Primary Care Providers Still Reluctant to Talk About CBD

By Pat Anson, PNN Editor

Edibles, beverages and other products made with cannabidiol (CBD) went mainstream years ago, as public attitudes about cannabis changed and retailers discovered there was a growing market for CBD products.

The same is not true for primary care providers, according to a new survey that found most doctors are still reluctant to recommend CBD to their patients because of doubts about its safety and effectiveness. CBD is a chemical compound in marijuana that does not produce euphoria, but is believed to reduce pain and improve other health conditions.  

In the online survey of 236 primary care providers (PCPs) affiliated with the Mayo Clinic Healthcare Network in Minnesota, Wisconsin, Florida and Arizona, doctors said CBD was frequently brought up during medical appointments, usually by patients. But those conversations didn’t last long, because most PCPs don’t feel they have enough knowledge about CBD and are skeptical about CBD marketing claims.

PCPs in states where marijuana is legal are more receptive to patients using CBD products, while PCPs in states where marijuana is still illegal are more concerned about CBD’s side effects. But regardless of its legal status, most PCPs believe CBD is ineffective for most conditions for which it is marketed, with chronic non-cancer pain and anxiety/stress being the exceptions.

“Results from this mixed methods study show that PCPs practicing in the U.S. rarely screen for or discuss CBD use with their patients and report several barriers to engage in proactive CBD-focused practice behaviors,” wrote lead author Pravesh Sharma, MD, a pediatric psychiatrist and substance use researcher at Mayo Clinic Health System.

In a second, much smaller study, Sharma and his colleagues conducted interviews with 14 PCPs and found a number of barriers that prevent an open dialogue about CBD, including lack of time, discomfort, low-quality evidence, and CBD being a low priority.

“Our study is the first in-depth report on PCP attitudes, experiences, and practice behaviors related to CBD. The findings of our study have the potential to significantly impact future PCP practice behaviors,” they concluded.

The U.S. market for legal cannabis has grown into a $29.6 billion industry, but not much has changed over the years in terms of its acceptance in the medical community. In a 2020 survey of over 1,000 primary care patients in Vermont, only 18% rated their doctor as a good source of information about cannabis. Nearly half of the patients surveyed had used cannabis in the last year, and most of them thought cannabis was helpful for pain, anxiety, depression, arthritis, sleep and nausea.

The effectiveness of CBD is somewhat murky, because CBD products are poorly regulated and vary so much in dose, quality and whether they also have THC. While CBD may be effective temporarily in relieving pain and other symptoms, some researchers are concerned about its long-term effects on children and adolescents.  

“In fact, although CBD is widely available as an unregulated supplement, we researchers know almost nothing about its effects on the developing brain. Of note, these harms apply not only to smoking, but also to ingesting, vaping or other ways of consuming cannabis or its extracts,” Hilary Marusak, PhD, a psychiatry professor at Wayne State University, said in a recent column.

“In my view, it’s important that consumers know these risks and recognize that not everything claimed in a label is backed by science. So before you pick up that edible or vape pen for stress, anxiety, or sleep or pain control, it’s important to talk to a health care provider about potential risks.”

Unfortunately, asking a doctor may not provide many answers.

Medical Cannabis Effective but Expensive for New Zealanders

By Pat Anson, PNN Editor

Medical cannabis is very effective at relieving pain, improving sleep and reducing anxiety, according to researchers in New Zealand, who say government policies need to change to make cannabis cheaper and more accessible to Kiwis.

Researchers at the University of Otago, Victoria University and the University of Auckland surveyed and conducted interviews with 213 people who had prescriptions for cannabis under New Zealand’s medical cannabis program. Participants were asked about the quality of cannabis products they used and their effectiveness.

The study findings, published in the journal Drugs, Habits and Social Policy, show that nearly 96% reported that cannabis helped them with their medical conditions. Almost half (49%) said they were able to reduce or stop taking prescription drugs.

The most common therapeutic use of medical cannabis was pain relief and 96% of participants said it helped reduce their pain. Cannabis also helped users who had difficulty sleeping (97%) and those with mental health issues (98%).

Of the participants who took cannabis for other reasons, such as autism, attention deficit hyperactivity disorder, post-traumatic stress disorder, and difficulty eating, 98% found cannabis helpful.

