FDA Warns Companies Selling CBD and Delta-8 THC Products

By Pat Anson, PNN Editor

When Congress passed the 2018 Farm Bill and legalized hemp under federal law, the goal was to make it possible for U.S. farmers to grow hemp again as a cash crop for making everything from clothing and fuel to shampoo and horse feed. “Rope, not dope,” was the slogan used by the bill’s supporters, who pointed out that hemp contains less than 0.3% tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana.  

No one could possibly get high on hemp, could they?

It didn’t take long for the cannabis industry to figure out how. Many companies now make cannabidiol (CBD) products from hemp and tweak their chemical composition just enough to produce the euphoria that some consumers seek. A recent study by CBD Oracle found that some hemp-based edibles have 360% more THC than those sold in cannabis dispensaries. Over half the edibles they tested were mislabeled.

The Food and Drug Administration has been slow to regulate CBD products or confront mislabeling, but today the agency finally took action by sending the first warning letters to cannabis companies for selling products containing delta-8 tetrahydrocannabinol (delta-8 THC), which the agency considers an unapproved drug.

Delta-8 THC is one of over 100 cannabinoids found in marijuana, but is not present in significant amounts in hemp. However, some companies have found ways to concentrate delta-8 THC from hemp-derived CBD to give users a mild psychoactive and intoxicating effect.

Edibles containing delta-8-THC are being sold as candy, cookies, breakfast cereal, chocolate, gummies, tinctures and beverages. Because they are made from hemp, they can legally be purchased without an ID or marijuana prescription – even in states where medical or recreational marijuana is illegal.

"The FDA is very concerned about the growing popularity of delta-8 THC products being sold online and in stores nationwide. These products often include claims that they treat or alleviate the side effects related to a wide variety of diseases or medical disorders, such as cancer, multiple sclerosis, chronic pain, nausea and anxiety," FDA Principal Deputy Commissioner Janet Woodcock, MD, said in a statement. "It is extremely troubling that some of the food products are packaged and labeled in ways that may appeal to children.”

In the last two years, the FDA says it has received 104 reports of adverse events involving delta-8 THC, most of them involving edibles. National poison control centers have reported over 2,300 cases involving delta-8 THC products, including one death involving a child.

The FDA has previously warned companies about making unsubstantiated medical claims about CBD products, but these are the first warnings to target delta-8 THC specifically. The five companies that received the letters -- ATLRx, BioMD Plus, Delta 8 Hemp, Kingdom Harvest and M Six Labs make only vague medical claims on their websites, telling consumers about “dosing Delta-8 THC for optimal effects” and how their products help “alleviate stress, anxiety, and uneasiness.”

Curiously, some of the companies also sell CBD products made with delta-9 THC – a more potent cannabinoid that can be derived from hemp – which the FDA ignored in its warning, even though delta-9 is also an unapproved drug. The agency’s warning letters also say nothing about mislabeling. Simply having delta-8 in a product — at any dose — is considered illegal.

The cannabis industry is still coming to terms with all of this and how hemp legalization is having unintended consequences.

“We honestly never thought intoxicating products would be produced from hemp when we were advocating for legalization,” Erica Stark of the National Hemp Association told CBD Oracle. “Now the FDA needs to figure out how to regulate the industry.”

Will Congress amend federal law to protect consumers and regulate how hemp is utilized? A bill under consideration would raise THC levels even higher.

Under the proposed Hemp Advancement Act of 2022, which is supported by the hemp industry, the legal THC threshold for hemp products would be raised from 0.3 percent to 1 percent.  Participation in the hemp industry would also be expanded to include people with prior drug convictions.

Cannabis Legalization Reduced Rx Drug Use for Several Conditions, Not Just Pain

By Pat Anson, PNN Editor

Cannabis products are often touted for their pain relieving properties and some studies have shown that medical marijuana can even help patients reduce their use of opioids.

But a large new study by researchers at Cornell University found that legalization of recreational marijuana significantly reduced demand for a broad range of prescription drugs used to treat depression, anxiety, seizures and other health conditions.

The study, published in the journal Health Economics, looked at prescription data for Medicaid patients in all 50 states from 2011 to 2019, focusing on 11 states where the recreational use of cannabis was legalized: Arizona, Alaska, California, Colorado, Maine, Massachusetts, Michigan, Nevada, Oregon, Vermont and Washington.

