More Canadians Using Cannabis for Pain Relief

By Pat Anson, PNN Editor

Chronic pain sufferers in the United States and Canada are increasingly turning to cannabis for pain relief. The latest evidence of that is a large survey of people in pain in Quebec, Canada.

Of the 1,344 participants who answered questions about their cannabis use, nearly a third (30.1%) said they used cannabis for pain management, far more than those who used it for other health conditions (9.1%) or for recreational purposes (12.7%).

The online survey was conducted in 2019, a few months after recreational cannabis was legalized in Canada in October, 2018.  Prior to full legalization, cannabis use by Canadians living with chronic pain was estimated at 10% or less.

“Based on studies conducted before the legalization of recreational cannabis, the prevalence of cannabis use estimated in the present study indicates a threefold increase in reported usage,” researchers reported. “Because people living with CP (chronic pain) have reported using even more cannabis during the first wave of the COVID-19 pandemic, it seems reasonable to expect the prevalence to be even higher today. Our results suggest that cannabis is a common treatment reported by people living with CP and underscore the importance of rapidly generating more evidence on the safety and efficacy of cannabis.”

The survey findings, recently published in the Canadian Journal of Pain, show that pain sufferers under the age of 26 were most likely to use cannabis (36.5%), while those aged 74 and older were least likely (8.8%). Three out of four respondents reported living with pain for at least 5 years. Over two-thirds (67.7%) said they had moderate to severe pain.

A 2021 Harris Poll found that twice as many Americans are using cannabis or CBD to manage their pain than opioid medication. Over-the-counter pain relievers were used by over half (53%) of those surveyed, followed by cannabis products (16%), non-opioid pain relievers (11%) and opioids (8%). Two-thirds of Americans with chronic pain (66%) said they had changed their pain management since the pandemic began, and were using more OTC pain relievers and cannabis products.

Neither the Harris or Canadian surveys specifically asked respondents if they were using cannabis for pain relief because opioids were harder to obtain. Opioid prescribing in the U.S. and Canada has declined significantly in the past decade due to more restrictive medical guidelines and fears about abuse.

Patients With Epilepsy Navigate Murky CBD Market

By Eric Berger, Kaiser Health News

In 2013, Tonya Taylor was suicidal because her epileptic seizures persisted despite taking a long list of medications.

Then a fellow patient at a Denver neurologist’s office mentioned something that gave Taylor hope: a CBD oil called Charlotte’s Web. The person told her the oil helped people with uncontrolled epilepsy. However, the doctor would discuss it only “off the record” because CBD was illegal under federal law, and he worried about his hospital losing funding, Taylor said.

The federal government has since legalized CBD, and it has become a multibillion-dollar industry. The FDA also has approved one cannabis-derived prescription drug, Epidiolex, for three rare seizure disorders.

But not much has changed for people with other forms of epilepsy like Taylor who want advice from their doctors about CBD. Dr. Joseph Sirven, a Florida neurologist who specializes in epilepsy, said all of his patients now ask about it. Despite the buzz around it, he and other physicians say they are reluctant to advise patients on over-the-counter CBD because they don’t know what’s in the bottles.

The FDA does little to regulate CBD, so trade groups admit that the marketplace includes potentially harmful products and that quality varies widely. They say pending bipartisan federal legislation would protect those who use CBD. But some consumer advocacy groups say the bills would have the opposite effect.

Caught in the middle are Taylor and other patients desperate to stop losing consciousness and having convulsions, among other symptoms of epilepsy. They must navigate the sometimes-murky CBD market without the benefit of regulations, guidance from doctors, or coverage from health insurers. In short, they are “at the mercy and the trust of the grower,” said Sirven, who practices at the Mayo Clinic in Jacksonville.

While the CBD industry is new territory for the FDA, people have used cannabis to treat epilepsy for centuries, according to a report co-authored by Sirven in the journal Epilepsy & Behavior.

More than 180 years ago, an Irish physician administered drops from a hemp tincture to an infant experiencing severe convulsions. “The child is now in the enjoyment of robust health, and has regained her natural plump and happy appearance,” Dr. William Brooke O’Shaughnessy wrote at the time.

