Study Warns of High Risk of Addiction in Medical Marijuana Users

By Pat Anson, PNN Editor

Medical marijuana is often touted as a treatment for chronic pain, but a new clinical trial found cannabis provided no significant improvement to people who took it for pain, anxiety or depression. Marijuana did help people sleep better, but it also raised their risk of cannabis use disorder (CUD).

“There have been many claims about the benefits of medical marijuana for treating pain, insomnia, anxiety and depression, without sound scientific evidence to support them,” says lead author Jodi Gilman, PhD, with the Center for Addiction Medicine at Massachusetts General Hospital (MGH). “We learned there can be negative consequences to using cannabis for medical purposes. People with pain, anxiety or depression symptoms failed to report any improvements, though those with insomnia experienced improved sleep.”

Gilman and her colleagues enrolled 186 people in the study and randomly assigned them to one of two groups. The first group was allowed to immediately obtain a medical marijuana card, while the second group had to wait 12 weeks before getting one. Both groups were allowed to choose their cannabis products at a dispensary, with no limits on the dose or frequency of use.

Participants in the immediate card acquisition group reported significantly more cannabis use in the study period, with nearly one in five (17%) developing CUD symptoms such as craving, tolerance and withdrawal within 12 weeks. The odds of having CUD were nearly 3 times higher in the immediate acquisition group than in the delayed acquisition group.

“This trial showed that CUD can develop at a fast rate within the first 12 weeks of medical marijuana card ownership, suggesting that those with a card may develop CUD at a similar rate as those who use cannabis recreationally and that the (medical) motive for use may not be protective,” researchers reported in in JAMA Network Open.

“Although most cases of CUD onset in the trial were mild, with 2 to 4 symptoms, these symptoms developed over a short, 12-week initial exposure. The most commonly reported CUD symptoms were higher tolerance and continued use despite the recurrent physical or psychological problems caused or exacerbated by cannabis.”

People with anxiety or depression -- the most common conditions for which medical cannabis is sought -- were at significantly higher risk of developing CUD than those with pain and insomnia.

Incidence of Cannabis Use Disorder

SOURCE JAMA NETWORK OPEN

“Our study underscores the need for better decision-making about whether to begin to use cannabis for specific medical complaints, particularly mood and anxiety disorders,” said Gilman, who called for more regulation of medical marijuana.  “There needs to be better guidance to patients around a system that currently allows them to choose their own products, decide their own dosing, and often receive no professional follow-up care.”

Cannabis advocates say Gilman’s findings are at odds with larger observational studies (here, here and here) that found cannabis use disorder declined in states that legalized medical marijuana. They feel the study also lacked detail of CUD symptoms or what impact they had.

“Although the authors stress the notion that those in the card-holders groups were more likely to be diagnosed with symptoms of CUD, they never identify what these symptoms were, their severity, or how disruptive they were to these individuals daily lives and functioning — or even if in fact they were at all,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group. 

“Finally, it should be recognized that virtually all therapeutic agents possess varying safety profiles. Medical cannabis is not innocuous. But its safety profile is far superior to that of many conventional pharmaceuticals for which it can provide an alternative, including opioids and benzodiazepines — even if one is to take these findings at face value.” 

A recent survey found that twice as many Americans are now using cannabis or cannabidiol (CBD) to manage chronic pain than opioid medication.

Medical Cannabis Significantly Reduced Opioid Use by Pain Patients

By Pat Anson, PNN Editor

Pain patients on long-term opioid therapy were able to significantly reduce their use of opioid medication after they started using medical cannabis, according to a small new study.

Researchers at the Institute for Pain Medicine in Pittsburgh followed 115 patients with severe chronic or intractable pain who had consumed opioids for at least six months before trying medical cannabis. Many lived with pain from failed back syndrome or rheumatoid arthritis. Their average daily opioid dose was nearly 50 MME (morphine milligram equivalent).

Patients were allowed to continue taking opioids during an initial trial with cannabis, but agreed to be weaned off opioids if cannabis was used long-term. Researchers encouraged patients to try different formulations and types of cannabis, but to start with low doses of THC and to avoid smoking.

Thirty patients dropped out of the study because cannabis was ineffective or had unwelcome side effects.

Of the 75 patients who continued using cannabis, many were able to taper themselves to a lower dose of opioids. There was an average 67% decrease in MME after one month and a 73% decrease after two months (from 49.9 MME to 13.3 MME).

“The current study’s approach has led to a significant decrement in chronic opioid use for the majority of patients with chronic pain deciding to trial medical cannabis in our clinical setting,” researchers reported in the journal Pain Physician.

“We feel strongly, based on our study, that medical cannabis should only be available for treatment under a physician’s oversight and as part of a treatment strategy which includes compliance monitoring to minimize harms and improve efficacy rates. After discussing the risks, benefits, and potential side effects of chronic opioid therapy with the patient, the authors of this study present medical cannabis, used with the current study’s paradigm, as a potentially effective class of treatment for chronic pain.”

Previous studies have also found an association between cannabis and reduced opioid use, although this is one of the first to measure it through MME.

A 2020 study found that nearly half of chronic pain patients using medical cannabis reported significant improvement in their pain levels. Most were able to reduce or stop their use of opioids.

A recent Harris Poll found that twice as many Americans are using cannabis products to manage their pain than prescription opioids.

