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First Long-Term Study on Medical Marijuana’s Impact on Opioid Use for Pain

The National Institutes of Health (NIH) has awarded researchers at Albert Einstein College of Medicine and Montefiore Health System a five-year, $3.8 million grant for the first long-term study to test whether medical marijuana reduces opioid use among adults with chronic pain, including those with HIV.

Millions of Americans experience chronic, severe pain as a result of their health conditions.  Many take prescribed opioids, including Oxycodone, to help relieve their symptoms. But given the dangers of opioid use and misuse, both doctors and patients are seeking safe and effective alternatives to manage pain.

“There is a lack of information about the impact of medical marijuana on opioid use in those with chronic pain,” says Chinazo Cunningham, M.D., M.S., associate chief of general internal medicine at Einstein and Montefiore and principal investigator on the grant. “We hope this study will fill in the gaps and provide doctors and patients with some much needed guidance.”

Compared to the general population, chronic pain and opioid use is even more common in people with HIV. Between 25 and 90 percent of adults with HIV suffer from chronic pain. Previous studies have reported that despite the high risk for misuse of opioid pain relievers, adults with HIV are likely to receive opioids to help manage their pain. In recent years, medical marijuana has gained recognition as a treatment option. Twenty-nine states, plus the District of Columbia, have legalized its use; in those states, chronic pain and/or HIV/AIDS are qualifying conditions for medical marijuana use.

Researchers have never studied—in any population—if the use of medical marijuana over time reduces the use of opioids. Additionally, there are no studies on how the specific chemical compounds of marijuana, tetrahydrocannabinol (THC) and cannabidiol (CBD), affect health outcomes, like pain, function, and quality of life. Most studies that have reported negative effects of long-term marijuana use have focused on illicit, rather than medical, marijuana.

“As state and federal governments grapple with the complex issues surrounding opioids and medical marijuana, we hope to provide evidence-based recommendations that will help shape responsible and effective healthcare practices and public policies,” notes Dr. Cunningham.

Dr. Cunningham will enroll 250 HIV-positive and HIV-negative adults with chronic pain who use opioids and who have received certification from their physicians to use medical marijuana, which is provided through approved dispensaries in New York State. Over 18 months, the study subjects will complete web-based questionnaires every two weeks, which will focus on pain levels and the medical and illicit use of marijuana and opioids. They’ll also provide urine and blood samples at in-person research visits every three months. In addition, in-depth interviews with a select group of these participants will explore their perceptions of how medical marijuana use affects the use of opioids.

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Promising new therapeutic approach for debilitating bone disease

An Australian-led research team has demonstrated a new therapeutic approach that can re-build and strengthen bone, offering hope for individuals with the debilitating bone cancer, multiple myeloma.

The findings were published today in the medical journal Blood, and were presented at an international meeting of bone biology experts in Brisbane earlier this month.

The researchers tested a new type of treatment that specifically targets a protein called sclerostin, which in healthy bones is an important regulator of bone formation. Sclerostin halts bone formation, and the researchers speculated that if they could inhibit the action of sclerostin, they could reverse the devastating bone disease that occurs with multiple myeloma.

Dr Michelle McDonald and Professor Peter Croucher, of the Bone Biology Division of the Garvan Institute of Medical Research in Sydney, led the study.

“Multiple myeloma is a cancer that grows in bone, and in most patients it is associated with widespread bone loss, and recurrent bone fractures, which can be extremely painful and debilitating,” says Dr McDonald.

“The current treatment for myeloma-associated bone disease with bisphosphonate drugs prevents further bone loss, but it doesn’t fix damaged bones, so patients continue to fracture. We wanted to re-stimulate bone formation, and increase bone strength and resistance to fracture.”

The new therapeutic approach is an antibody that targets and neutralises sclerostin, and in previous clinical studies of osteoporosis, such antibodies have been shown to increase bone mass and reduce fracture incidence in patients.

The researchers tested the anti-sclerostin antibody in mouse models of multiple myeloma, and found that not only did it prevent further bone loss, it doubled bone volume in some of the mice.