"An important finding of the study was that participants either decreased or stopped their use of prescribed medicines, many of which were opioid based," said co-author Geoff Noller, PhD, a Research Fellow at Otago University's Dunedin School of Medicine. "This both reinforces that they experienced some actual effect from using cannabis in that they ceased or decreased other medications with recognized efficacy, and in the case of many of these other medications, they reduced their use of potentially more problematic medications.

"There is a place for both approaches, with the results of this study suggesting that cannabis products could have a role in treating patients with chronic pain and other conditions refractory to treatment by conventional means."

But many New Zealanders find medical cannabis difficult to obtain and rely on the black market. A recent study by the NZ Drug Foundation estimated that while over a quarter of a million Kiwis use cannabis for medical reasons, only 6% -- about 17,000 people -- obtained cannabis with a prescription.

Many doctors won’t prescribe medical cannabis and there are a limited number of products on the market, keeping prices high. The Foundation said CBD oil can cost a patient $150-350 per month, with other cannabis products costing even more.

"At present, current regulations appear to be creating problems for many New Zealanders who otherwise report positive benefits from their use of medicinal cannabis,” says Noller. "Specific barriers include cost, with currently available medicinal cannabis products being too expensive for many New Zealanders due to the compliance costs of production imposed by regulations, and also the lack of knowledge about it for physicians, leading to a reluctance to prescribe, in many cases."

To obtain medical cannabis, New Zealanders need a prescription from a doctor that spells out what cannabis products can be used and the amount. Medical cannabis can only be obtained legally from a doctor or pharmacy, although many Kiwis use a “Green Fairy” – a person who provides cannabis for a nominal fee.

Cannabis Study Finds ‘Significant Improvements’ in Physical and Mental Health

By Pat Anson, PNN Editor

The use of medical cannabis was associated with “significant improvements” in physical and mental health in a large survey of Australian adults suffering from chronic pain and other health problems.

Over 3,100 people participated in the survey. Chronic non-cancer pain was the most common condition reported (68.6%), followed by cancer pain (6%), insomnia (4.8%) and anxiety (4.2%).  

Australia has relatively stringent rules for medical cannabis. Patients have to exhaust all other forms of treatment and consult with a physician, who reviews their medical history and suitability for cannabis before writing a prescription.

Most of the prescriptions for survey participants were for cannabis products taken orally, such as oils and capsules, with only a small number for dried cannabis flower. About 80% of the cannabis products were rich in cannabidiol (CBD), with the rest dominant in tetrahydrocannabinol (THC) or a balanced mix of CBD and THC.

Patients were asked to rate their wellness and quality of life in eight categories on a scale of 0-100, including general health, body pain, physical functioning, physical limitations, mental health, emotional limitations, social functioning and vitality. The surveys were conducted at the start of the study and then every 45 days after cannabis therapy was initiated, with a total of 15 follow up surveys.   

The study findings, recently published in JAMA Network Open, showed sustained improvement in all eight wellness categories after participants started taking cannabis, with body pain improving an average of 10 to 15 points on the 100-point scale. Researchers also found “pronounced and statistically significant improvements” in mental, social and emotional health.

“This study suggests a favorable association between medical cannabis treatment and quality of life among patients with a diverse range of conditions. However, clinical evidence for cannabinoid efficacy remains limited, and further high-quality trials are required,” wrote lead author Thomas Arkell, PhD, a psychopharmacologist at the Swinburne University of Technology in Melbourne.

Adverse events such as sleepiness and dry mouth were relatively common during cannabis therapy, but were usually mild or moderate.

Before starting cannabis therapy, patients were taking an average of nearly five medications a day, the most common being simple analgesics (54%), opioids (48%), antidepressants (45%), benzodiazepines (34%) and gabapentinoids (22%). The study did not examine if medication use declined once participants started taking cannabis.  

“While we cannot exclude the possibility that adverse events may have been caused in whole or part by the disease state and concomitant medications, the relatively high incidence of adverse events still affirms the need for caution with THC prescribing and careful identification of patients with contraindications,” Arkell wrote.

Medical cannabis was legalized in Australia in 2016. Since then, over 332,000 Australians have been given cannabis prescriptions, mostly for chronic pain (55%), anxiety (23%) and sleep disorders (6%).