With Little Regulation, Many CBD Products Are Mislabeled

By Pat Anson, PNN Editor

CBD (cannabidiol) is being touted as a treatment for nearly everything these days, from pain and anxiety to insomnia and high blood pressure. There’s even talk about CBD as a potential treatment for COVID-19.

But how much do we really know about the CBD edibles, beverages, oils and other products being sold over-the-counter without a prescription? Are the labels accurate? Are they really free of THC (tetrahydrocannabinol), marijuana’s psychoactive ingredient, as some manufacturers claim?

A new study by researchers at the University of Wisconsin School of Pharmacy should give pause to consumers who put their faith in labels and a cannabis industry that is largely unregulated. The researchers bought 39 CBD products from retail stores in southwest Wisconsin and analyzed them in a laboratory.

Their findings, recently published in the journal Epilepsy & Behavior, found that the vast majority of CBD product labels are inaccurate, containing either too much CBD, too little or none at all. And some products that claimed to be “THC Free” contained enough to give you a good buzz, whether you wanted it or not.

“Our data demonstrate that despite warning letters issued by FDA over the past few years a substantial number of readily available CBD formulations continue to be mislabeled,” researchers reported. “In some cases, products labeled as having CBD contained virtually no active ingredient. This was particularly true for the aqueous (beverage) products.”

Of the 21 CBD-infused beverages that were tested, only one was accurately labeled. The vast majority (78%) were “over-labeled” – meaning they contained less than 90% of the CBD they were supposed to have. The rest (14%) were “under-labeled” – meaning they had 110% or more CBD than the label indicated.

Other products tested, such as edibles, oils and transdermal patches, weren’t much better. Only about a third of the oils (36%) were appropriately labeled with the right amount of CBD, and one oil made by HempLucid contained enough THC to cause intoxication if someone consumed less than half a bottle.

“We found that over half of the studied oil-based products contained measurable THC. This may be of concern not only for the potential of adverse, or at least unexpected, CNS effects, but THC contamination may also create difficulty for patients who are subject to testing for illicit drugs by their employers, parole officers, and even by their own providers in some states as a prerequisite for continued prescribing of controlled substances,” researchers warned.

The concern about THC showing up in drug tests isn’t an idle one. A recent study at Massachusetts General Hospital found THC in nearly 80% of the urine samples from patients who reported using CBD products, including some who thought they were only consuming CBD.

A recent study by Leafreport had findings that were similar to the University of Wisconsin study. Out of 221 CBD products tested, 60% didn’t match their label claims. On average, the CBD content was off from the label by nearly 25 percent.

Although the 2018 Farm Bill legalized the use of hemp-based products that contain less than 0.3% of THC, the FDA has yet to adopt new rules to regulate the cannabis industry. The FDA says it cannot issue regulations until more is known about the safety of CBD products, so for now the agency is “monitoring the marketplace” and only rarely taking enforcement action.

The FDA is well aware of the discrepancies in CBD labeling. A 2021 study by the agency of 147 cannabis products found that less than half contained CBD within 20% of their label declarations. But as long as a company doesn’t make therapeutic claims about their CBD products or call them food supplements, the FDA will probably leave them alone, even if their labels are inaccurate.

The Pros and Cons of Medical Marijuana

By Joanna Mechlinski, Guest Columnist

If you live with chronic pain, chances are someone has mentioned medical marijuana to you. And why shouldn’t they? It’s constantly being discussed in the media.

So far, 36 states have legalized medical marijuana, and many have extended the qualifying illnesses to include some chronic pain conditions. A 2021 Pew Research Center survey found that 91% of American adults approve of the use of cannabis for medicinal purposes. And a recent Gallup poll found that over two-thirds of adults believe marijuana should be legal for both medical and recreational use.

So to the average person, trying to be helpful, it might seem that cannabis is a simple and obvious answer to a pain patient’s prayers. Unfortunately, it doesn’t work that way for everyone.

In 2019, my rheumatologist suggested I try medical marijuana. Considering that I’d been living with chronic pain for over fifteen years, thanks to lupus and polymyositis, and tried all sorts of medications and treatments to no avail, I was understandably excited.

Although I’d had my hopes dashed numerous times already, I still continued to feel a tiny bit of hope whenever a doctor suggested something new. Maybe, just maybe, this would be the thing that would help alleviate my life of never-ending pain and fatigue. If so many other people were turning to medical marijuana, surely it had to be a good thing?

Like many other pain patients, I was tired of the constant battle to prove I “deserved” opioid painkillers. I was also tired of never daring to mention the fact that opioids were the main reason I was still a productive member of society. Many people choose to ignore that fact and focus instead on the potential for addiction.

Unfortunately, it’s not as if you can just walk into a marijuana dispensary and be handed a life-altering concoction. There’s a lot more to it, much of which no one ever seems to mention.

For starters, not every medical professional is legally permitted to certify a patient for cannabis, which is required in many states. You need to find a doctor or APRN (advanced practical registered nurse) who is --- and it’s usually not cheap.

Here in Connecticut, the practitioner I saw charged $175 for new patients and $125 for a renewal. Then, along with your application, you need to send the state $100. This gets you a medical marijuana certificate, good for only one year, if you have a “debilitating medical condition” recognized by the state.

Different states charge different prices and your certificate or license can last longer, depending on where you live. There are also some discounts - again, not everywhere - for veterans and low-income individuals. Still, the various costs can add up quickly, and they are not covered by insurance.