Charlotte’s Web

Much of the recent interest in CBD stemmed from the 2013 CNN documentary “Weed,” which featured Charlotte Figi, then 5, who had hundreds of seizures each week. With the use of CBD oil, her seizures suddenly stopped, CNN reported. After that, hundreds of families with children like Charlotte migrated to Colorado, which had legalized marijuana in 2012.

Then in 2018, the federal government removed hemp from the controlled substances list, which allowed companies to ship CBD across state lines and meant families no longer needed to relocate.

The FDA still prohibits companies from marketing CBD products as dietary supplements and making claims about their benefits for conditions such as epilepsy.

“The FDA has really done little to protect consumers from an unregulated marketplace that they have created.”

— Megan Olsen, Council for Responsible Nutrition

The agency is gathering “research, data and other safety and public health input to inform our approach and to address consumer access in a way that protects public health and maintains incentives for cannabis drug development through established regulatory pathways,” Dr. Janet Woodcock, then the FDA’s acting commissioner, said in 2021, according to a dietary supplements trade group.

“The FDA has really done little to protect consumers from an unregulated marketplace that they have created,” said Megan Olsen, general counsel for the Council for Responsible Nutrition, a different dietary supplements trade group.

A recent study in Epilepsy & Behavior on 11 oils found that three contained less CBD than claimed, while four contained more. Charlotte’s Web contained 28% more CBD than advertised, according to the report. The study also pointed out that the problems “mirror concerns” raised for generic anti-seizure medications, which the FDA does regulate.

“I’m not anti-CBD,” said Barry Gidal, a professor of pharmacy and neurology at the University of Wisconsin-Madison who co-authored the study and worked as a consultant for the Epidiolex manufacturer. “There needs to be oversight so that patients know what they are getting.”

Some states, such as Michigan, have cannabis regulatory agencies. As such, Dr. Gregory Barkley, a neurologist at Henry Ford Hospital in Detroit, thinks that when a person shops at one of the state’s dispensaries, “you have a pretty good idea of what you’re getting.” Barkley regularly reviews his patients’ CBD products and discusses how many milligrams they take to help control their epilepsy.

But Barkley said CBD has inherent variability because it comes from a plant.

“It’s no different than saying, ‘I’m going to treat you with a Honeycrisp apple for an ailment.’ Every apple is a little bit different,” said Barkley. “The lack of standardization makes it difficult.”

About five years ago, Trina Ferringo of Turnersville, New Jersey, asked a pediatric neurologist about giving CBD to her teenage son, Luke, because his prescription drugs were causing severe side effects yet not preventing his epileptic seizures. The doctor was “adamantly opposed to it” because of the lack of FDA oversight and concerns it might contain THC, the chemical in marijuana that produces a high, Ferringo recalled.

Instead, in 2018, the doctor prescribed Epidiolex. Luke went from having several seizures each week to a couple per month. Ferringo is pleased with the outcome but now often fights with her insurance company because Epidiolex, which has a list price of $32,500 per year, isn’t approved for her son’s form of epilepsy.

Charlotte’s Web typically costs between $100 and $400 each month, depending on how much someone takes. Unlike Epidiolex, insurance never covers it.

Beyond the cost difference, it’s unclear whether a highly purified CBD product such as Epidiolex is more effective than products like Charlotte’s Web that contain CBD and other plant compounds, creating what scientists describe as a beneficial “entourage effect.”

A 2017 review of CBD studies in the journal Frontiers in Neurology, authored by scientists in the cannabis industry, found 71% of patients with treatment-resistant epilepsy reported a reduction in seizures after taking the CBD-rich products, but among patients taking purified CBD, the share was only 46%.

Patients taking CBD-rich products rather than purified CBD also reported taking lower daily doses and experiencing fewer side effects.

“Every cannabinoid when individually tested has a degree of anticonvulsant properties so that if you give a blend of various cannabinoids, they will have some additive effect,” Barkley said.

Changing CBD Regulations

Bipartisan legislation pending in Congress would designate CBD as a dietary supplement or food. The Senate version would allow the federal government to “take additional enforcement actions” against such products.