Pain management experts in Australia have long taken a dim view of cannabis. In 2021, the Australian and New Zealand College of Anaesthetists released new guidance urging doctors not to prescribe medical cannabis for chronic non-cancer pain because of a lack of good quality research.

Cannabis Helps Relieve Cancer Pain

By Pat Anson, PNN Editor

Good news for patients suffering from cancer pain or side effects from cancer treatment. Two new studies found that medical cannabis helps relieve cancer pain, and offer some lessons to non-cancer patients about which cannabis products might work best for them.

The first study involved 358 adult cancer patients enrolled in a cannabis registry created by the Quebec Medical College. The patients were being treated for a variety of different cancers and were referred to the registry by their doctors. The primary complaint of most was pain (72%), with others experiencing symptoms such as nausea, anorexia, weight loss, anxiety and insomnia.

Participants were assigned to one of three groups, using cannabis products that were high in tetrahydrocannabinol (THC), high in cannabidiol (CBD), or a balanced blend of THC and CBD. The cannabis was ingested orally, through inhalation or a combination of the two. Patients were monitored and assessed every three months for a year.

The study findings, published in the journal BMJ Supportive & Palliative Care, show that pain levels dropped significantly after 3, 6 and 9 months, with pain slightly worsening after 12 months. Patients using balanced THC-CBD products reported the most pain relief, and many were able to reduce their use of opioids and other medications.

A small percentage of patients suffered adverse events from cannabis, such as sleepiness, dizziness and fatigue. Only 5 patients had side effects so severe that they stopped using cannabis.

Researchers concluded that medical cannabis should have a role as a complimentary pain management option in cancer patients who don’t get adequate relief from conventional analgesics.

“We found MC (medical cannabis) to be a safe and effective treatment option to help with cancer pain relief. THC:CBD balanced products appear to perform better as compared with THC-dominant and CBD-dominant products. Furthermore, we observed consistent decreases in medication burden and opioid use in our patient population,” researchers said.

Less Pain = Better Cognition

The second study, by researchers at University of Colorado Boulder, involved 25 cancer patients being treated by oncologists at the CU Anschutz Medical Campus. The patients’ pain levels, sleep patterns, cognition and reaction times were assessed at the start of the study; and they were asked to select edible products from a cannabis dispensary, such as chocolates, gummies, tinctures and baked goods containing different ratios of THC and CBD.

After just two weeks of regular use, patients reported less pain, better sleep, and the unexpected benefit of improved cognition – they were able to think more clearly.

“When you’re in a lot of pain, it’s hard to think,” said senior author and cancer survivor Angela Bryan, PhD, a professor of psychology and neuroscience at CU Boulder. “We found that when patients’ pain levels came down after using cannabis for a while, their cognition got better.”

The improved cognition didn’t happen right away. Patients who used edibles rich in THC got high from it and their cognition initially decreased. But after a few days of regular cannabis consumption, a new pattern emerged. Patients reported improvements in pain, sleep and cognitive function, including reaction times.

“We thought we might see some problems with cognitive function,” said Bryan. “But people actually felt like they were thinking more clearly.”

Patients who ingested edibles high in CBD reported bigger improvements in sleep quality and pain intensity.

Bryan’s study, published in the journal Exploration in Medicine, is one of the first to assess the efficacy of cannabis purchased at dispensaries — rather than less potent government supplied cannabis or synthetic cannabis medications that are primarily used to treat nausea.

Bryan had just begun studying medical cannabis in 2017, when she was diagnosed with breast cancer. After surgery and chemotherapy, she looked to cannabis for pain relief as an alternative to opioids. Neuropathic pain is a common side effect from chemotherapy.

Bryan used her own customized regimen of potent THC products when pain was intense and took mostly CBD products when the pain was more manageable. She was not completely pain-free, but she didn’t take a single opioid during treatment. She hopes others will learn from her experience.

“I was extremely lucky because I had some knowledge about this. Most patients don’t,” Bryan said. “People are open to trying whatever they think might be useful, but there's just not much data out there to guide them on what works best for what.”

As many as 40% of U.S. cancer patients use cannabis, but only a third of doctors feel comfortable advising them about it.

Melatonin and Cannabis Products Often Mislabeled

By Pat Anson, PNN Editor

If you use cannabis for pain relief or take melatonin to help you sleep at night, you may want to check the label and ask the manufacturer just how accurate the list of ingredients is.  Or think twice before buying it.

