Canada Seeks Feedback on Proposed Opioid and Cannabis Guidelines

By Pat Anson, PNN ditor

Health officials and pain management experts in Canada are seeking public feedback on proposed changes to Canada’s 2017 opioid prescribing guideline. They’re doing it through an online survey, with responses accepted not only from Canadians, but from providers, patients, caregivers and policymakers in the United States and other countries.

“We are very happy to receive feedback from both Canadians and Americans,” says Jason Busse, DC, a clinical epidemiologist and professor of anesthesia at McMaster University. “We are still in the process of drafting the guidelines, as the feedback we receive will affect these documents.”

Busse is leading a panel at McMaster’s Michael G. DeGroote National Pain Centre that has developed 11 draft recommendations for a revised opioid guideline. Survey respondents are being asked whether they agree or disagree with the recommendations, which focus on whether opioids should be a first line treatment for people with chronic non-cancer pain.

Consistent with the current guideline, the panel believes there are several non-opioid treatments that are just as effective as opioids and have less risk of adverse events. It also strongly recommends that opioids not be given to people with a history of opioid overdose, substance abuse, or mental health problems. For pain sufferers without such a history, the panel recommends “discussing a trial” of opioids if nonopioid treatments haven’t lessened their pain.

If opioids are prescribed, the panel suggests avoiding daily doses higher than 80 morphine milligram equivalents (MME), and strongly recommends against doses higher than 150 MME.  The estimated risk of a fatal overdose at 80 MME is relatively low at 0.23% (2.3 overdoses for every 1,000 people) and at 150mg MME is 0.5% (5 in 1,000).

The 80/150 MME recommendations are a substantial change from Canada’s current guideline, which suggest that initial doses of opioids be less than 50 MME and that they not exceed 90 MME.

For people in pain who are stable on long-term opioid therapy, the panel recommends that clinicians “initiate a discussion” of tapering to a lower dose, potentially including discontinuation. If the patient refuses, the panel recommends that another “discussion” be repeated every 6 to 12 months. Forced or involuntary tapering is not recommended.

“The Guideline Panel has formulated their recommendations based on current evidence and the values and preferences of people living with chronic pain. We are seeking public feedback on the current wording of the recommendations and associated remarks. We will review all feedback received in order to further optimize the wording and clarity of the recommendations and remarks,” Busse said in an email to PNN.

To take the opioid survey, click here.

Medical Cannabis Survey

A second survey is also being conducted by the National Pain Centre to help formulate a Canadian guideline for treating chronic pain with medical cannabis. As with the first survey, this one is open to everyone, regardless of where they live.

There are currently four draft recommendations for cannabis. The panel recommends a “trial of cannabis” for chronic pain only if a patient has tried other therapies that haven’t worked. The panel says there is evidence of small improvements in pain, physical function and sleep when cannabis was used.

Smoking cannabis is not recommended. The panel suggests that patients start with low doses of cannabis taken orally in oils and soft gels or inhaled through a vaporizer. Doses can be increased, depending how a patient responds.

Another recommendation is that cannabis be used by patients as a substitute for opioids or to help taper them to lower doses. The panel says “there is little to no difference” in effectiveness between cannabis and opioids, but that cannabis has far less risk of adverse events.

To take the cannabis survey, click here.  

Both surveys will take about 20 minutes to complete and will remain open until 12pm ET, February 29, 2024.

Study Finds Low Risk of Overdose From Prescription Opioids

By Pat Anson, PNN Editor

A large new study that identifies the top risk factors for an overdose involving prescription opioids has inadvertently shown just how low the risk is in the first place.

In a systematic review published in the Canadian Medical Association Journal, researchers at McMaster University looked at 28 studies involving nearly 24 million patients in the United States, Canada and the United Kingdom who were prescribed opioids for chronic pain.

They found 10 “predictors” associated with a higher risk of a fatal or nonfatal overdose, such as a patient taking high doses, having a substance abuse problem, and having multiple prescribers or pharmacies.

Many of these risk predictors are already well-known. What’s different about this study is that the researchers calculated the odds of an overdose happening in different situations and doses. That’s where things get interesting:

“High-certainty evidence from 14 studies involving 1,315,173 patients showed a linear dose–response relationship with opioid overdose. The association was small at a 50-mg morphine equivalent dose/day (OR 1.69, 95% CI 1.50–1.90) and large at 90 mg (OR 2.57, 95% CI 2.08–3.18), with an absolute risk 2.6 per 1000 for fatal overdose and 5.1 per 1000 for nonfatal overdose at a 90-mg morphine equivalent dose/day.”

In plain English, the risk of a fatal overdose at 90 morphine milligram equivalents (MME) is not “large.” It’s only 0.26% at 90 MME, which is considered a fairly high dose. The risk of a fatal overdose is even lower at 50 MME – just 0.16% -- a level that researchers say is “small-to-trivial.”

I’m not a statistician, but 0.26% and 0.16% seem like pretty small odds – similar to the lifetime risk of dying in a car accident, fire or drowning. Unlike opioids, there is no talk of a ban on swimming pools, motor vehicles or matches.

