, but also that patients are learning about opioids from television and from friends and acquaintances—not healthcare providers,” said senior author Zachary F. Meisel, MD, MPH, MS, assistant professor and attending physician in the Department of Emergency Medicine, who oversaw the study led by Robert J. Smith, BS, a medical student at Penn. “There's clearly a significant need for emergency departments to improve education around the risks of opioid misuse.”

There were also several themes that emerged around patient-provider communication about pain management. Patients often reported that they desired engagement in decisions about the treatment plan, better communication about the cause of their pain, consideration of how the pain is affecting their life, and more empathy from providers, and they also felt that fragmentation in communication between providers was detrimental to their treatment.

“Patients realize that emergency departments are busy places, but that doesn't reduce their desire to have meaningful interactions with their care providers,” said Meisel. “Patients want to be given information in a straight-forward way and then listened to, so that they leave feeling like they know what was causing their pain, what their pain management options were, and that their treatment preferences were heard.”

The researchers are now using the data from this study to develop short video narratives of patient stories related to pain in the emergency department, which will then be tested as an intervention to improve patient understanding of their pain management options and the risks associated with opioid misuse.

The other Penn co-authors include Karin Rhodes, MD, MS, Breah Paciotti, MPH, Sheila Kelly, MPH, and Jeanmarie Perrone, MD. Funding was provided by a grant from the Agency for Healthcare Quality and Research (R18HS021956).

DRUG RESEARCH AND DEVELOPMENT COSTS: $1.7 BILLION AND RISING

The significant costs of developing new, life-saving drugs and treatments has reached over $1.7 billion per drug over a span of 10–12 years according to a report entitled “The High Costs of Inventing New Drugs—And of Not Inventing Them.” The report is accessible online at: http://www.ipi. org/ipi_issues/detail/the-high-cost-of-inventing-new-drugs-and-of-not-inventing-them-2. The report was released on April 17, 2015. The mounting costs can be attributed not only to the growing complexity of drugs, but also due to bureaucratic red tape and the short length of a drug's patent life, two issues that can be mitigated by legislative reforms.

“While drug companies are proceeding with research to create new and innovative drugs, drug development remains very expensive, and likely to grow even more so,” says the author of the report, Institute for Policy Innovation (IPI) resident scholar Merrill Matthews, PhD. The institute is an independent, nonprofit public policy organization. Matthews says in addition to the cumbersome Food and Drug Administration (FDA) approval process that lacks incentives to expediently get drugs to market, manufacturers are increasingly developing far more complex biologic drugs, treatments, and even cures, as opposed to simpler pill therapies of the past. And although price controls are critics’ primary solution to the high cost of drugs, price controls would simply halt the R&D (research and development) process altogether.

Matthews explains that economist Joe DiMasi of the Tufts Center for the Study of Drug Development recently pegged the total out-of-pocket cost to develop and approve a new drug at about $1.707 billion, a figure that nearly matches his own “back of the envelope” approach of $1.756 billion, found by simply dividing the drug manufacturers’ reported R&D by the number of newly approved drugs. “Whichever method is used, it's clear that drug development is very expensive,” writes Matthews.

“There are ways to make new drugs less expensive, i.e., cut down on some of the bureaucratic oversight or lengthening the patent life, which means the manufacturers would have more time to recoup their investment, but both efforts would require a major legislative push,” said Matthews.

“Drug manufacturers plowed millions of dollars into finding a treatment for AIDS once it became clear the disease would take thousands of lives. The research and development was costly and didn't emerge overnight, but being diagnosed with AIDS is no longer a death sentence,” said Matthews. “If the cost of creating new drugs is high, the cost of not having any new drugs is immeasurable.”

CONSUMER PAIN ADVOCACY TASK FORCE RESPONSE TO PROPOSED NATIONAL PAIN STRATEGY

The Consumer Pain Advocacy Task Force (CPATF) was formed in 2014 as a coalition of 17 consumer organizations working to improve the well-being of those living with pain. Members include American Cancer Society Cancer Action Network; American Chronic Pain Association; C-Change; Chronic Pain Research Alliance; Global Health Living Foundation; Interstitial Cystitis Association; National Fibromyalgia & Chronic Pain Association; National Patient Advocate Foundation; Pain Connection; PAINS; Power of Pain Foundation; Reflex Sympathetic Dystrophy Syndrome Association; State Pain Policy Advocacy Network; The Foundation for Peripheral Neuropathy; The Pain Community; The TMJ Association; and US Pain Foundation. In April 2015, the CPATF released the following in response to the National Pain Policy draft.