Two more studies are raising doubts about the accuracy of label claims on cannabis products and melatonin supplements, which are often marketed with unsupported claims about their health benefits.

In the first study, published this week in JAMA, researchers analyzed 25 melatonin gummy products, including 5 gummies that also contained cannabidiol (CBD). Melatonin is a natural hormone produced by the brain at night to help induce sleep. Supplements containing synthetic melatonin and/or CBD are often marketed as products that improve sleep, reduce anxiety, and promote relaxation.

Researchers found that only 3 of the 25 gummies contained enough melatonin to be within 10% of the labeled amount – with one product containing 347% more melatonin than what was listed, a potentially dangerous amount. Another gummy contained no melatonin at all, just CBD.

“The great majority of melatonin gummy products were inaccurately labeled, with most products exceeding the declared amount of melatonin and CBD,” wrote lead author Pieter Cohen, MD, an associate professor at Harvard Medical School and an internist at Cambridge Health Alliance. “Given these findings, clinicians should advise parents that pediatric use of melatonin gummies may result in ingestion of unpredictable quantities of melatonin and CBD.”

Pediatric use is concerning because calls to U.S. Poison Control Centers about children ingesting melatonin have increased five-fold over the past decade, resulting in nearly 28,000 emergency room visits, over 4,000 hospitalizations and two deaths.

Researchers say it takes just 0.1 mg to 0.3 mg of melatonin to increase plasma levels beyond the normal nighttime range in young adults. The amount of melatonin found in the gummies was much higher, including one product containing 13.1 mg of melatonin.

“Consuming melatonin gummies as directed could expose children to between 40 and 130 times higher quantities of melatonin,” they said. “With respect to CBD, the drug is FDA approved to treat refractory seizures caused by 3 rare genetic disorders, but the FDA has not approved the use of CBD for any indication in healthy children.”

The JAMA report is believed to be the first U.S. study to quantify the amount of melatonin in over-the-counter supplements. A 2017 Canadian analysis of melatonin products had similar findings, with the actual dose of melatonin ranging from 17% to 478% of the amount listed on the label. Neither the U.S. or Canadian studies identified the melatonin brands that were tested.

Too Little THC

It wasn’t too much, but too little tetrahydrocannabinol (THC) that University of Northern Colorado researchers found in 23 cannabis flower products purchased at state-licensed dispensaries. The study findings, recently published in the journal PLOS One, show that nearly 70% of the flower samples had THC levels at least 15% lower than what was listed on their labels.

Inaccurate labeling has long been a problem in the cannabis industry. Some growers and merchants resort to “lab shopping” to seek out product testing laboratories that generate the most desirable results – which means inflated levels of THC.  There’s a financial incentive to do so, because cannabis products containing high amounts of THC usually sell at a higher price.

One of the flower samples, purchased at a Denver dispensary and sold under the brand name “OG Kush 2,” had only half the amount of THC listed on its label.  

“Given our results it is urgent that steps are taken to increase label accuracy of Cannabis being sold to the public. The lack of accurate reporting of THC potency can have impacts on medical patients controlling dosage, recreational consumers expecting an effect aligned with price, and trust in the industry as a whole,” researchers said.

“Although we have no power to change the current system, we hope highlighting this issue and educating consumers will affect the change needed to remedy inflated potency of flower products. Addressing this discrepancy will require both changes to the regulatory system and consumer awareness that reported THC potencies are frequently inflated.”

Although 38 states and Washington DC have legalized medical or recreational cannabis, there is little consistency in labeling, regulating or testing cannabis. The researchers called for more regulatory oversight of cannabis and standardized testing protocols.

UK Study Shows Chronic Pain Patients Benefit from Cannabis

By Pat Anson, PNN Editor

Chronic pain patients who used a variety of cannabis products experienced less pain, better sleep and improved quality of life, according to a new UK study that found the most improvement in patients who used oil-based cannabis products.

Researchers at Imperial College London assessed the safety and efficacy of cannabis in over 700 pain patients enrolled in the UK Medical Cannabis Registry. Participants were divided into three groups that used either oil-based cannabis, smoked or vaporized dried flowers, or a combination of both (CBMP) for six months. The oil-based products included extracts, lozenges and capsules.