Researchers found significant reductions in Medicaid prescribing rates for pain and five other condition-specific drug classes after the first year of legalization:

• -12.2% Anxiety

• -11.1% Depression

• -10.8% Sleep  

• -10.7% Psychosis

•  -9.5% Seizures

•    -8% Pain

Prescribing rates for the six conditions declined even more in the second and third years after recreational cannabis was legalized.

"These results have important implications," wrote lead author Shyam Raman, a doctoral student in the Cornell Jeb E. Brooks School of Public Policy. "The reductions in drug utilization that we find could lead to significant cost savings for state Medicaid programs. The results also indicate a potential harm reduction opportunity, as pharmaceutical drugs often come with dangerous side effects or – as with opioids – potential for misuse.”

Raman and his colleagues did not see a measurable change in the prescribing of drugs used to treat nausea, spasticity or glaucoma. They also note that their study did not look at the health of patients who stopped or reduced their use of prescription drugs, or at the long-term effects of substituting cannabis for pharmaceuticals.

A small study at Harvard Medical School recently found that chronic pain patients reported significant improvements in their pain, sleep, mood, anxiety and quality of life after six months of cannabis therapy.

Recreational cannabis is now legal in 18 states and Washington, DC, while medical marijuana is legal in 37 states and Washington, DC. Cannabis has become so popular — and accessible — that a recent Harris poll found that twice as many Americans are using cannabis or cannabidiol (CBD) to manage their pain than opioids.

While the findings are intriguing, the small number of patients involved in most cannabis studies makes it hard to draw firm conclusions. In 2021, two professional pain societies – the International Association for the Study of Pain (IASP) and the Australian and New Zealand College of Anaesthetists -- released policy statements saying they could not endorse the use of cannabis for pain because there are no large, high-quality clinical trials of cannabis as an analgesic.

Study Finds Cannabis Oil Effective in 9 out of 10 Pain Patients

By Pat Anson, PNN Editor

Medical cannabis improved symptoms in 9 out of 10 chronic pain patients taking oral formulations of cannabidiol (CBD) and tetrahydrocannabinol (THC), according to a large new study in Colombia.

The observational study, the largest of its kind in Latin America, is the first clinical peer-reviewed evidence on the effectiveness and safety of cannabis products made by Khiron Life Sciences. Over 2,100 patients with a variety of chronic pain conditions self-reported their symptoms after taking CBD and THC oil-based formulations at a Khiron clinic in Bogota.

The findings are published in the peer-reviewed journal Frontiers in Pain Research.

"We believe these findings to be generalizable across patient populations, considering that our results are extremely well-aligned with those reported by researchers working with similar clinical populations in nations with long-standing medicinal cannabis access programs, such as Israel and Canada," lead author Guillermo Moreno-Sanz, Global Scientific Director of Khiron Life Sciences, said in a press release.

While most previous studies only looked at the short-term effects of cannabis ingested through a variety of different methods, this study focused on the safety and efficacy of cannabis oils for up to 26 weeks. Most participants were female, with an average age of 59 years.

Patients received cannabis oils composed primarily of CBD (30mg CBD/2mg THC) or a more balanced formulation (14mg CBD/12mg THC). 

Key findings in the study include:

• 92.5% of patients reported some degree of improvement in their chronic pain.

• 75% reported moderate or robust reduction in chronic pain

• 72% reported no adverse side effects

The degree of improvement was similar between both formulations, although males reported less effectiveness in the first 4 weeks of treatment.

Most side effects were mild, such as somnolence (13%), dizziness (8%) and dry mouth (4%), and faded away after 12 weeks of treatment. No serious adverse events requiring hospitalization or medical intervention were reported.

"This study, based on Khiron's medical products, is critical to reassure physicians and health insurance providers of the efficacy of medicinal cannabis to treat chronic pain. The global impact and economic burden of chronic pain in our society, mounting medical evidence will increase access to cannabinoid-based medicines worldwide." says Alvaro Torres, Khiron CEO and Director.

Khiron Life Sciences is a medical cannabis company based in Colombia. Its products are sold in Colombia, Peru, Germany, UK and Brazil, and will soon be available in Mexico.