Your first visit is a consultation, at which you and a staff member discuss your condition and symptoms. Unfortunately, it’s not a one-size-fits-all kind of thing. Your body may react differently to a particular marijuana strain or product than another person suffering from similar symptoms.

So, if you’re like me, you may have to try a wide variety of tinctures, oils, vapes and other products. Each will cost, on average, between $50-$100 for a few weeks’ dosage. You can only pay with cash or a debit card.

Over two years, I returned to the dispensary numerous times, hoping the next product might be the one. But at best, there was just a slight improvement. I was wanting so badly for cannabis to work that it might have solely been in my imagination.  

At any rate, I wasn’t willing to keep paying large amounts of money for something that was causing me about 5% improvement at best.  More realistically, it was probably closer to zero.

Does all this mean you shouldn’t give medical marijuana a try? Of course not. If you and your doctor feel it may alleviate your pain and is a good option, you should definitely give it a try. Just keep in mind there are a lot of factors to consider, and patience is definitely key to the process.

Joanna Mechlinski is a former journalist who currently works in school transportation. She lives with lupus, polymyositis and fibromyalgia, and is passionate about advocacy. 

Pain News Network invites other readers to share their stories with us. 

Send them to: editor@PainNewsNetwork.org. 

Cannabis Users May Risk Harmful Drug Interactions

By Pat Anson, PNN Editor

A recent survey found that nearly half of American adults (49%) have tried marijuana, a figure that has risen steadily in recent years as more states legalize medical and recreational cannabis. While the Gallup poll didn’t ask people why they used marijuana, it’s fair to say many are experimenting with cannabis products – and cannabidiol (CBD) in particular – as alternatives to mainstream medical treatment.

And that could be a problem for people with chronic pain and other illnesses, according to researchers at Washington State University, who found that CBD interferes with two families of enzymes that help metabolize pain relievers and other drugs prescribed for a variety of medical conditions. As a result, the medications’ positive effects might decrease or the drugs could build up in the body and become toxic.

“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids,” said Philip Lazarus, PhD, a professor of pharmaceutical sciences and senior author of two new studies appearing in in the journal Drug Metabolism and Disposition.

“It’s one thing if you’re young and healthy and smoke cannabis once in a while, but for older people who are using medications, taking CBD or medicinal marijuana may negatively impact their treatment.”

One study focused on enzymes known as cytochrome P450s (CYPs), while the second study looked at enyzymes called UDP-glucuronosyltransferases (UGTs). Together, the two enzyme families help metabolize and eliminate more than 70 percent of the most commonly used drugs from the body.

The WSU researchers studied three cannabinoids — tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) -- and how they interact with CYP and UGT enzymes. Of particular interest to the researchers are the metabolites produced by cannabinoids as they break down in the body.     

“Cannabinoids stay in your body only for about 30 minutes before they are rapidly broken down,” said first author Shamema Nasrin, a graduate student in the WSU College of Pharmacy and Pharmaceutical Sciences. “The metabolites that result from that process stay in your body for much longer -- up to 14 days -- and at higher concentrations than cannabinoids and have been overlooked in previous studies, which is why we thought we should focus on those as well.”

The researchers found that cannabinoids and the major THC metabolites strongly inhibit several key CYP enzymes in the liver that play a role in metabolizing anti-cancer drugs, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, anti-epileptics and other medications. Cannabinoids also inhibited two of the primary UGT enzymes in the liver.

Atlhough the liver is considered the most important organ for the metabolism of drugs, kidneys also play a vital role, clearing toxins and other drugs from the body. Researchers found that CBD blocked three enzymes that account for about 95 percent of kidney UGT metabolism.

“If you have a kidney disease or you are taking one or more drugs that are metabolized primarily through the kidney and you’re also smoking marijuana, you could be inhibiting normal kidney function, and it may have long-term effects for you,” Lazarus said.

The interactions between CBD and UGT enzymes could be especially risky for patients with acute kidney disease, kidney cancer or HIV, who may be using CBD to treat pain or to try to reduce the side effects from anti-cancer drugs.

“Taking CBD or marijuana might help your pain but could be making the other drug you’re taking more toxic, and that increase in toxicity may mean that you can’t continue taking that drug,” Nasrin said. “So, there could be serious ramifications for anti-cancer drugs, and that’s only one example of the many drugs that could potentially be affected by the cannabinoid-enzyme interactions we’re seeing.”

More research is needed to fully understand the drug-drug interactions that cannabis may have. Drugs.com has a list of 387 drugs that are known to interact with cannabis, with 26 categorized as major interactions and 361 described as moderate.

Medications known to have major interactions with cannabis include several opioids, such as codeine, fentanyl, buprenorphine, hydrocodone, methadone, morphine and oxycodone.

Patients and Doctors Finally Talking About Medical Cannabis

By Pat Anson, PNN Editor

Communication is important in every relationship, especially between doctors and patients. And a new survey suggests that the stigma that has long kept cannabis a dirty secret in the exam room may finally be disappearing.   

The survey of 445 healthcare providers who treat chronic pain found that 72% of them have patients who requested or asked about medical cannabis in the last 30 days. Patients asked about cannabis far more often than other alternative pain treatments, such as acupuncture (37%), physical therapy (13%) and massage (10%).

The online survey was recently conducted by Cannaceutica, a healthcare company developing a line of cannabis products to treat pain. A variety of providers participated in the survey, including general practitioners, pain management specialists, neurologists, rheumatologists, and nurse practitioners.