Dr McDonald says, “When we looked at the bones before and after treatment, the difference was remarkable – we saw less lesions or ‘holes’ in the bones after anti-sclerostin treatment.

“These lesions are the primary cause of bone pain, so this is an extremely important result.”

The researchers have a biomechanical method to test bone strength and resistance to fracture, and found that the treatment also made the bones substantially stronger, with more than double the resistance to fracture observed in many of the tests.

They then combined the new antibody with zoledronic acid, a type of bisphosphonate drug, the current standard therapy for myeloma bone disease.

“Bisphosphonates work by preventing bone breakdown, so we combined zoledronic acid with the new anti-sclerostin antibody, that re-builds bone. Together, the impact on bone thickness, strength and resistance to fracture was greater than either treatment alone,” says Dr McDonald.

The findings provide a potential new clinical strategy for myeloma. While this disease is relatively rare, with approximately 1700 Australians diagnosed every year, the prognosis is extremely poor, with less than half of those diagnosed expected to survive for more than five years.

Prof Croucher, Head of the Bone Biology Division at Garvan, says that preventing the devastating bone disease of myeloma is critical to improve the prognosis for these people.

“Importantly, myelomas, like other cancers, vary from individual to individual and can therefore be difficult to target. By targeting sclerostin, we are blocking a protein that is active in every person’s bones, and not something unique to a person’s cancer. Therefore, in the future, when we test this antibody in humans, we are hopeful to see a response in most, if not all, patients,” Prof Croucher says.

“We are now looking towards clinical trials for this antibody, and in the future, development of this type of therapy for the clinical treatment of multiple myeloma.

“This therapeutic approach has the potential to transform the prognosis for myeloma patients, enhancing quality of life, and ultimately reducing mortality.

“It also has clinical implications for the treatment of other cancers that develop in the skeleton.”

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Q BioMed Closes on Licensing Agreement for FDA Approved Drug – vows no price hike

Q BioMed Inc., a New York-based biotechnology acceleration company recently acquired a FDA approved generic drug, Strontium Chloride (“SR89”). This licensed radiopharmaceutical agent is indicated for the treatment of pain associated with metastatic bone cancer. SR89 provides long lasting relief for patients suffering from bone pain due to metastatic cancer, typically caused by advanced-stage breast, prostate or lung cancer.

The drug is preferentially absorbed in bone metastases, it has been proven to provide a long-term effect resulting in non-narcotic cancer pain relief and enhanced quality of life.

The Company’s immediate efforts and resources will focus on the material procurement and manufacturing process as well as preparing the marketing plan and distribution strategy. The drug is expected to be revenue ready within a short time frame and Q BioMed’s aim is to generate sales within the first year.

According to the Company in a recent press release, “We will make every effort to make this drug as widely available as possible and ensure that the drug will be priced competitively at a cost to patients that is lower than what they are currently paying. In the current environment of skyrocketing drug and medical costs, we believe this is a welcome deviation from the recent headlines. Further, we believe there is an opportunity to invest additional resources into the program to grow the revenue potential significantly. We look forward to making additional details available as soon as practical.”

There are approximately 300,000 new cases of bone metastases in patients with breast and lung cancer per year in the U.S. alone. Approximately 80% of patients using SR89 have reported experiencing a substantial decrease in pain, an increase in physical activity and a reduction in the need for opiate analgesics, such as morphine.

Denis Corin, CEO of Q BioMed Inc. said, “We are very excited about the potential for this drug and look forward to bringing it to market as quickly as possible, delivering significant value to all stakeholders, including current and future patients. The revenue we hope to realize will be a significant milestone for us and substantially derisks our business. However, over and above the near term revenue, we are particularly enthusiastic about the opportunities for growth to increase the potential revenue exponentially. “

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Montefiore and Einstein Researchers Leverage Social Media to Uncover New Data on Migraine Sensory Experiences

A highly trafficked social media forum is yielding new findings on migraine symptoms, according to clinical researchers from the Montefiore Headache Center and Albert Einstein College of Medicine. A new report, “Special sensory experiences in migraine: a social media study,” reveals important disease epidemiology on migraine experiences like olfactory hallucinations, which may not be uncovered during traditional doctor/patient communications. Data from this study will be presented at the 58th Annual Meeting of the American Headache Society (AHS) being held June 9 – June 12 in San Diego.