Recent studies have also found cannabis oil effective in treating fibromyalgia and migraine.

Can Opioids Be Safely Used with Cannabis?

By Pat Anson, PNN Editor

Many doctors who prescribe opioids to pain patients tell them not to mix opioids with cannabis – fearing a combination of the two could raise the risk of addiction and overdose. Some doctors will stop prescribing opioids to patients or even discharge them if cannabis is detected in their drug tests.

But a new animal study suggests that cannabidiol (CBD) and tetrahydrocannabinol (THC) – the active ingredients in marijuana – may actually be safe to use with opioids and could be an effective way to lower opioid doses while still providing pain relief. 

“There is intense interest in using medical marijuana in patients with chronic pain because compounds in marijuana like CBD and THC may produce pain relief themselves or enhance the pain-relieving effects of opioids,” said Lawrence Carey, PhD, a postdoctoral fellow at the University of Texas Health Science Center, San Antonio. “This means people could potentially use lower doses of opioids and still get relief from pain. Taking less pain medication could also lead to a lowered risk of addiction or physical dependence to opioids.”

Carey and his colleagues tested their theory by giving rhesus monkeys dependent on opioids various doses of CBD and THC, either alone or together. The monkeys were then given opportunities to press levers that either gave them a food reward or an injection of fentanyl, a potent synthetic opioid.

Their findings, presented this week at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics, showed that CBD and THC did not increase or decrease the number of times the primates selected fentanyl over food. This suggests that cannabis does not enhance the rewarding effects of opioids or raise the risk of addiction, at least for rhesus monkeys.

“Giving the animals the opportunity to choose between a drug injection and a food reward helped us to somewhat replicate choices a human drug user may face, such as whether to spend money on drugs or food,” Carey said in a press release. “Having the option of responding for food is also useful for studying drugs like THC that produce sedative effects. It helps demonstrate the animal is reallocating behavior from drug to food choice instead of simply shutting down response for a drug due to sedation.”

Carey says more studies on humans are needed to determine whether THC and CBD are safe to use with opioids, and if they work well together.

A 2020 study of patients prescribed opioids for chronic low back pain found that half were able to stop using opioids after starting cannabis therapy, but it took an average of six years to do so. About 15% reduced their use of opioids and the remainder either kept taking the same amount or increased their opioid use.

Carey is now conducting animal studies to assess whether CBD and THC can decrease symptoms of opioid withdrawal. 

“A big reason why people continue to take opioids after they become addicted is the appearance of withdrawal symptoms,” said Carey. “We are using what we learned from this study to determine whether these doses — which didn’t alter choice for food or drug rewards — may help relieve opioid withdrawal or decrease relapse and drug seeking behavior following periods of abstinence.”  

Medical Cannabis Is Losing Credibility

By Roger Chriss, PNN Columnist

As more and more states legalize medical cannabis for chronic pain, anxiety, seizure disorders and other common medical conditions, the question of efficacy becomes increasingly important. Recent studies show a lack of efficacy, but so far states are not modifying their list of approved conditions for medical cannabis.

Many states approved cannabis for medical conditions without good evidence. California legalized medical marijuana in 1996, yet nearly three decades later the Medical Board of California is still advising physicians that “there is a lack of evidence for the efficacy of cannabis in treating certain medical conditions.”

We not only still lack evidence, but new research suggests that cannabis doesn’t help and may actually be harmful:

• A small randomized trial in Boston found no significant improvement in pain, anxiety or depression in people given medical marijuana cards, but a higher risk of developing cannabis use disorder.

• A matched cohort study in Hawaii on people 50 or older saw a “significantly greater risk of coronary heart disease, chronic non-cancer pain, stroke, myocardial infarction, cyclic vomiting, and injuries” in people using cannabis compared to non-users.

• An observational study in New York of 29 people with epilepsy given two formulations of cannabidiol (CBD) and tetrahydrocannabinol (THC) concluded that “we found no evidence of efficacy… in treating epilepsy, sleep, or behavior in our population.”

Recent reviews of past studies are similarly disappointing.

• A review of 16 studies of CBD for mental health disorders found that “there is currently not enough high-quality evidence to suggest the clinical use of CBD for any psychiatric disorder.”