“I think that most people living with chronic pain would agree with your interpretation,” says co-author Jason Busse, DC, a clinical epidemiologist and professor of anesthesia at McMaster University. “I do think, however, that a minority of patients will place greater value on the possibility of overdose and death even though the absolute risk is small.”

Busse’s involvement in the study is notable, because he was the lead investigator in Canada’s 2017 opioid guideline, which suggest that initial doses of opioids be kept under 50 MME and strongly recommend that they never exceed 90 MME. The CDC opioid guideline in the United States makes similar recommendations.

Given the small risk of an overdose actually happening at 50 or 90 MME, the new study would seem to debunk both guidelines. Busse sees it a bit differently, telling me by email that the overdose calculations will help patients understand the risks associated with prescription opioids.

“Our work in this area has suggested that most people living with chronic pain, who have not found sufficient relief with non-opioid therapy, would be interested in a trial of opioids. Specifically, when provided with the evidence for benefits and harms, including the risk of overdose, that most patients in whom non-opioid therapy has proven insufficient would elect to pursue a trial of opioid therapy,” Busse said.

“By presenting the evidence to patients, and helping them to understand the anticipated benefits and harms, we can help ensure that the decisions they make are the right ones for themselves.”

Unfortunately, pain patients in the U.S. and Canada don’t get to make decisions for themselves. Decisions are made for them by doctors, pharmacists, regulators, and law enforcement. Patients increasingly have trouble finding a provider willing to treat them or getting a prescription filled at a pharmacy.

And because the “voluntary” opioid guidelines are usually treated as mandatory,  patients who are prescribed opioids are often kept at ineffective low doses that are well below 90 or even 50 MME.

‘Opiods Kill and Opioids Are Bad’

Experts say the low risk of overdose from prescription opioids was established in previous studies, but people got caught up in opioid hysteria and ignored the evidence. The new study, they say, is no different.

“This paper examines well plowed ground and provides no new insight. Quite the contrary, it obfuscates through oversimplification of the problem,” says Stephen Nadeau, MD, a Professor of Neurology at the University of Florida College of Medicine. “The essential message is that opioids kill and opioids are bad.”

Nadeau says Busse and his co-authors ignored factors like genetic differences in opioid metabolism and put too much emphasis on the risk of a patient having multiple prescribers or pharmacies. The latter could simply be a sign that they were abandoned by a doctor or turned away by a pharmacy, not doctor shopping. Statistics mined from databases don’t tell you that.

“This paper takes a rigorous statistical approach to explain what is happening in a highly heterogeneous population in which there is a high probability of misconstruing the sources of variance. I think it would have been OK if published in 2015, but we have learned a thing or two since then and now the paper serves only to obfuscate and mislead,” said Nadeau.

Two findings in the study worth highlighting are that researchers found little risk of an overdose when a patient is co-prescribed opioids with benzodiazepines, sedatives or muscle relaxants – the so-called “Holy Trinity.” The overdose risk is also “small-to-trivial” when a patient is given long-acting opioids instead of short-acting ones. Those findings contradict the recommendations made in the U.S. and Canadian guidelines.

“The opioid crisis has generated interest in identifying patients at higher risk of addiction or overdose and has led to the development of several screening tools; however, these instruments have either not been validated or shown poor psychometric properties,” wrote lead author Li Wang, PhD, a researcher at McMaster University. “Our findings suggest that awareness of, and attention to, several patient and prescription characteristics, may help reduce the risk of opioid overdose among people living with chronic pain.”

One of the co-authors of the study is David Juurlink, MD, a member of Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group. Like several other PROP members, Juurlink disclosed that he has been a paid expert witness in legal cases involving opioids.

Previous studies have also found that the risk of overdose is small — 0.3% — in Medicaid and Medicare patients prescribed opioids for the first time. Another study of Medicare patients found that over 90% had little to no risk of overdosing. Low risk patients had only 0.006% chance of an overdose.

Medical Cannabis Provides Only Minor Relief for Chronic Pain

By Pat Anson, PNN Editor

An international team of researchers has concluded that medical cannabis and cannabinoids do not provide relief to most people with chronic pain, but are of some benefit to others.

The findings, based on a limited review of 32 medical cannabis studies, were published in the journal BMJ. They are the third set of international guidelines released this year to discourage the use of cannabis as an analgesic because clinical evidence is lacking.

“We are hopeful that patients and physicians will find our guideline helpful, and take away that while medical cannabis will not be effective for most people living with chronic pain, it may provide important benefits for a minority of patients,” said lead author Jason Busse, associate director of McMaster University’s Medicinal Cannabis Research Center in Ontario, Canada.

“For example, we found that 10% more patients that used medical cannabis vs. placebo in trials reported an important improvement in pain relief. This means that only one patient of every 10 treated with medical cannabis experienced this improvement.”

Busse and his colleagues said medical cannabis might provide a “small increase” in pain relief, sleep quality and physical function, with a “small to very small increase” in side effects such as dizziness, nausea and cognitive impairment.