To address the urgent public health crisis of chronic pain in America, the Department of Health and Human Services (HHS) released a draft of the newly developed National Pain Strategy (NPS) and is soliciting comments from the public. The Consumer Pain Advocacy Task Force (CPATF) is a new coalition of seventeen consumer organizations and advocacy groups created specifically to promote, support and monitor the implementation of the NPS. The Task Force is calling for HHS to proactively develop a federal oversight body and start the budgeting process now, so that HHS can swiftly commence implementation of the plan as soon as it is approved and released.

The National Pain Strategy is the first-ever, comprehensive, population-level strategic plan to advance pain research, education, care and prevention, and was developed in response to the imminent need to transform how pain is perceived, assessed and treatment in America. The NPS process began after the seminal 2011 Institute of Medicine (IOM) report, Relieving Pain in America, determined that over 100 million American adults live with life-altering chronic pain, at an annual economic cost burden of $600 billion. This equals a national epidemic with costs far exceeding that of any other disease state or disorder in the U.S.

“Developed by six federal health agencies and 80 well-respected experts from the medical-scientific, public, private, federal, patient and advocacy communities, the NPS represents hope for the millions of Americans and their loved ones affected by devastating chronic pain,” states Amy Goldstein, MSW, one of the 17 members of the Consumer Pain Advocacy Task Force. “Now, we must ensure that adequate funding is allocated for this effort and that the NPS is implemented in a coordinated and efficient manner to enact long-overdue change in the lives of people who are suffering gravely. The CPATF applauds HHS for its leadership on this issue, and stands ready to do its part to support the Department and federal agencies in the implementation process.”

The CPATF is encouraging a robust and diverse community response during the NPS public comment period, and is asking other consumer groups to join its efforts to promote the plan's implementation, as well as raise general awareness of the challenges impacting those with chronic pain. The CPATF unites around the following beliefs, which guide the group's collective work:

• Chronic pain is a real and complex disease that may exist by itself or along with another medical condition

• Chronic pain is an unrecognized and under-resourced public health crisis with devastating personal and economic impact

• Effective pain care requires access to a wide range of treatment options

• Allowing people to suffer with unmanaged pain is immoral and unethical

A3 ADENOSINE RECEPTOR CAN ACTIVATE “OFF SIGNALS” FOR PAIN

In a study published in the April issue of the Journal of Neuroscience, Saint Louis University scientists led by professor of pharmacological and physiological sciences Daniela Salvemini, PhD, discovered that drugs targeting the A3 adenosine receptor can “turn off” pain signals in the spinal cord to provide relief from chronic pain. Salvemini and colleagues teamed up with researchers from the National Institutes of Health, the University of Arizona, and two institutes in Quebec, Canada, to investigate a new target for treating chronic pain: the A3 adenosine receptor or A3AR.

In earlier studies, Salvemini's laboratory demonstrated that two drugs that target the A3AR—IB-MECA and MRS5698—were effective in treating several models of chronic pain, including painful chemotherapy-induced neuropathy, metastatic cancer pain, and nerve injury. More recently, the group sought to uncover the mechanism of A3AR pain relief.

“Chronic pain can result from the loss of regulatory mechanisms in the nervous system pathway that transmits pain,” Salvemini said. “Adenosine acts as a regulatory signaling molecule in other areas of the nervous system, so we hypothesized that A3AR might also play a role in regulating pain signals during pain processing.”

Salvemini and colleagues found that A3AR drugs not only relieved pain, but did so by activating an inhibitory transmitter system known as the γ-aminobutyric acid (GABA) system. In areas of the spinal cord and brain dedicated to pain processing, A3AR activation promoted GABA signaling by preventing the breakdown and removal of GABA from neuronal synapses.

“In chronic pain, GABA signaling is often lost or diminished. Our A3AR drugs were able to restore GABA signaling in areas that process pain and ‘turn off’ the signals that maintain the pain state,” Salvemini said.