• A systematic review of 28 studies on medical marijuana for multiple sclerosis concluded that “the magnitudes of effects on short-term neurological outcomes in MS patients are either small, limited, or moderate.”

Lack of Efficacy

The 2017 National Academies report on cannabis noted the need for more research. Since then, over 6,400 studies have appeared on PubMed on medical cannabis specifically, and a total of 12,100 studies on cannabis in general. More studies are forthcoming, including 460 clinical trials of cannabis that are active or recruiting.

The result so far is a growing body of high-quality studies and clinical trials published in major journals showing a lack of efficacy and a risk of poor outcomes for conditions that cannabis is state-approved for.

Ordinarily, states follow the laws and regulations of the Food and Drug Administration, recommendations from medical societies, and research findings and other sources of major reviews. With almost any other substance with such a weak track record, there would have been a reassessment by now. But not with cannabis.

California still approves medical cannabis for glaucoma, even though the American Academy of Ophthalmology is against it due to lack of efficacy. California is not alone. So far, no state has removed any condition from its approved list for medical cannabis use.

However, the conditions of using cannabis are changing. Some states now require patients in pain management programs to have their urine tested for cannabinoids. Many medication management agreements – known as “pain contracts” – also expressly forbid cannabis use even if it has been legalized in that state. Some medical specialties tell patients to simply avoid cannabis because of risks from drug interactions and contraindications.

Although cannabis may be safer than some prescription drugs, that won’t matter if it has no demonstrable benefit. Cannabis is losing credibility as a therapeutic as studies show poor outcomes for diagnoses that states approve cannabis for.

Holding cannabis to the same standards as other therapeutics would increase confidence in cannabis where it is shown to be beneficial. It will also help improve patient outcomes. As it stands now, however, medical cannabis is starting to look more like medicinal alcohol during Prohibition than a credible therapeutic for 21st-century medicine.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research. 

New CBD Drug Developed for Postoperative Pain

By Pat Anson, PNN Editor

An investigational drug containing a fast-acting formula of cannabidiol (CBD) reduced postoperative pain in patients after shoulder surgery, according to small new study.

Patients who took ORAVEXX tablets after minimally invasive rotator cuff surgery had an average of 23 percent less pain after the first day of surgery than those taking a placebo, according to researchers at NYU Langone Health. The tablets are designed to quickly dissolve in the mouth and the CBD absorbed into the bloodstream in less than 3 seconds.

“There is an urgent need for viable alternatives for pain management, and our study presents this form of CBD as a promising tool after arthroscopic rotator cuff repair,” says lead investigator Michael Alaia, MD, associate professor in the Department of Orthopedic Surgery at NYU Langone Health.

“It could be a new, inexpensive approach for delivering pain relief, and without the side effects of anti-inflammatory drugs like NSAIDs and addiction risks linked to opiates. Additionally, CBD has the benefit of pain relief without the psychotropic effects associated with THC or marijuana.”

There are a few caveats about the study. First, only 99 patients were enrolled in this early-stage Phase 1/2 trial. They were divided into two groups: one group took 50 mg of CBD in ORAVEXX tablets three times a day for 14 days, while the other group received a placebo or 25 mg of CBD during the study period.

Importantly, patients in both groups were also prescribed opioids, a low dose of Percocet, and told to wean themselves off the medication as soon as possible.

There were no major side effects reported by either group, but the group receiving 50 mg of CBD reported less pain and greater satisfaction in their pain control.

ORAVEXX is manufactured by Orcosa, which has developed a proprietary drug delivery system called the RITe Platform. The company says it buccal tablets dissolve so quickly in the mouth that fewer active ingredients are needed for a medication to work.

In addition to postoperative pain, the company is also planning studies to evaluate ORAVEXX as a treatment for acute and chronic pain, osteoarthritis pain and inflammation. While the initial results are promising, researchers say it could be years before ORAVEXX is available.

“Our study is examining a well-designed, carefully scrutinized product under an investigational new drug application sanctioned by the FDA. This is currently still experimental medicine and is not yet available for prescription,” said Alaia, who presented the initial findings this week at the annual meeting of the American Academy of Orthopaedic Surgeons.

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.