Jonathan Miller, general counsel to the U.S. Hemp Roundtable, a coalition of hemp companies, said the legislation would protect consumers and allow CBD manufacturers to sell their products in stores as dietary supplements.

However, Jensen Jose, counsel for the Center for Science in the Public Interest, said such legislation would actually make consumers less safe. The FDA does not have the authority to review dietary supplements for safety and effectiveness before they are marketed and does not routinely analyze their ingredients.

“If a CBD company right now is doing something questionable or potentially unsafe, the FDA can easily remove the product simply for being illegally marketed as a drug,” said Jose. If the legislation passes, he said, the FDA could not do that.

Instead, Jose said, Congress should provide the FDA with more authority to regulate CBD and dietary supplements and more funding to hire inspectors.

The FDA does not comment on pending legislation, spokesperson Courtney Rhodes said.

Patients like Taylor, the Colorado woman with epilepsy, aren’t waiting for the federal government. After the doctor’s visit, she borrowed money from family members and purchased a bottle of Charlotte’s Web.

“The effects were night and day,” she said. “I was able to get out of bed.”

She befriended a grower and spends about $50 per month on CBD powder, gummies, and oil. She now takes only one prescription medication for seizures rather than four. She has about one seizure per month, which means she can’t drive. Her medical providers still don’t seem open to discussing CBD, she said, but that doesn’t bother her much.

“After being on it for this many years and seeing the evidence — the 180-degree turnaround that my life made — it’s a choice I’m going to make whether they are with it or they are against it,” she said. “It’s working for me.”

Kaiser Health News is a national newsroom that produces in-depth journalism about health issues.

Nearly Half of CBD Oils Are Mislabeled

By Pat Anson, PNN Editor

CBD oils derived from hemp are increasingly being used to relieve painful conditions. Studies have found the oils effective in treating migraines and fibromylagia, and recent research found that a proprietary blend of CBD oil helped relieve symptoms in 9 out of 10 people suffering from chronic pain.

But a new study at the University of Kentucky College of Medicine found that nearly half of the CBD oil products tested in a lab were mislabeled. Of the 80 CBD oils purchased online or in retail stores, only 43 had concentrations of cannabidiols that were within 10% of their label claims – an accuracy rate of just 54 percent.

One oil had a CBD concentration that was 159% higher than its label indicated. Another oil had only 17% of the CBD it was supposed to have.

“As most consumers are using CBD products as therapeutic treatments for some types of medical condition, the dosing is important when considering the potential for CBD accumulation, elevation of liver enzymes, and drug-drug interactions,” lead author Erin Johnson reported in the Journal of Cannabis Research.  

“The findings reported here emphasize the continued need for clear and consistent regulation from federal and state agencies to ensure label accuracy of CBD products and subsequent enforcement. These results also indicate the need for continued development of good manufacturing practices and testing standards.”

In a separate analysis of the same CBD oils, Johnson and her colleagues found that most contained trace amounts of THC (tetrahydrocannabinol), the psychoactive substance in cannabis. Five of the 21 CBD oils that were labeled "THC Free" contained detectable levels of THC.

"THC is not allowed at the Olympics. It's not allowed in many sports organizations. But athletes use CBD because it helps them recover, and it helps them with different facets of their training," co-author Shanna Babalonis said in a press release. "So I think that one of the key takeaways from this work is to say that the public needs to question whether there's THC in their CBD products."

The two studies are certainly not the first to find that cannabis products are often mislabeled. They point to a continuing problem since passage of the 2018 Farm Bill, which legalized hemp under federal law. Although hemp contains only trace amounts of THC, cannabis companies have found ways to tweak its chemical composition to produce concentrated levels of delta-8 THC, which has a mild psychoactive and intoxicating effect.

The FDA considers delta-8 THC to be an unapproved drug, but because it comes from hemp – a legal substance – its regulatory status is unclear. Recently, the FDA sent the first warning letters to five cannabis companies, not for mislabeling, but for making unsubstantiated medical claims about delta-8 THC.  