With A3AR drugs demonstrating good safety profiles in clinical trials as anti-inflammatory and anticancer agents, Salvemini and colleagues are enthusiastic about the potential of these new drugs to treat chronic pain in patients.

“Several lead molecules for prospective clinical use have been identified through our collaboration with Dr. Kenneth Jacobson at the National Institutes of Health and we are very excited about the potential for translational therapeutic impact,” Salvemini said.

Their laboraotry will continue to investigate the intricate mechanisms underlying A3AR pain relief with the hope of providing better palliative care to individuals suffering from unnecessary chronic pain. This research was funded by grants from the National Cancer Institute (R01CA169519), with additional support from the Saint Louis Cancer Center, the Canadian Institutes of Health Research, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Intramural Research Program.

PATHWAYS TO SAFER OPIOID USE

Pathways to Safer Opioid Use is an immersive, interactive training tool that was designed using the opioid-related recommendations outlined in the National Action Plan for Adverse Drug Event Prevention (ADE Action Plan). The Plan can be accessed at: http://health.gov/hcq/ade.asp#action-plan.

The training uses the principles of health literacy and a multimodal, team-based approach to promote the appropriate, safe, and effective use of opioids to manage chronic pain.

This Web-based training allows you to assume the role of four playable characters who make dec- isions—controlled by you—about preventing opioid-related adverse drug events (ADEs). The characters represent the following roles: primary care physician, nurse, pharmacist, and patient.

In this behavior-based training using interactive video, you will learn how to

• Apply health literacy strategies to help patients understand and act on information to prevent opioid-related ADEs

• Identify individual risk factors, opioid medications, and interactions that place individuals with chronic pain at increased risk for opioid-related ADEs

• Recognize the importance of a multidisciplinary, team-based approach to treating patients with chronic pain

• Demonstrate the ability to combine the principles of the Health Literate Care Model and the biopsychosocial model of chronic pain management through case study examples.

The online program can be accessed at: http:// health.gov/hcq/training.asp#pathways.

EARLY USE OF PALLIATIVE CARE IN CANCER IMPROVES PATIENTS’ LIVES, OUTCOMES FOR CAREGIVERS

A randomized clinical trial conducted by Dartmouth investigators Kathleen Lyons, ScD, Tor Tosteson, ScD, Zhigang Li, PhD, and collaborators noted significant improvement in several measures among those who began palliative care early. Their findings are described in “Early Versus Delayed Initiation of Concurrent Palliative Care Oncology: Patient Outcomes in the ENABLE III Randomized Controlled Trial,” published in the April 20 issue of the Journal of Clinical Oncology.

“Survivorship and quality of life are of great interest in clinical cancer research, but can be difficult to evaluate because of high mortality and the need to measure patient-reported outcomes,” explained Tosteson, a biostatistician at Dartmouth's Norris Cotton Cancer Center (NCCC). “We developed trial designs and analytic methods that allow the joint estimation and comparison of survival and quality of life data between different treatment strategies. The ENABLE trials have helped to establish the beneficial effects of palliative care on overall survival by interventions targeting patient outcomes.”

The team's previous ENABLE II trial established that a carefully designed intervention for patients with late stage cancers improved both quality of life and survival. The recently published ENABLE III study found that an earlier intervention strategy improved survival further.

In this study, investigators researched the outcomes of palliative care that began at the first visit or 3 months later among 207 patients with late stage cancer. Although the early-entry participants’ patient-reported outcomes were not statistically different from the late-entry participants, their 1-year survival after enrollment was improved compared with those who entered later. Additionally, outcomes for caregivers were improved.

“Early interventions for caregivers lowered their depression and stress burden in the last month of the patient's life,” reported Lyons.

“Early Versus Delayed Initiation of Concurrent Palliative Care Oncology: Patient Outcomes in the ENABLE III Randomized Controlled Trial,” was supported by grants R01NR011871 and R03NR014915 from the National Institute for Nursing Research, P30CA023108 from the National Cancer Institute, and UL1 TR001086 from the National Center for Advancing Translational Sciences; by Norris Cotton Cancer Center pilot funding; and by Mentored Research Scholar Grant MRSG 12-113-01-CPPB in Applied and Clinical Research from the American Cancer Society.