People weren’t always so willing to talk to healthcare providers about cannabis, fearing they’d be seen as pot heads or even be dropped as patients. National surveys conducted in 2018 and 2019 found that less than 40% of patients told their doctors about their cannabis use.  

More patients are talking about cannabis today, and more doctors are willing to listen. The vast majority of providers (81%) in the Cannaceutica survey believe cannabis will play a role in the future management of chronic pain, but only one in four are likely to recommend it now. The primary factors holding them back are legal and regulatory issues, and the lack of good quality cannabis research.

Medical cannabis is legal in 36 states, but remains illegal at the federal level. If cannabis were legalized federally, 74% of providers said they would be likely to recommend it to a patient.

To increase their comfort level about recommending cannabis, providers want to see more research and documentation about cannabis as a pain treatment. Nearly two-thirds (64%) said patients were their main source of information about cannabis, followed by the internet (44%) and medical journals (40%).

Over half the providers surveyed said current treatment options are insufficient to treat chronic pain (56%) and that they were actively seeking alternatives (58%) for their patients. It’s worth noting that pain management specialists were most likely to say current treatments are inadequate (59%) and that they were seeking alternative treatments (66%).  

Clinical Trial Seeks Volunteers

Cannaceutica is currently enrolling chronic pain patients in a clinical trial to test the safety and efficacy of its cannabis capsules, which contain a blend of tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as the cannabinoids cannabichromene (CBC) and cannabigerol (CBG). A recent study found that CBG boosts the potency of cannabis products used to treat chronic pain, depression, insomnia and anxiety.

The observational study is being led by University of California, Irvine researcher Dr. Marcela Dominguez. She and her team hope to enroll 107 patients in the trial, which is expected to last 14 to 16 weeks. They’re looking for people who have experienced pain for at least three months, have tried at least two different medications, and are not currently using cannabis. Patients with fibromyalgia or cancer pain are not eligible to participate.

If you would like to volunteer or get more information in the study, click here.

Exercise Reduces Pain by Increasing Beneficial Bacteria

By Pat Anson, PNN Editor

Regular exercise can benefit people in many different ways, helping us lose weight, reduce the risk of heart disease, and boosting overall health.  

But researchers at the University of Nottingham have found that exercise has an unexpected benefit for people with arthritis. Regular exercise increases levels of beneficial bacteria in their digestive tracts, which reduces pain and inflammation by increasing levels of endocannabinoids – cannabis-like substances naturally produced by the body.

The study, published in the journal Gut Microbes, is believed to be the first to find a potential link between endocannabinoids, exercise and gut microbes.

"Our study clearly shows that exercise increases the body's own cannabis-type substances. Which can have a positive impact on many conditions,” says lead author Amrita Vijay, a Research Fellow at Nottingham’s School of Medicine. "As interest in cannabidiol oil and other supplements increases, it is important to know that simple lifestyle interventions like exercise can modulate endocannabinoids."

Vijay and her colleagues enrolled 78 people in their study. Half of the participants did 15 minutes of muscle strengthening exercises every day for six weeks, and the rest did nothing. Blood and fecal samples were collected from both groups.

At the end of the study, participants who exercised not only had lower pain levels, they also had significantly more Bifidobacteria and Coprococcus 3 -- bacteria that produce anti-inflammatory substances and lower levels of cytokines, which regulate inflammation.

These gut bacteria were particularly adept at raising levels of short chain fatty acids (SCFAs), which increase levels of endocannabinoids. About a third of the anti-inflammatory effects of the gut microbes was due to their ability to raise endocannabinoid levels.

Importantly, the exercise group also had lower levels of Collinsella – a bacteria known to increase inflammation that is strongly associated with processed food and diets low in vegetables.    

“In this study we show that circulating levels of ECs (endocannabinoids) are consistently associated with higher levels of SCFAs, with higher microbiome diversity and with lower levels of the pro-inflammatory genus Collinsella. We also show statistically that the anti-inflammatory effects of SCFAs are up to one third mediated by the EC system,” researchers concluded.

Previous studies have also found an association between gut bacteria and painful conditions. A 2019 study at McGill University found that women with fibromyalgia had 19 different species of bacteria that were present in either greater or lesser quantities than a healthy control group.

Bacteria associated with irritable bowel syndrome, chronic fatigue syndrome and interstitial cystitis were also found to be abundant in the fibromyalgia patients, but not in the control group.    

Having a healthy diet can also affect pain levels for migraine, neuropathy and other types of chronic pain. A recent study funded by the National Institutes of Health found that migraine sufferers who ate more fatty fish and reduced their consumption of polyunsaturated vegetable oils — frequently found in processed foods — had fewer headaches.

More Americans Using Cannabis to Treat Chronic Pain Than Opioids

By Pat Anson, PNN Editor

Twice as many Americans are now using cannabis or cannabidiol (CBD) to manage their chronic pain than opioid medication, according to a new Harris Poll that found significant changes in pain management in the U.S. since the onset of the Covid-19 pandemic.

Over-the-counter pain relievers are used by over half (53%) of those surveyed, followed by cannabis products (16%) and non-opioid pain relievers (11%). Opioid pain medication is being used by only 8% of Americans with chronic pain. Non-drug treatments such exercise, heat/ice and healthy eating are also being widely used to relieve pain.