Migraine ranks in the top 20 of the world’s most disabling medical illnesses, yet is underreported. While hallucinations around certain odors, noises and tastes have been known to occur during a migraine, these symptoms are not included in the International Headache Society classification. To garner more insights into these manifestations, researchers at Montefiore and Einstein tapped The Daily Migraine, a consumer-facing online forum to query 678 respondents through Facebook, Instagram and Twitter three times over three weeks, revealing new insights about experiences with certain tastes, sounds or smells in association with migraine attacks. Queries around olfactory hallucinations, most notably unpleasant smells like cigarette smoke and animal scents were what those with migraine most searched online. Queries also revealed ringing as the predominant migraine-associated sound. Unpleasant tastes, specifically a metallic taste, were also commonly searched.

“As researchers we have only scratched the surface of the depth of patient experience and disease information we can glean from social media channels,” said Matthew S. Robbins, M.D., FAHS, study author and director, Inpatient Services, Montefiore Headache Center, chief of Neurology, Jack D. Weiler Hospital and associate professor of Clinical Neurology, Einstein. “Using social media as a research tool, we learned more about migraine symptoms and what should be included during intake evaluations.”

The magnitude of migraine disability on everyday life causes missed work days, missed opportunities and events spent among family and friends, and can undermine the emotional, social and financial fabric of a family. A recent report published in Mayo Clinic Proceedings, from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, found that approximately 41% of people with migraine and 23% of spouses stated that they believed those impacted by migraine would be better parents if they did not have migraine, which consequently led to half of migraineurs missing at least one family activity in the past month.

“Given the onerous physical and emotional impact of migraine, an online forum is a unique resource to the professional headache community to help us improve how we diagnose, care for and treat headache and facial pain syndromes,” said Cynthia Armand, M.D., study author and chief resident, Department of Neurology, Montefiore and Einstein. “For individuals affected by these neurological diseases, an online site may provide more anonymity and a community, making it a safe place to be open and honest without fear of being judged or marginalized.”

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Narcotic painkillers prolong pain in rats, says CU-Boulder study

The dark side of painkillers – their dramatic increase in use and ability to trigger abuse, addiction and thousands of fatal overdoses annually in the United States is in the news virtually every day.

Brace for another shot across the bow: Opioids like morphine have now been shown to paradoxically cause an increase in chronic pain in lab rats, findings that could have far-reaching implications for humans, says a new study led by the University of Colorado Boulder.

Led by CU-Boulder Assistant Research Professor Peter Grace and Distinguished Professor Linda Watkins, the study showed that just a few days of morphine treatment caused chronic pain that went on for several months by exacerbating the release of pain signals from specific immune cells in the spinal cord. The results suggest that the recent escalation of opioid prescriptions in humans may be a contributor to chronic pain, said Grace.

“We are showing for the first time that even a brief exposure to opioids can have long-term negative effects on pain,” said Grace, who is a faculty member along with Watkins in CU-Boulder’s Department of Psychology and Neuroscience. “We found the treatment was contributing to the problem.”

A paper on the study was published May 30 in the Proceedings of the National Academy of Sciences.

The study showed that a peripheral nerve injury in rats sends a message from damaged nerve cells to spinal cord immune cells known as glial cells, which normally act as “housekeepers” to clear out unwanted debris and microorganisms. The first signal of pain sends glial cells into an alert mode, priming them for further action.

“I look at it like turning up a dimmer switch on the spinal cord,” said Grace.

When the injury was treated with just five days of opioids the glial cells went into overdrive, triggering a cascade of actions, including spinal cord inflammation. Watkins said the initial pain signals to the spinal cord and the subsequent morphine-induced treatment is a two-hit process, which she likened to slapping a person’s face.