ROLE OF DOPAMINE IN CHRONIC PAIN

Researchers from the University of Texas (UT) at Dallas and others traced the path of pain signals between the brain and spinal cord in mice and found removing a group of dopamine-containing cells selectively reduced chronic pain. Senior author Ted Price, associate professor in behavioral and brain sciences at UT Dallas, says the study reveals a new role for dopamine in helping maintain chronic pain states, and suggests that this may open up new opportunities to target medicines that could reverse chronic pain.

In acute pain, signals travel from the site of the injury to the spinal cord, which passes them on in the form of other chemical or electrical pulses that in turn are relayed to brain cells that distribute them throughout the brain. In people with chronic pain, their nerve cells continue to send pain signals to the brain—even in the absence of injury—but the causes of this are not known. The brain has several pain centers, and evidence suggests chronic pain alters how they are activated. Targeting A11 dopamine-containing cells permanently reversed chronic pain in mice.

The new study shows that a group of dopamine-containing cells called A11 do not affect acute pain, but they appear to have a profound effect on chronic pain. In their paper, Professor Price and colleagues describe how they permanently reversed a chronic pain state in mice by targeting A11 cells. They got the idea for the study because they noticed other studies on chronic pain had looked at the role of other brain chemicals such as norepinephrine and serotonin. So they decided to take a look at dopamine. The researchers concluded that their study increases our understanding of the causes of chronic pain and the factors that contribute to it, which should eventually lead to more effective treatments.

POST-CONCUSSION SYNDROME

Investigators at McMaster University in Hamilton, Ontario, Canada, have developed a new understanding of post-concussion syndrome, answering questions that have been plaguing researchers in the field. Their study, published in the medical journal Brain, Behavior, and Immunity, provides an explanation for why many people with even very trivial head injuries, or even injuries to other parts of their bodies, experience incapacitating post-concussion-like syndromes. These symptoms include headaches, dizziness, cognitive impairment, and other neuropsychiatric symptoms such as irritability, anxiety, and insomnia.

“It's inflammation that they have in common,” said Michel Rathbone, a professor of medicine for McMaster's Michael G. DeGroote School of Medicine and a lead author of the paper. “Rather than a concussion, we'd like to propose a unifying umbrella term of post-inflammatory brain syndromes or PIBS.”

He added that the research will encourage scientists to open up new lines of research into understanding the cause of post-concussion symptoms in the absence of obviously visible brain injury on conventional imaging and into the treatment of these symptoms by targeting inflammatory mediators. For example, people who have a very subtle genetic change in a certain inflammatory protein have poorer recovery after brain injury.

It also explains why many social factors appear to play a role in development of symptoms: “We know that the immune system can be modulated, or sensitized by the current and even the previous environment an individual was in. These social factors, such as preexisting stressors, depression or anxiety, may actually be, in a way, biological factors.”

Rathbone added that this will provide hope for individuals with cognitive dysfunction after major infections, surgeries, and traumas, as it suggests that current and future treatments for concussion may hold a benefit for these individuals.

“This research opens many doors for so many different patients. We are excited to be starting a totally new approach to the field, and we look forward to making a difference for the patients of the future.”

PHARMACOKINETIC DATA RELEASED ON THIRD-GENERATION ZOHYDRO

On May 5, 2015, Pernix Therapeutics Holdings, Inc., a specialty pharmaceutical company, announced the successful completion of a human pharmacokinetic equivalence study with ZX007, an innovative abuse-deterrent tablet formulation of hydrocodone bitartrate. The clinical study evaluated the pharmacokinetics and safety of prototype formulations developed by Altus Formulation using its proprietary INTELLITAB™ technology, for comparison with Zohydro® ER, resulting in the selection of the final ZX007 prototype for pivotal clinical studies. Damon Smith, CEO of Altus Formulation said, “We are very happy that ZX007 is performing in the way we expected in human studies and we look forward to working with the Pernix team to complete development.”

Study results demonstrated that the selected ZX007 formulation is pharmacokinetically equivalent with currently marketed Zohydro ER with BeadTek and that it has a consistent safety profile. Selection of the formulation enables the start of pivotal clinical studies later this year, paving the way for the NDA (new drug application) submission for ZX007 in mid-2016. Doug Drysdale, President, Chairman, and CEO of Pernix said, “We are pleased to have identified the right formulation to move forward into clinical trials, to bring the clinical benefits of ZX007 to patients suffering with chronic pain. Pernix remains committed to supporting the appropriate use of opioids, which includes following best practices for physicians and their patients living with chronic pain, as well as making abuse-deterrent products available.”