TREATMENTS USED TO MANAGE CHRONIC PAIN

SOURCE: SAMUELI FOUNDATION

The online survey of 2,063 adults was conducted last month on behalf of the Samueli Foundation. About half the participants said they were currently experiencing chronic pain.

One of the more surprising results is that young adults, aged 18 to 34, are more likely to have chronic pain than older ones (65% vs. 52% of those aged 35 and older).

“It is surprising, but we do know from other research that younger people are less healthy overall than older adults were at their age, so the higher prevalence of pain may be related to that. It seems that younger generations are facing health issues that were not experienced by older generations, causing them to be sicker and in more pain at a younger age,” said Wayne Jonas, MD, executive director of Integrative Health Programs at Samueli Foundation.

“There are a number of factors that could be at play here – and most of them can be attributed to lifestyle factors. Things like a poor diet, a lack of exercise, the growing pace of change and stress and very little self-care can lead to issues with a person’s health – physically, mentally, and emotionally. Chronic pain is a whole person issue with stress and social isolation contributing to its perpetuation. This is an issue that needs to be addressed in this population to ensure that as they age, their health doesn’t become precipitously worse.”

More than one in five young adults who have chronic pain (22%) said they use cannabis and/or CBD oil for pain, and they are twice as likely to do so compared to those aged 45 and older (11%).

“I think it’s clear that young people are looking for ways to manage their pain on their own – through self-care. And CBD and cannabis products are increasingly available and legal. People are feeling like they need to find their own ways to manage their pain because the care provided them may be lacking,” said Jonas, a clinical professor of Family Medicine at Georgetown University School of Medicine and former director of the National Institute of Health’s Office of Alternative Medicine.

The survey found that most adults with chronic pain don’t feel that healthcare providers are giving them adequate information on how to manage their pain. Nearly 80% wished their pain was taken more seriously by providers and 68% wished they had more information about how to treat chronic pain.

That lack of information – and no doubt the decreasing availability of opioids – has led to some experimentation. Two-thirds of Americans with chronic pain (66%) say they have changed their pain management since the pandemic began, such as using more OTC pain relievers and cannabis products. There is also more willingness to use non-drug treatments, such as exercise, healthier eating, massage, physical therapy, and mindfulness or meditation to reduce stress.

About 1 in 4 Americans say stress, anxiety and lack of sleep made their chronic pain worse during the pandemic. The vast majority of people in chronic pain (83%) say their quality of life would greatly improve if they were better able to manage it.

“This should be a wake-up call to physicians that their patients are looking for more information from them about managing their chronic pain, especially for non-drug approaches.” said Jonas.

Cannabis Oil Effective for UK Chronic Pain Patients

By Pat Anson, PNN Editor

Medical cannabis has been legal in the United Kingdom since 2018, but we’re only now getting the first evidence on the effectiveness of cannabis oil for UK chronic pain patients.

One hundred ten patients enrolled in the UK Medical Cannabis Registry reported significant improvements in their pain, discomfort and sleep quality after one, three and six months of treatment with cannabis oil. There was also statistically significant improvement in their health-related quality of life.

Due to strict rules, it is difficult to get a prescription for medical cannabis from the UK’s National Health Service. Patients can only be prescribed cannabis when conventional therapy has not provided adequate relief for conditions such as pain, anxiety and multiple sclerosis.

Most of the patients (65%) in the study had never used cannabis before. Their most common primary diagnosis was chronic non-cancer pain (48%), followed by neuropathic pain (24%) and fibromyalgia (16%).

“With the increasing number of prescriptions for medical cannabis in the UK, capturing patient outcomes and real-world evidence is essential for wider understanding and appropriate access for eligible patients,” Dr. Simon Erridge, head of research at Sapphire Medical Clinics, said in a statement.

“This research is the first of its kind in Europe and we continue to review condition and product-specific outcomes via the UK Medical Cannabis Registry. Though this is still observational data it will inform critical future research including randomised controlled trials.”

Sapphire Medical Clinics created the registry and surveyed patients to help fill some of the gaps in knowledge about medical cannabis. The findings were recently published in the Journal of Clinical Pharmacology.

“Despite promising preclinical data, there is a paucity of high-quality evidence to support the use of CBMPs (cannabis-based medicinal products). The evidence base, while broad, is inconclusive, variable across chronic pain types, and thus insufficient to inform guidelines, funders, and licensing agencies,” researchers said.

The cannabis oil used in the study is made by Adven, a subsidiary of Curaleaf International, Europe’s largest independent cannabis company. The median CBD dose was 20 mg per day, while the median THC dose was 1 mg per day, giving the oil a CBD/THC ratio of 20 to 1. Adverse events such as nausea, dizziness and constipation were reported by nearly a third of patients, with most symptoms being mild or moderate.

Sapphire Medical Clinics is planning further studies of cannabis products as more participants enroll in its cannabis registry.

‘Mother of All Cannabinoids’

Another study conducted in the U.S. found that people who use cannabis products that are rich in cannabigerol (CBG) reported significant improvement in their pain, anxiety, depression and insomnia.

CBG is known as the “mother of all cannabinoids” because it rapidly converts into THC and CBD. Only trace amounts of CBG are found in most cannabis plants, but in recent years cultivated strains rich in CBG have been grown in the Pacific Northwest.

Researchers at Washington State University and the University of California Los Angeles surveyed 127 people who self-identified as consumers of CBG-dominant cannabis. Most reported their pain and other symptoms were “very much improved” or “much improved” by CBG.