It’s important to note that the panel’s recommendations do not apply patients in palliative care or to smoked or vaporized cannabis. The research team, which included a diverse group of physicians, academics and patient representatives, could not find a good quality clinical study that explored the use of inhaled cannabis.

“We hope that such trials will be forthcoming, as cross-sectional data has found many (perhaps the majority of) people living with chronic pain who use cannabis therapeutically use dried flower products that are typically inhaled or vaporized,” Busse told PNN in an email.

“The most robust evidence base is probably for use of cannabidiol (CBD) to help manage certain forms of pediatric epilepsy; however, most patients use cannabis to manage chronic pain and there are important evidence gaps that urgently need to be addressed so that patients can make fully-informed decisions.”

Due to the limited research on inhaled cannabis, the guideline’s recommendations only cover cannabis products such as edibles, sprays, oils and tinctures, which are usually low in tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis that makes people high.

The panel recommended that non-inhaled cannabis or CBD only be used on a trial basis by patients when “standard care” for pain management is not sufficient. The recommendation applies to adults and children with moderate to severe chronic pain caused by cancer, neuropathy, nociceptive pain or nociplastic pain. The latter two categories cover conditions such as osteoarthritis and fibromyalgia.

“Our weak recommendation in favour of a trial of medical cannabis or cannabinoids reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and a willingness to accept a very small to modest risk of mostly self limited and transient harms,” researchers said.

“The panel, including patient partners, believes that there is great variability in how much reduction in pain severity, improvement in physical functioning, or sleep quality each patient would consider important. Patients who place a high value in improving these symptoms by any amount are more likely to pursue a trial of medical cannabis or cannabinoids.”

The researchers recommend that patients start with a low-dose CBD product, and gradually increase the dose and THC level depending on how the patient responds.

Two medical guidelines released earlier this year also take a dim view of cannabis as a pain reliever. The Australian and New Zealand College of Anaesthetists (ANZCA) urged doctors not to prescribe medical cannabis for patients with chronic pain unless they are enrolled in a clinical trial.

The International Association for the Study of Pain also said it could not endorse the use of cannabinoids to treat pain because there was not enough evidence on the safety and efficacy of CBD.

Study Finds Rx Opioids Provide Limited Pain Relief

By Pat Anson, PNN Editor

Prescription opioids relieve pain, improve physical functioning and help people with chronic pain sleep. But the improvements are small and come with side effects such as vomiting.

Those are the findings from a new meta-analysis (a study of studies) published in the Journal of the American Medical Association (JAMA). Researchers at McMaster University in Canada reviewed 96 clinical trials involving over 26,000 participants who received either prescription opioids or a placebo.

The findings do little to resolve the debate over the safety and effectiveness of opioids.

"Despite widespread use, there is not enough known about the benefits and harms of opioids for chronic non-cancer pain," said lead author Jason Busse, DC, a researcher with the DeGroote Institute for Pain Research and Care at McMaster University.

"We found that, compared to a placebo, 12 per cent more patients treated with opioids will experience pain relief, 8 per cent more will notice an improvement in their physical functioning, and about 6 per cent more will find improvement in their sleep quality.”

One expert questioned the designs of the studies used in Busse’s analysis. Because most participants received a relatively low dose of opioids, it’s not surprising such a small number experienced pain relief, according to Stephen Nadeau, MD, a research advisor for the Alliance for the Treatment of Intractable Pain (ATIP).      

“With few exceptions, doses of opioids achieved were low (median dose 45 MME), trials were short, and opioids were rapidly titrated,” said Nadeau, a neurologist at the VA Medical Center in Gainesville, Florida.

“Because the study designs in all but a handful of studies did not remotely emulate clinical practice, it cannot be inferred that the results of this analysis are applicable to management of the general population of patients requiring opioid management of moderate to severe chronic nonmalignant pain.”

None of the opioid studies reviewed by Busse and his colleagues lasted longer than six months and many were considered low-to-moderate quality evidence. But the same thing could be said about virtually every pain reliever on the market. There is no good quality evidence proving that acetaminophen, pregabalin, ibuprofen, gabapentin or any other non-opioid pain medication is safe or effective long-term.

But opioid critics were quick to focus on the Busse study as proof that opioids should rarely be prescribed for pain.

“The findings reported by Busse et al illustrate that most patients who are prescribed opioids for the treatment of chronic noncancer pain will not benefit from those drugs,” wrote Michael Ashburn, MD, and Lee Fleisher, MD, in a JAMA editorial. “Given the clear risk of serious harm, opioids should not be continued without clear evidence of a clinically important benefit.”

But the only significant side effect the Busse study found was a 6% risk of vomiting. The study drew no conclusions about opioids increasing the risk of addiction, overdose and death – although Busse says those risks should not be overlooked.

“Given their risks, modest benefits, and the comparable effectiveness of alternatives, our results support that opioids should not be first line therapy for chronic non-cancer pain," said Busse, a chiropractor who was the lead author of Canada’s opioid prescribing guideline.

The study was funded by the Canadian Institutes of Health Research and Health Canada.