The Zohydro ER NDA and related investigational new drug applications were transferred from Zogenix to Pernix immediately upon closing on April 24, 2015, and Pernix has assumed regulatory and financial responsibility for the ongoing efforts related the development of ZX007, with Zogenix providing assistance in the clinical development of the program under a Transitional Services Agreement for up to 18 months.

DISCOVERY MAY FACILITATE NEW ADVANCES IN NON-NARCOTIC MANAGEMENT OF PAIN

Research published online April 30 in the journal Neuron by neuroscientists at Washington University School of Medicine in St. Louis reports that they have found a way to activate opioid receptors with light. The scientists melded the light-sensing protein rhodopsin to key parts of opioid receptors to activate receptor pathways using light. They were also able to affect the behavior of mice by injecting the receptors into the brain, using light instead of drugs to stimulate a reward response. With further investigation, the team hopes to develop ways to use light to relieve pain, a line of discovery that also could lead to better pain-killing drugs with fewer side effects.

As a precursor to that achievement, the researchers are attempting to learn the most effective ways to activate and deactivate the opioid receptor's pathways in brain cells. Michael Bruchas, PhD, the study's principal investigator, explained that working with light rather than drugs makes it much easier to understand how the receptors function within the complex array of cells and circuits in the brain and spinal cord. This understanding has been complicated by the fact that opioid receptors have multiple functions in the body. In this research, by combining the rhodopsin protein, which senses light in the eye's retina, with a mu-opioid receptor, the team were able to build a receptor that responds to light in exactly the same way that standard opioid receptors respond to opioid analgesics.

SUBSTANCE ABUSE RISK NO GREATER IN PEOPLE USING MEDICAL MARIJUANA WITH PRESCRIBED OPIOIDS

Among people who use medical cannabis for chronic pain, those who also take prescription pain medications are not at increased risk for serious alcohol and other drug involvement, according to a study in the May issue of the Journal of Studies on Alcohol and Drugs (Perron BE, Bohnert K, Perone AK, Bonn-Miller MO, Ilgen M. Use of prescription pain medications among medical cannabis patients: comparisons of pain levels, functioning, and patterns of alcohol and other drug use. Journal of Studies on Alcohol and Drugs. 2015;76:406–413).

Although medical cannabis is being used increasingly often as an alternative to opioids for chronic pain, in many patients it is being used in conjunction with opioids. This use has raised concerns that the combination could increase the risk of patients using substances such as alcohol and other drugs as well. In this study, researchers looked at data from 273 patients at a medical cannabis clinic in Michigan. More than 60% of the participants reported also using prescription pain medication within the past month. There were no significant differences in the rate of co-occurring substance use between those who used prescription pain medication and those who did not.

This intersection of medical cannabis and prescription pain medication has not been widely studied, but the results still surprised the researchers, says lead study author Brian Perron, PhD, of the School of Social Work at the University of Michigan.

“We expected that persons receiving both cannabis and prescription opioids would have greater levels of involvement with alcohol and other drugs,” Perron said. “However, that wasn't the case—although persons who were receiving both medical cannabis and prescription opioids reported higher levels of pain, they showed very few differences in their use of alcohol and other drugs compared to those receiving medical cannabis only.”

Overall, subjects in the study reported higher rates of alcohol and other (noncannabis) drug use, both in their lifetime and in the past 3 months, than in the general population. But use of other drugs—including alcohol, cocaine, sedatives, street opioids, and amphetamines—did not differ between medical cannabis users who took prescription pain medications and those who did not.

Because prescription pain medications carry a more serious risk of addiction or overdose, medical cannabis may be a safer alternative in pain management, assuming that cannabis has efficacy for longer-term analgesia and is used as intended, according to Perron. But communication between doctor and patient is key.

“We actually know very little about who is receiving both medical cannabis and prescription pain medications,” said Perron. “Physicians do not actually ‘prescribe’ medical cannabis—they only certify whether the patient has a qualifying condition, which allows the patient to gain access to medical cannabis. The system of dispensing medical cannabis is completely separate from prescription medications, so physicians may not know whether a given patient is using medical cannabis, how much, and in what form.”