About 75% said CBG-predominant cannabis was superior to conventional medications for chronic pain, depression, insomnia and anxiety. A little over half reported minor side effects such as dry mouth, sleepiness, increased appetite, and dry eyes. Most reported no withdrawal symptoms.

“This is the first patient survey of CBG-predominant cannabis use to date, and the first to document self-reported efficacy of CBG-predominant products, particularly for anxiety, chronic pain, depression, and insomnia. Most respondents reported greater efficacy of CBG-predominant cannabis over conventional pharmacotherapy, with a benign adverse event profile and negligible withdrawal symptoms,” researchers reported in the journal Cannabis and Cannabinoid Research. 

“This study demonstrates that CBG-predominant cannabis and related products are available and being used by cannabis consumers and demonstrates the urgent need for randomized controlled trials of CBG-predominant cannabis-based medicines to be studied rigorously to assess safety and efficacy.”

Preliminary research suggests CBG has antibacterial properties and might be useful in treating inflammatory bowel disease (IBD), glaucoma, Huntington’s disease and some forms of cancer.  

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 Marijuana Reduces Pain, but Worsens Self-Care

By Pat Anson, PNN Editor

The 1998 comedy “The Big Lebowski” has a cult-like status as a stoner film, largely because of the way Jeff Bridges portrays a weed-smoking slacker who has no job, can’t pay the rent and spends half the movie in a bathroom robe. The Dude abides life at his own pace.

A new study may have inadvertently reinforced some of that stoner stigma, finding that marijuana use reduces pain but significantly worsens patient “self-care” – a broad category that includes behavior such as motivation, physical activity and appearance.

The study involved 181 pain patients enrolled in Pennsylvania’s medical marijuana program, who used marijuana for eight weeks and regularly completed surveys on its effects.

The study findings, recently published in the journal Medical Cannabis and Cannabinoids, showed that participants reported significant improvement in their pain and anxiety, and a small improvement in quality of life. But there was a caveat.

“One sees that the improvements to the pain and anxiety dimensions are tempered by a decline in the area of self-care. This is important because the side effect profile of cannabis may be diminishing the improvement in (quality of life),” wrote lead author Andrew Peterson, PharmD, University of the Sciences in Philadelphia. “A review of the literature found no other study connecting the use of marijuana with declines in self-care in pain patients using MM (medical marijuana).”

The study did not look at the doses used by participants, but since all products in Pennsylvania’s medical marijuana program contain some level of tetrahydrocannabinol (THC) – the psychoactive substance in marijuana – researchers believe there might be a connection. They said further studies were needed to see if there’s a relationship between THC, self-care and quality of life.

“There are many sources describing the negative consequences of marijuana,” Peterson wrote. “Given that our study found a decline in self-care among pain patients using MM (medical marijuana), it would be of interest to learn what aspects of self-care change when using MM for pain.”

According to the National Institute on Drug Abuse, some of the negative consequences of marijuana use include changes in mood, difficulty with thinking and problem-solving, impaired memory and an altered sense of time.  

CBD Reduced Burnout and Depression in Healthcare Workers

By Pat Anson, PNN Editor

After a year and a half of social distancing, masks and isolation, are you feeling emotionally burned out from the pandemic?

If so, you’re not alone. A recent survey of over 1,000 workers found that over half reported they were fatigued, depressed and had trouble concentrating.  Another study in the UK found that healthcare providers and other essential workers were particularly at risk of depression due to the stress of COVID-19.

With that in mind, researchers at the University of São Paulo in Brazil recently conducted a study to see if daily doses of cannabidiol (CBD) could relieve emotional exhaustion and burnout symptoms in a cohort of 120 frontline healthcare professionals.

Half of the study’s participants received 300mgs of CBD oil daily for four weeks. The other half did not receive CBD. All participants were evaluated weekly by a psychiatrist and encouraged to exercise.

The research findings, published in JAMA Psychiatry, found that participants who received CBD treatment had a significant reduction in emotional exhaustion and burnout compared to those who did not. CBD consumption was also associated with less anxiety and depression, but had no impact on post-traumatic stress syndrome (PTSD).

Five participants in the CBD group dropped out of the trial after suffering from serious adverse events, mostly elevated liver enzymes. Those cases resolved after CBD of discontinued.

“This randomized clinical trial found that the efficacy and safety of daily treatment with CBD, 300 mg, for 4 weeks combined with standard care was superior to standard care alone for reducing the symptoms of emotional exhaustion, anxiety, and depression among frontline health care professionals working with patients with COVID-19,” researchers reported.

“Burnout among health care workers is an important issue for health care systems, with a direct impact on quality of care. No pharmacological treatment is currently available for the prevention or treatment of burnout symptoms and emotional exhaustion among frontline health care professionals working with patients with COVID-19… Therefore, the results of the present study could have a relevant impact on the mental health of health care staff worldwide.”

The researchers said more placebo-controlled trials were needed to assess whether CBD could be used more broadly as a mental health treatment.

Previous studies have also found that medical cannabis reduced symptoms of depression. A 2020 study conducted in New Zealand found that people consuming up to 300mg daily in CBD oil reported significant improvement in their pain, mobility, anxiety and depression. Some also said they slept better and their appetite improved.

Another 2020 study found that 95% people who smoked or inhaled cannabis through a vaporizer reported a decline in depression within 2 hours. Cannabis with high levels of tetrahydrocannabinol (THC) was particularly effective in reducing depression.