Until the FDA or individual states confront the widespread mislabeling of CBD products, industry insiders say it’s likely to continue. 

“The mislabeling of Delta-8 products is not surprising but is a result of poor quality controls that are present through the category. Delta 8 can be unsafe for people to use, especially if it not labeled. This is due to the psychoactive component of Delta 8,” said John McDonagh, CEO of CBD producer NextEvo Naturals.  

“Some states have started to regulate Delta 8 to take it off the market. The FDA is limited as it doesn’t have sufficient enforcement resources, so the best solution for now is for states to take action.”

Low-Dose Cannabis Inhaler Effective in Treating Chronic Pain

By Pat Anson, PNN Editor

Low-doses of medical cannabis delivered through an inhaler significantly reduced pain in patients with neuropathy, back pain and other chronic pain conditions, according to a new study.

Researchers assessed the efficacy of vaporized cannabis in 138 pain patients using the Syqe Inhaler, a pocket-sized device that delivers microdoses of aerosolized cannabis. The study was funded and conducted by Syqe Medical, a medical technology company in Israel that makes the inhaler.

Unlike smoking or traditional vaping, the Syqe inhaler heats the cannabis to a temperature below combustion and uses airflow controls to deliver precise doses of cannabis to the patient's lungs in less than 2 seconds. The mean dose in the study was 1.5 mg of aerosolized delta-9-THC, a fraction of what a typical cannabis user would get from a joint or vaporizer.

Participants in the study used the inhaler up to several times a day, depending on need, and were followed for up to a year.

The study findings, published in the journal Pain Reports, show that pain levels fell from an average of 7.3 (on a zero to 10 pain scale) to 5.5 after 120 days – a reduction of nearly 23 percent. For patients in severe pain, pain levels dropped over 28 percent.

Most participants also reported significant improvement in their quality of life, with 92% saying their lives were “better” or “much better.”  

Of the 43 patients who were using opioid pain medication at the start of the study, 58% reported using lower doses after initiating treatment with the inhaler.

Adverse events, such as dizziness and headache, were minor and usually lasted only a few minutes. About 17% of patients reported no decrease in pain intensity and 7% reported more pain.

SYQE MEDICAL IMAGE

“Medical cannabis treatment with the Syqe Inhaler demonstrated overall long-term pain reduction, quality of life improvement, and opioid-sparing effect in a cohort of patients with chronic pain, using just a fraction of the amount of MC (medical cannabis) compared with other modes of delivery by inhalation,” researchers reported.

“These outcomes were accompanied by a lower rate of AEs (adverse events) and almost no AE reports during a long-term steady-state follow-up. Additional follow-up in a larger population is warranted to corroborate our findings.”

The Syqe Inhaler is currently only available in Israel and Australia. The company said in an email that it plans to launch the device in Canada and New Zealand in the coming months. No timetable was offered on its availability in the United States.

“We believe it is our responsibility to reduce the pain and suffering of as many patients as possible in the fastest possible way, and we are determined to make medical cannabis treatment a standard of care utilizing advanced technologies,” said Sharon Cohen of Syqe’s Customer Experience Team.

Critics Challenge Study That Found Little Evidence to Support Use of Cannabis

By Pat Anson, PNN Editor

Medical marijuana advocates are challenging the findings of a new study that found little clinical evidence to support the use of cannabis in treating chronic pain.

“The findings appear out of step with the real-world experience of millions of patients who have come to rely on cannabis for pain management,” said Paul Armentano, Deputy Director of NORML.

The federally-funded systematic review – essentially a study of studies – was conducted by researchers at Oregon Health & Science University (OHSU), who analyzed over 3,000 cannabis studies. They could find only 25 studies that met their criteria for review. Only placebo controlled clinical trials or observational studies lasting at least four weeks were included. The rest were deemed to be poor quality or flawed in some way.

“In general, the limited amount of evidence surprised all of us,” said lead author Marian McDonagh, PharmD, professor of medical informatics and clinical epidemiology in the OHSU School of Medicine. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.”

‘Biased Findings’

Most of the 25 cannabis studies that met OHSU’s criteria for review were considered biased in some way — 30% of the clinical trials were considered to have “high risk of bias” and half had “medium risk of bias.”  Most of the observational studies were also considered biased.