Perron points out that this was an observational study, so inferences must be made carefully. But he does conclude that it is important that health care providers become knowledgeable about medical cannabis laws and can have open conversations with their patients, especially as more states give access to cannabis for medical and recreational purposes.

MASSACHUSETTS TO EDUCATE PRESCRIBERS AND PATIENTS ABOUT PRESCRIPTION DRUG ABUSE

Saying that “There is no more important public health issue today than the opioid epidemic,” the president of the Massachusetts Medical Society today announced on May 15 that the organization is launching a comprehensive campaign to educate physicians and patients about safe prescribing and the storage and disposal of prescription pain medications.

“Physicians must step forward immediately,” said Dennis M. Dimitri, MD, president of the statewide association of physicians with nearly 25,000 members, “to do everything we can to help bring this devastating problem under control.” Citing statistics from the Centers for Disease Control and Prevention, Dr. Dimitri noted that more than 80% of people who misuse prescription pain medications are using drugs prescribed to someone else. He also called attention to a recent poll by the Harvard School of Public Health that discovered that nearly 4 in 10 Massachusetts residents personally know someone who has abused prescription pain medications.

Dr. Dimitri said that although he believes most physicians prescribe responsibly, the data “tells me that there are too many doses of opioid medications in circulation. By limiting this supply and ensuring that opioids are available only to patients who truly need them, we can make a big impact on the Commonwealth's opioid crisis.”

Dimitri said the Medical Society's campaign will have three components:

1. Guidelines for prescribers to help them make the right decisions for their patients

2. Free educational resources for prescribers to help inform their judgments

3. Information on the critical aspects of storage and disposal of prescription drugs for patients and families

The guidelines for prescribers are being recommended for use by all physicians, Dr. Dimitri said, and are not designed to micromanage care, but to improve patient care and lessen the risks associated with opioid prescribing. “We recognize that each patient is different, “he said, “and in all cases, a prescriber's sound clinical judgment is important. However, we also believe that several principles should govern the exercise of this clinical judgment.”

The second component of the effort focuses on education as a key element in reducing prescription drug abuse. Dr. Dimitri said the Medical Society will make its pain management courses available free to all prescribers until further notice. “We intend to remove as many barriers to prescriber education as possible,” said Dr. Dimitri. The final element of the campaign is a collaborative effort with the Partnership for Drug Free Kids and its Medicine Abuse Project to disseminate information about safe storage and proper disposal of opioid medications—key elements in reducing the number of people who abuse drugs that are prescribed to someone else.

The prescribing guidelines are accessible online at: http://www.massmed.org/Patient-Care/Health-Topi- cs/Massachusetts-Medical-Society-Opioid-Therapy- and-Physician-Communication-Guidelines/#.VWdg 5cvnaic. The public education materials will be available on the Massachusetts Medical Society's Web site in early June. They will be available to anyone who wishes to put them in their offices or share them electronically.

“There is no more important public health issue today than the opioid epidemic,” said Dr. Dimitri. “It is devastating communities, families, men, women, rich and poor, and most tragically, children and adolescents. It has to stop—and physicians are ready to do our part.”

MEDICAL MARIJUANA FOR PAIN EVIDENCE SPARSE: SOME STUDIES SHOW EFFICACY, MORE NEEDED

With increasing numbers of chronic pain patients experimenting with marijuana to get relief, physicians need to learn more about the plant and its constituents to counsel patients appropriately about its safety and possible analgesic benefits, according to a leading medical marijuana researcher speaking on May 15 in a plenary session at the American Pain Society Annual Scientific Meeting. Mark Ware, MD, executive director, Canadian Consortium for the Investigation of Cannabinoids, and director of clinical research, Alan Edwards Pain Management Unit, McGill University Health Center, moved to Canada in 1999 following a court decision that legalized marijuana there. He had been working in Jamaica at a sickle cell anemia clinic, where he encountered several patients who told him that using marijuana eased their pain. At McGill University, Ware evaluates claims from patients about the medical benefits of marijuana and is involved in research on the long-term safety of the plant in patients using it for chronic conditions.

“Much of what we know about medical marijuana is anecdotal, so the challenge is to recognize that patients who say they get pain relief by self-medicating with marijuana may be right, and move forward in conducting more scientific studies to better understand its analgesic benefits and overall safety,” said Ware.