“You might get away with the first slap, but not the second,” she said. “This one-two hit causes the glial cells to explode into action, making pain neurons go wild.”

The team discovered that the pain signals from a peripheral injury combined with subsequent morphine treatment worked together to cause a glial cell signaling cascade. The cascade produces a cell signal from a protein called interleukin-1beta (IL-1b), which increases the activity of pain-responsive nerve cells in the spinal cord and brain. That can cause increases in pain duration lasting several months.

“The implications for people taking opioids like morphine, oxycodone and methadone are great, since we show the short-term decision to take such opioids can have devastating consequences of making pain worse and longer lasting,” said Watkins. “This is a very ugly side to opioids that had not been recognized before.”

Roughly 20,000 Americans died in 2015 from overdoses of prescription opioid pain relievers, according to the National Institute on Drug Abuse.

On the up side, the researchers have found ways to block specific receptors on glial cells that recognize opioids. This could allow for some pain relief while potentially preventing chronic pain. The team used a designer drug technology known as DREADD to selectively turn off targeted glial cells, something that has not been done before, said Grace.

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New Study Shows Common NSAIDs can cause more Harm than Good

Many patients around the world, are prescribed non-steroidal anti-inflammatory drugs (called NSAIDs) for the treatment of painful conditions, fever and inflammation. But the treatment also comes with side effects, including the risk of ulcers and increased blood pressure. A major new study from Denmark complied new research that demonstrated that a common arthritis medicine is particularly dangerous for heart patients.

The study also uncovered that older types of arthritis medicine, which have not previously been in focus, also appear to be dangerous for the heart. The study, which was carried out in collaboration between 14 European universities and hospitals, including a number of leading European heart specialists, was published in the most prestigious European journal of heart medicine, European Heart Journal.

“It’s been well-known for a number of years that newer types of NSAIDs – what are known as COX-2 inhibitors, increase the risk of heart attacks. For this reason, a number of these newer types of NSAIDs have been taken off the market again. We can now see that some of the older NSAID types, particularly Diclofenac, are also associated with an increased risk of heart attack and apparently to the same extent as several of the types that were taken off the market,” says Morten Schmidt, MD and PhD from Aarhus University, who is in charge of the research project.

Global Issue Around the World

Pain medications for osteoarthritis account for billions of dollars in annual sales globally. Most pain medications for osteoarthritis, including celecoxib which had global sales of $2.7 billion in 2014, are NSAIDs which have the side effect of elevating blood pressure, and increasing the risk of heart attacks, strokes and death. Of the 27 million Americans who live with osteoarthritis, 13.5 million also suffer from hypertension, which also increases the risk of heart attack, stroke, and death.

Late last year, a new NSAID candidate KIT-302 from Kitov Pharmaceuticals showed good promise as a combination pill that simultaneously treats joint pain and elevated levels of blood pressure. Kitov’s NSAID is a combination of celecoxib and the calcium channel blocker amlodipine.  In Kitov’s phase 3 study, this combination was documented to lower blood pressure better than amlodipine alone, thus enhancing the cardiovascular safety of the amlodipine. In contrast, and consistent with multiple prior publications, celecoxib alone raised blood pressure: An effect that correlates with an increased adverse cardiovascular event rate.

“The primary efficacy of the trial was to show that a combination of the two components of KIT-302, lowers daytime systolic blood pressure by at least 50 percent. Recognizing the cardiovascular dangers associated with NSAID use, Kitov has been working to bring a safer NSAID to market for the past three years,” explained Kitov’s Chairman and Chief Medical Officer, Dr, Paul Waymack.

“Many European countries consume more of these drugs than Denmark. But we can still do better and it’s often the case that paracetamol, physiotherapy, mild opioids or other types of NSAIDs with less risk for the heart would be better for the patients. Of course, the recommendations that have been introduced following our study and its review of the heart-related risks are a big step in the right direction in relation to patient safety,” says Morten Schmidt.