My Migraine Journey: From Electrodes to Cannabis

By Gabriella Kelly-Davies, PNN Columnist

The room swirled as my eyes fluttered open, and I could feel something tight around my neck. It felt like a vice, making it difficult to swallow. The antiseptic smell was familiar, but I couldn’t quite place it. Struggling to focus my eyes, I heard a voice I knew well — it was Ben, a doctor at the hospital where I worked as a physiotherapist.

“How do you feel?” Ben said, shining a bright torch into my eyes.

“Where am I?”

“You’re in emergency. An ambulance brought you here. You were lying on the side of the road, unconscious.”

Ben told me the ambulance officers had received reports of cyclists being pushed off their bikes at the quieter end of the beach. They assumed that’s what had happened to me.

That day, my twenty-fourth birthday, heralded the onset of a life of migraine attacks.

Gabriella Kelly-Davies

During the 1990s, I regularly traveled around Australia for work while studying business at night. In the plane as I read my textbooks, a pain like an electric shock would shoot up the back of my neck and head.

It lasted for several minutes, then a deep ache started in the base of my skull. The pain eventually spread upwards, fanning out until it covered the entire back of my head and temples.

All too soon, the pain I experienced while flying became more regular and was most severe after sailing and playing my piano or cello. Cycling and tennis also triggered it.

In 1996, I started a job in Parliament House, Canberra as a policy adviser to a senior politician. Mid-morning, I would feel shooting pains running up the back of my head, accompanied by waves of intense nausea. Soon afterwards, a deep ache in the base of my skull started, quickly spreading up over my head and into my temples. My eyes felt gritty, as if they were full of sand, and I yearned for them to explode to release the mounting pressure inside them.

Often when the pain was at its worst, I couldn’t think of the words I wanted to say, infuriating some colleagues. Sometimes I couldn’t string two words together coherently. My mouth refused to form the words I wanted to say, as if the messages weren’t getting through from my brain to the muscles in my face.

The Merry-Go-Round

Returning to Sydney in 1999, I despaired of ever being free of pain and nausea. I consulted an endless round of specialists and health professionals, but none of them helped much. I felt overwhelmed by head and neck pain and a general sense of ever-increasing pressure inside my head and eyes. I fantasized about boring a hole through the base of my skull with an electric drill to release the tension.

Between 2000 and 2005, I progressively stopped doing all the things I most loved because they triggered migraine attacks. My goal became getting through a day of work, returning home and lying in a dark room with a series of ice packs under my neck.

Anxiety about being stigmatized and the intolerance I perceived in some colleagues at work prevented me from admitting I was in pain. Instead, I worked like a Trojan to ensure I maintained a high level of performance and no one could accuse me of using pain as an excuse to under-perform.  

While on the endless merry-go-round of seeking solutions, I ended up at the Michael J. Cousins Pain Management and Research Centre in Sydney. Dr. Cousins and a team of health professionals assessed me. They diagnosed occipital neuralgia, a form of headache that can activate migraine attacks. I had chronic pain, a malfunction in the way the nervous system processes pain signals.

The team suggested an experimental treatment. It involved implanting tiny electrodes into the back of my head and neck to block the pain signals from traveling along the nerves in my head. I agreed to the surgery and afterwards; I had fewer migraine attacks than previously. I even had a few completely pain-free days.

One year later, I felt something sharp sticking out from the base of my skull. My pain specialist discovered an electrode wire protruding through the skin. Tests revealed the electrodes were infected, so they were removed. Afterwards, migraine attacks returned in full force.

Three months later, new electrodes were implanted, but they didn’t work as well, possibly because scar tissue blocked transmission of the electric current. Still, overall I was better than before the initial surgery. I worked full time and sang in a choir at Sydney Opera House.

Disappointingly, disaster struck in 2008. A superbug infected the electrodes, forcing my doctor to remove them. Once the infection cleared and the electrodes were re-implanted, they were only partially successful, and my life returned to its pre-electrode state.

Multidisciplinary Pain Management

A significant turning point occurred in 2009 when I participated in a three-week multidisciplinary pain management program. Each day, a team of pain specialists gave lectures on topics such as chronic pain and how it differs from acute pain. The physiotherapists started us on a carefully graded exercise program, and a psychologist taught us cognitive behavioural therapy techniques to help us change the way we thought about and dealt with pain. Surprisingly, the exercises didn’t cause a flare-up and at last I felt as if I was making progress.

The pain management program taught me to stop catastrophizing and to believe I had the power to change how I reacted to pain. For years, I practiced the stretches and strengthening exercises every night after work. I also applied the psychological techniques, and they became central to my daily routine.

Twelve years later, I continue to live with migraine. I’ve tried several migraine preventatives, but none helped. Eight months ago, I started taking medicinal cannabis and it has significantly reduced the frequency and severity of migraine attacks.

Over the years I’ve learned to reduce the impact of migraine on my life by using techniques such as mindfulness meditation and carefully paced exercise that turn down the volume of pain signals racing through my malfunctioning nervous system.

Chronic pain is complex and difficult to treat but it is possible to live well with pain. I encourage you to do a multidisciplinary pain management program and continue your search for approaches that reduce the impact of pain on your life.  

Gabriella Kelly-Davies is a biographer and studied biography writing at the University of Oxford, Australian National University and Sydney University. She recently authored “Breaking Through the Pain Barrier,” a biography of trailblazing Australian pain specialist Dr. Michael Cousins. Gabriella is President of Life Stories Australia Association and founder of Share your life story.