Despite the limited evidence, the OHSU research team came to some sweeping conclusions. Their study, published in the Annals of Internal Medicine, found no evidence to support the use of cannabidiol (CBD) or cannabis leaves, buds and flowers in treating pain. Only synthetic cannabis products rich in tetrahydrocannabinol (THC) were found to provide short-term relief from neuropathic pain.

Curiously, the OHSU researchers included in their review studies that evaluated the effectiveness of dronabinol and nabilone, two cannabis-based medications that are only FDA-approved to treat nausea, vomiting and weight loss. They are not formulated to treat chronic pain. Similarly, another study looked at the effectiveness of a cannabis extract in treating muscle stiffness (spasticity) caused by multiple sclerosis.

“It would appear that authors' relatively narrow focus and emphasis on both synthetic cannabis formulations (which historically have not demonstrated similar efficacy to whole-plant cannabis) as well as upon extracts that were initially designed to target medical ailments other than pain management may have biased these findings,” Armentano said in an email to PNN. 

“Numerous controlled trials involving whole-plant cannabis and reviews of said trials have determined that there exists substantial evidence that cannabis is safe and effective in pain management, particularly for neuropathy.” 

Armentano said nearly two-thirds of people enrolled in state-run medical cannabis programs registered for the treatment of chronic pain.

“Controlled studies have further indicated that cannabinoids can act synergistically with opioids, resulting in patients requiring lower doses to achieve relief. This is likely why we now have dozens of studies finding that pain patients taking opioids who initiate medical cannabis use frequently reduce or eliminate their opioid use over time,” Armentanohe said.

More Studies Needed

The OHSU researchers say more high-quality studies are needed on the safety and efficacy of cannabis products, which are largely unregulated by the FDA.

“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” co-author Roger Chou, MD, director of OHSU’s Pacific Northwest Evidence-based Practice Center said in a press release. “That makes it tough for patients and clinicians, since the evidence for one cannabis-based product may not be the same for another.”

Chou is a controversial figure in the pain community. A prolific researcher and frequent critic of opioid prescribing, Chou co-authored the CDC’s controversial 2016 opioid guideline. Although he has acknowledged conflicts of interest, Chou remains as one of the co-authors of a revised CDC guideline, which is expected to be released later this year.

The cannabis findings are similar to those in another OHSU review, which found no clinical evidence to support the use of kratom, an herbal supplement used by millions of Americans to relieve pain, anxiety, depression and other medical conditions.     

The studies on cannabis, kratom and other plant-based treatments are potentially worth up to $1.4 million for OHSU, a public research university that the federal government often turns to for medical research. According to the website GovTribe, in the last five years OHSU has been awarded nearly $2 billion in federal research grants, much of it coming from the Agency for Healthcare Research and Quality (AHRQ).

Medical Cannabis Improves Symptoms in Cancer Patients

By Pat Anson, PNN Editor

Medical cannabis improved pain and other symptoms in patients undergoing cancer treatment, while significantly reducing their use of opioids and other analgesics, according to a new study by Israeli researchers.

Over 300 cancer patients participated in the 6-month study, including many who were seriously ill. Breast, colon, lung and ovarian cancers were the most common diagnoses, with about half the patients receiving chemotherapy (55%) or diagnosed with advanced stage IV cancer (48%).

“Traditionally, cancer-related pain is mainly treated by opioid analgesics, but most oncologists perceive opioid treatment as hazardous, so alternative therapies are required,” said lead author David Meiri, PhD, an assistant professor at the Technion-Israel Institute of Technology in Haifa.

“Our study is the first to assess the possible benefits of medical cannabis for cancer-related pain in oncology patients; gathering information from the start of treatment, and with repeated follow-ups for an extended period of time, to get a thorough analysis of its effectiveness.”

Patients ingested cannabis that was rich in tetrahydrocannabinol (THC) through oil extracts, smoking or a combination of the two. For many, it was their first time using cannabis.