The New York Times has reported that worldwide some 15 trials of medical cannabinoids have been conducted. Results have shown effectiveness in reducing pain from neuropathy, diabetes, and fibromyalgia.

The Food and Drug Administration (FDA) has approved two cannabinoid medications, dronabinal and nabilone. They are prescribed for controlling nausea and vomiting caused by chemotherapy and to treat anorexia in human immunodeficiency virus (HIV) patients. Other cannabinoid-based medications are under FDA review for treating cancer pain and other conditions.

Ware said several challenges lie ahead for conducting marijuana pain studies. “With legalization of medical marijuana in more than 20 states, widespread access will yield more reports that need to be evaluated,” said Ware. “And, while it's clear that large, Phase 3 clinical trials are needed to better understand medical marijuana's potential clinical efficacy, who will pay for them and is it necessary to conduct trials for every pain condition that could be treated with marijuana?”

Another obstacle for medical marijuana research, according to Ware, is lack of standardized products. “Plants grown in Colorado and other legalization states could be different, so when talking about cannabis in various states, there could be a variety of compounds,” he said. According to the National Institute on Drug Abuse, most marijuana used as medicine is the same quality and carries the same health risks as marijuana sold on the street.

New studies also are needed to explore safety problems. “There are safety concerns about the molecule itself, and studies of recreational marijuana users show the drug can affect the brain and lungs. Questions also arise about smoking as a safe route of administration vs. oral dosing,” Ware stated.

In states where medical marijuana is legal, physicians have discretion in advising patients about using it for pain management. “Doctors are being asked every day if using marijuana can lessen pain intensity,” said Ware. “Even though there are no efficacy and safety data from large controlled clinical trials, doctors interested in medical marijuana should learn about the plant itself and its myriad active ingredients by reviewing the scientific literature, understanding local legal issues and potential liability, and weighing the risks and benefits vs. other analgesics, including opioids.”

FIVE PAIN SPECIALISTS RECEIVE PRESTIGIOUS AWARDS

The Canadian Pain Society honored the International Association for the Study of Pain (IASP) past president Fernando Cervero, MD, PhD, DSc, with its Distinguished Career Award and former IASP Councilor Celeste Johnson, RN, DEd, with its Outstanding Pain Mentorship Award at the group's 36th Annual Scientific Meeting in April. Cervero, director of the Alan Edwards Centre for Research on Pain at McGill University, delivered a keynote lecture, “What We Have Learned and What We Still Don't Know About Visceral Pain.”

The German Research Foundation has announced that pediatric pain and palliative medicine researcher Boris M. Zernikow, MD, is the winner of this year's Communicator Award, the most important prize for science communication in Germany. Recognized “for his dedicated and varied public outreach work on pain, pain therapy, and palliative care in children and adolescents,” Zernikow receive the award on June 30 at the foundation's annual meeting. The Communicator Award, which comes with a prize of €50,000, is presented to scientists and scholars who communicate their research and that of their field in a varied, original, and lasting way to the media and the public. Zernikow holds a chair in pediatric pain and palliative care at the University of Witten/Herdecke in Datteln, near Düsseldorf, Germany.

At its annual meeting in March, the American Academy of Pain Medicine recognized Samir K. Ballas, MD, FACP, and Perry G. Fine, MD, for exceptional service to the academy and the field of pain medicine. Ballas is the recipient of the Patient Advocacy Award, which honors health care professionals whose deeds reflect their recognition of the importance and impact of the specialty of pain medicine. Fine received the Distinguished Service Award for his commitment and outstanding contributions to the American Academy of Pain Medicine. Ballas is the author of Sickle Cell Pain, second edition, published in 2014 by IASP Press.

FDA LAUNCHES REMS DATABASE FOR PROGRAM PARTICIPANTS

The Food and Drug Administration (FDA) on June 15 launched the database REMS@FDA. Accessible from www.fda.gov/rems (accessible online at: http://www.accessdata.fda.gov/scripts/cder/rems/ind- ex.cfm), REMS@FDA provides a searchable and sortable information on current FDA-approved risk evaluation and management strategy (REMS) programs. The “What do participants need to do?” link on the site for each listed drug can be used to access information specific to all users of and participants in any REMS program. Also included are links to a drug's prescribing information and Medication Guide (at DailyMed), regulatory information (at Drugs@FDA), and REMS material. The “Contact Us” link at the database's main Web page provides a means by which users can submit comments about REMS@FDA to the agency and ask questions.