Terpenes Make Cannabis More Effective as Pain Reliever

By Pat Anson, PNN Editor

A new study may help explain what makes cannabis effective as a pain reliever. It’s not just cannabinoids like cannabidiol (CBD) or tetrahydrocannabinol (THC), but terpenes -- the aromatic compounds that give cannabis its distinctive “skunky” smell. The finding could lead to new ways to boost the potency of cannabis, opioids and other pain-relieving drugs without increasing the dosage.

In experiments on laboratory rodents, scientists at the University of Arizona Health Sciences found that Cannabis terpenes, when used alone, mimic the effects of cannabinoids, including a reduction in pain sensation. When terpenes were combined with a synthetic cannabinoid, the pain-relieving effects were amplified – an “entourage effect” – that reduced pain levels without an increase in euphoria and other side effects.

"A lot of people are taking cannabis and cannabinoids for pain," said lead researcher John Streicher, PhD, a member of the UArizona Health Sciences Comprehensive Pain and Addiction Center and associate professor of pharmacology at the College of Medicine-Tucson.

"We're interested in the concept of the entourage effect, with the idea being that maybe we can boost the modest pain-relieving efficacy of THC and not boost the psychoactive side effects, so you could have a better therapeutic."

Terpenes are found in many plants and are the main component in essential oils. The terpene linalool gives lavender its distinctive floral scent, while citrus trees get their smell from the terpene limonene. Plants create terpenes to lure pollinators, such as birds and insects, and to protect themselves from predators.

Streicher and his colleagues focused on four Cannabis terpenes: alpha-humulene, geraniol, linalool and beta-pinene. They evaluated each terpene alone and in combination with a synthetic cannabinoid that stimulates the body's natural cannabinoid receptors.

In laboratory experiments, researchers found that all four terpenes activated a cannabinoid receptor in the brain, just like THC. The behavioral studies in mice also revealed the terpenes lowered pain sensitivity, reduced pain sensation, lowered body temperature, and reduced movement and catalepsy, a freezing behavior related to the psychoactive effects of cannabinoids.

When terpenes were combined with the synthetic cannabinoid, researchers saw a greater reduction in pain sensation -- demonstrating a terpene/cannabinoid interaction in controlling pain.

"It was unexpected, in a way," said Streicher. "It was our initial hypothesis, but we didn't necessarily expect terpenes, these simple compounds that are found in multiple plants, to produce cannabinoid-like effects."

The study findings were recently published in the journal Scientific Reports. Streicher and his research team still need to confirm if terpenes have an entourage effect when combined with THC and other naturally occurring cannabinoids. Their long-term goal is to develop a dose-reduction strategy that uses terpenes in combination with cannabinoids or opioids to achieve the same levels of pain relief with fewer side effects.

Although the therapeutic benefits of terpenes are not well understood, some cannabis companies are already incorporating them into their products. Lemon Kush, for example, is a hybrid marijuana strain that contains limonene, while the hybrid Blue Dream has a terpene found in blueberries. Terpenes are also being added to chocolate, beverages and many other consumer products.  

Fibromyalgia Patients Substituting CBD for Pain Medication

By Pat Anson, PNN Editor

With opioid medication increasingly harder to obtain, many people with chronic pain are turning to cannabis-based products for pain relief.  A new survey of fibromyalgia patients suggests that cannabidiol (CBD) works well not only as an alternative to opioids, but for many other pain medications.

Researchers at Michigan Medicine surveyed 878 people with fibromyalgia who were currently using a CBD product and found that 72% of them had substituted CBD for a conventional pain medication.

Over half (59%) reduced or stopped taking non-steroidal anti-inflammatory drugs (NSAIDs), while 53% used CBD as a substitute for opioids, gabapentinoids (35%) or benzodiazepines (23%), an anti-anxiety medication that was once commonly prescribed for pain.

"I was not expecting that level of substitution," said Kevin Boehnke, PhD, a research investigator in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center at Michigan Medicine.

Fibromyalgia is a poorly understood disorder characterized by widespread body pain, fatigue, poor sleep, anxiety and depression. Standard treatments for fibromyalgia such as gabapentinoids often prove to be ineffective or have unwelcome side effects.

"Fibromyalgia is not easy to treat, often involving several medications with significant side effects and modest benefits," said Boehnke. "Further, many alternative therapies, like acupuncture and massage, are not covered by insurance."

CBD is one of the chemical compounds found in cannabis, but it doesn’t have the same intoxicating effect as tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana.  Some cannabis products contain a combination of THC and CBD, while others just have CBD.

Survey participants who used CBD products containing THC were more likely to report symptom relief and to use them as substitutes for pain medication. This suggests that THC may enhance the therapeutic benefits of CBD.

A recent Israeli study found that people with fibromyalgia who took daily doses of cannabis oil rich in THC had significantly less pain and fatigue.

Another recent study in Israel found that cannabis products – both with and without THC – reduced pain and depression in fibromyalgia patients. Like the findings of the Michigan study, about one out of five patients either stopped taking or reduced their use of opioids and benzodiazepines.

"People are using CBD, substituting it for medication and doing so saying it’s less harmful and more effective,” said Boehnke. “If people can find the same relief without THC's side effects, CBD may represent a useful as a harm reduction strategy."

The Michigan Medicine study was recently published in The Journal of Pain.