Most patients (60%) reported a positive effect from cannabis treatment, with significant improvement in their anxiety, depression, sleep, quality of life and pain catastrophizing. Most reported a small improvement in pain intensity and 20% said there was no improvement in their pain levels.

There was, however, a significant change in the use of analgesics. About 40 percent of patients who were taking pain medication of some kind (opioids, NSAIDs, anticonvulsants or antidepressants) stopped taking the drugs while using cannabis.

“We encountered numerous cancer patients who asked us whether medical cannabis treatment can benefit their health,” said co-author Gil Bar-Sela, MD, an associate professor at the Ha'Emek Medical Center Afula. “Our initial review of existing research revealed that actually not much was known regarding its effectiveness, particularly for the treatment of cancer-related pain, and of what was known, most findings were inconclusive.”

Notably, about one in every five participants died during the course of the study, which researchers attributed to their poor health and advanced cancer. Many of the patients also lost weight.

“Medical cannabis has been suggested as a possible remedy for appetite loss, however, most patients in this study still lost weight. As a substantial portion were diagnosed with progressive cancer, a weight decline is expected with disease progression,” said Meiri. “Interestingly, we found that sexual function improved for most men but worsened for most women.”

Overall, researchers say cannabis treatment provided “mild to modest” improvement in cancer patients, with only minor side effects. Their findings were published in the journal Frontiers in Pain Research.

FDA Head Wants New Regulations for Kratom and CBD

By Pat Anson, PNN Editor

The head of the Food and Drug Administration says his agency will need new authority from Congress to regulate both kratom and cannabidiol (CBD), two natural substances used by millions of Americans to self-treat their pain and other medical conditions.

FDA Commissioner Dr. Robert Califf testified on Thursday before a House Appropriations subcommittee, where he was asked why the agency was slow in developing new regulations for CBD and why it remained opposed to the use of kratom. Califf said new regulatory pathways were needed for both substances because they fall between the cracks of existing law that gives the FDA broad authority to regulate food and drugs.

“I don’t think the current authority we have, on the food side and the drug side, necessarily gives us what we need to have to get the right pathway to move us forward. We’re going to have to come up with something new. I’m very committed to doing that,” said Califf.

Califf was recently confirmed by the U.S. Senate as FDA commissioner, a job he previously held under President Obama. He noted that little progress had been made at the FDA in regulating CBD and other cannabis products since he left the agency.

“You know, when you come six years later to the job you had before and nothing has really changed, that’s telling you that you can’t just keep trying to do the same thing over and over,” said Califf.

Some of the difficulty in regulating CBD comes from passage of the 2018 farm bill, which legalized hemp under federal law. At the time, it was believed that hemp had little or no psychoactive properties and would be relatively harmless. However, as PNN has reported,  some cannabis companies have found ways to concentrate delta-8 tetrahydrocannabinol (delta-8 THC) derived from hemp and are using it in edibles to give consumers a mild intoxicating effect.

The FDA considers delta-8 THC an unapproved drug, but because it comes from hemp – a legal substance – its regulatory status is unclear.

“The amazing plethora of derivatives of the cannabis plant is really quite profound and astounding, and already in widespread use in a variety of means. Most of the FDA effort so far has been spent on research to figure out what the risks, if any, are of various uses of this material in its different forms,” said Califf. “The research so far has shown that there are some risks with CBD. And so, we’re going to need a different pathway than just the standard food pathway.”

FDA Kratom Info ‘Extremely Antiquated’

Califf took a similar stance on kratom, an herbal supplement that comes from the leaves of a tree that grows in Southeast Asia, where it has been used for centuries as a natural stimulant and pain reliever. An estimated two million Americans use kratom to self-treat their pain, depression, anxiety and addiction — even though the FDA has not approved kratom for any medical condition.

In a recently updated online fact sheet, the agency said kratom’s effects on the brain are similar to morphine and that kratom has “properties that expose users to the risks of addiction, abuse, and dependence.”

That brought a rebuke from Rep. Mark Pocan (D-WI), who has supported efforts to keep kratom legal. He called the FDA’s position on kratom “extremely antiquated.”