FEW DOCTORS CONFIDENT MANAGING PATIENTS ON OPIOIDS

Only a quarter of physicians who prescribe opioids say they are very confident managing the patients they prescribe them to, according to new survey results released by the Boston University School of Medicine (BUSM) and myCME, Haymarket Medical Education's global medical education Web site, on June 2, 2015. Daniel Alford, MD, director of BUSM's Safe and Competent Opioid Prescribing Education (SCOPE of Pain) program, said, “This indicates a critical need for provider education addressing this issue. It is important our medical community is given the training it needs to confidently manage chronic pain while significantly reducing prescription opioid misuse, overdose and diversion.”

The majority of the physicians surveyed agree. More than 90% say being knowledgeable about opioid therapy is an important issue. Many have also taken proactive steps to improve their opioid prescribing practices. Sixty-five percent have implemented systems to support the safe initiation, monitoring, and discontinuing of chronic opioid therapy. Of those that have not implemented such systems, more than 60% said it was not a priority given limited time. Alford said, “It's troubling that so many physicians say implementing safe opioid prescribing systems is not a priority, even though this is an acute issue. We've created a situation where some physicians are comfortable not doing anything about it. That's why education is so critical.”

Creating better awareness of online training opportunities is part of the solution. More than 46% of physicians who completed continuing education on safe opioid prescribing completed it online. “Accessibility is something clinicians value,” Alford said. “That's why BUSM and others have created training programs online so opioid education is available whenever and wherever they are.”

Full survey results are available in the white paper “Provider Perceptions on Opioid Therapy for Chronic Pain.” The white paper is being released in conjunction with a free Trainer's Toolkit for safe opioid prescribing (available online at: www.scopeofpain.com/toolkit) that BUSM has developed to provide residency program directors, chief medical officers, and other physician-leaders several options to effectively and efficiently train their faculty/staff on safe opioid prescribing, specifically around communication with patients. All physicians who were queried are members of myCME. The 804 respondents represent various specialties, including internal medicine, family medicine, emergency medicine, pediatrics, and OB/GYN.

CGRP ANTAGONISTS OFFER PROMISE IN PREVENTING MIGRAINE ATTACKS

Migraine researchers and clinicians are growing 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. Peter J. Goadsby, MD, PhD, who is chair of the scientific program of the American Headache Society's Annual Scientific Meeting in June and Chief of the University of California at San Francisco (UCSF) Headache Center, said the following: “This development is a transformative moment in migraine treatment,” and one of the world's leading headache treatment experts and researchers. “There's no question that we need something better. In fact, for prevention we really need something designed specifically for migraine,”

Goadsby noted that there has not been a new class of antimigraine drugs since the development and marketing of triptans in 1991 and they are not preventives, just designed to treat migraine attacks.

“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,” he said.

Scholarly papers on CGRP and on the trials are being presented this week at the meeting, which draws more than 1000 migraine specialists from around the world. The new class of therapeutic agents appears to reduce elevated levels of the peptide known as calcitonin gene–related peptide (CGRP), a key driver of migraine pain. Versions of anti-CGRP therapies are being tested by Alder Pharmaceuticals, Amgen, Eli Lilly and Company, and Teva Pharmaceuticals.

In Phase IIb trials (studies conducted in patients with migraine) data presented at the American Headache Society meeting by Teva reported for the first time that its drug, as a preventive treatment of high-frequency episodic migraine, achieved a significant reduction in the number of headache hours after 1 week, with more than half of patients in each arm experiencing a 50% or greater reduction in headache frequency. Lilly presented, for the first time, Phase II data in episodic migraine that establishes the efficacy of their medicine against placebo with monthly administration across a range of doses. Amgen presented Phase II data for its anti-CGRP product that showed that the drug reduced the number of migraine days by 50% in about half the treated patients after 12 weeks. Alder Pharmaceutical, the fourth player in the CGRP race, is also developing an anti-CGRP drug with positive phase II data published, and did not present further data at the meeting.

“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,” Dr. Goadsby said. “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.”