“That update was not much of an update and I think it’s being very unfair to the consumers who are legally consuming kratom in this country,” Pocan told Califf.  “Honestly, there are not only arguable conclusions (in the update), but you are linking to outdated, incomplete and inaccurate information.“

“I hope to come back to you on kratom in a couple months,” Califf replied. “There are millions of people using kratom. We do have real adverse events, real negative things that have happened to people. And it does interact with multiple neurotransmitters.”

Kratom is banned in several states, but a federal effort to ban kratom nationwide in 2016 failed due to a public outcry. The Department of Health and Human Services (HHS) later withdrew an FDA request to classify kratom as a Schedule I controlled substance, citing lack of evidence it can be abused. A former HHS official said the FDA request to schedule kratom was rejected because of “embarrassingly poor evidence & data.”

Not all federal agencies take such a dim view of kratom. A 2020 study funded by the National Institute on Drug Abuse (NIDA) concluded that kratom is an effective treatment for pain, helps users reduce their use of opioids, and has a low risk of adverse effects. NIDA recently had a public hearing on kratom to further explore its therapeutic uses.

“We’ll continue to work with NIDA and we’ll go where the science takes us,” Califf said. “But like I said with regard to cannabis products, we need something different with these kinds of products that are not traditional foods, not traditional drugs.”

Smoking Cannabis Improves Energy Levels

By Pat Anson, PNN Editor

People who frequently smoke marijuana are often portrayed in popular culture as unmotivated, low-energy slackers who spend much of their time laying in bed or bound to a couch. That stereotype of the “lazy stoner” is not only unfair – it’s inaccurate according to a new study of cannabis consumers.

In an analysis of self-reported data from people who smoked or vaporized cannabis flower to treat fatigue, researchers at the University of New Mexico found that over 91 percent reported higher energy levels soon after consuming cannabis.

"Despite the conventional beliefs that frequent cannabis use may result in decreased behavioral activity, goal-pursuit, and competitiveness, or what academics have called 'amotivational syndrome,' people tend to actually experience an immediate boost in their energy levels immediately after consuming cannabis," said co-author Jacob Miguel Vigil, PhD, a psychology professor at UNM.

The study findings, published in the journal Medical Cannabis and Cannabinoids, are the latest derived from the Releaf App, a free mobile software program that collects self-reported, real-time information from people on their use of cannabis and its effect on chronic pain, insomnia, anxiety and other medical conditions.

Fatigue is a core symptom of many chronic illnesses, including fibromyalgia, immune system disorders and myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS).

The UNM study is based on data from 3,922 cannabis sessions recorded by 1,224 people who used the Releaf app to monitor real-time changes in their symptoms and side effects.

Researchers found that people who smoked cannabis joints experienced higher energy levels than those who used a vaporizer or pipe. Surprisingly, tetrahydrocannabinol (THC) and cannabidiol (CBD) levels in the cannabis appeared to have no correlation with energy and fatigue levels. The strain of cannabis used also made little difference.     

"One of the most surprising outcomes of this study is that cannabis, in general, yielded improvements in symptoms of fatigue, rather than just a subset of products, such as those with higher THC or CBD levels or products characterized as sativa rather than indica," said co-author Sarah Stith, PhD, an economics professor at UNM.

“Our observation that the major cannabinoids tetrahydrocannabinol and cannabidiol were largely uncorrelated with changes in feelings of fatigue suggest that other minor cannabinoids and phytochemicals such as terpenes may be more influential on the effects of using cannabis than previously believed,” added Vigil.

Terpenes are aromatic compounds that give plants such as lavender and citrus their fragrance. In cannabis, terpenes have a distinctive “skunky” smell, but may be responsible for much more. Recent research found that terpenes appear to have an “entourage effect” on cannabinoids that boost their pain-relieving effects.   

“In the near future, I anticipate that patients will have the opportunity to access more individualized cannabis products, with distinct and known combinations of chemical profiles for treating their specific health needs and lifestyles," said Vigil.

In addition to boosting energy levels, researchers say cannabis helped most users feel more relaxed and peaceful. Negative side effects reported by a minority of users were dry mouth and feeling mentally foggy.   

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.