The study findings, published in the journal Expert Review of Neurotherapeutics, show symptom improvement in all three groups, with patients using cannabis oil either alone or in combination with dried flower reporting the most improvement.

Researchers think the CBMP group derived the most benefit because the cannabis was ingested through two different administrative routes, one absorbed straight into the blood stream through inhaling (dried flowers) and the other slowly absorbed through the digestive system (oil-based cannabis).

“The findings in this study demonstrate treatment with oil-based, dried flowers, or a combination of both CBMPs are associated with statistically significant improvements in pain relief and sleep quality after 6 months in chronic pain patients,” researchers reported.

“Additionally, patients prescribed oils or both types of CBMPs experienced reduced anxiety and an improvement in their ability to perform daily activities. Patients prescribed a combination of both CBMPs recorded improvements in their self-care and mobility abilities. Collectively, this evidence signals that initiation of CBMP treatment is associated with improved HRQoL (health related quality of life).

In addition to symptom improvement, participants in the CBMP group reported a small reduction (3.28%) in their use of opioid analgesics.

About one in every four patients had an adverse side effect, such as fatigue, somnolence and dry mouth. Adverse events were more common in females, former cannabis users and cannabis naïve (new) users.  

A previous study of patients enrolled in the UK Medical Cannabis Registry found significant improvement in their pain, discomfort and sleep quality after using cannabis oil.

A recent survey of U.S. adults with chronic pain found that nearly a third have used cannabis for pain relief. Over half of those who used cannabis said it also enabled them to decrease their use of opioids and other pain medications.

More States Should Require Insurers to Pay for Medical Cannabis

By Paul Armentano, Guest Columnist

Should health insurance programs reimburse patients for their use of medical cannabis products? In a growing number of states, the courts are saying “yes.”

In the most recent example, a Pennsylvania Appellate Court ruled that workers’ compensation plans must cover cannabis-related expenditures when an employee uses it to recover from a workplace-related injury. The court ruled that employees in Pennsylvania possess “a statutory right” to be reimbursed for medical marijuana expenses that are reasonable and necessary to treat a work injury.  

“The MMA (Pennsylvania Medical Marijuana Act) specifically mandates that no medical marijuana patients be denied any rights for (the) lawful use of medical marijuana,” the Court said.

The Pennsylvania Court is not the first to issue an affirmative verdict in this matter. Courts in several states, including Connecticut, New Hampshire, New Jersey, New Mexico and New York, have provided similar opinions – determining that the denial of compensation claims would be antithetical to the legislatures’ express findings that cannabis is a state-legal therapy.

By contrast, courts in some other states, including Minnesota, have issued contradictory opinions – finding that it would be inappropriate for insurers to reimburse claimants for their use of a federally illegal substance. Federal law still classifies marijuana as a Schedule I controlled substance, placing it in the same legal category as heroin.

In most states, however, the law is largely silent on the issue. But don’t expect that to be the case for much longer. As scientific consensus and public attitudes surrounding the safety and efficacy of medical cannabis continue to evolve, the way insurers approach patients’ use of marijuana is likely to change too.

For example, lawmakers in Massachusetts recently introduced legislation explicitly providing that injured employees be reimbursed for their medical marijuana-related costs. In New York, lawmakers just advanced legislation, A. 4713, requiring public insurance plans to treat medical cannabis like any other medication. 

Thirty-eight states and the District of Columbia currently regulate the production and dispensing of cannabis for medical purposes. No state government has ever repealed or even rolled back these laws. That’s because these policies are widely accepted among both the public and among health professionals.

In fact, according to nationwide survey data recently compiled by the Centers for Disease Control and Prevention, over two-thirds of practicing physicians acknowledge the efficacy of medical cannabis and over one-quarter say that they have recommended it to their patients. 

Tens of millions of Americans are now using cannabis therapeutically. The number has doubled over the past decade, as peer-reviewed data that support the use of medical cannabis for the treatment of pain, multiple sclerosis, and other ailments has continued to grow. In many instances, patients are replacing their use of opioids, benzodiazepines and other prescription medications with cannabis because they find it more effective and with fewer adverse side effects. 

In short, most patients, most physicians, and most state laws view cannabis as a legitimate therapeutic option. Therefore, the millions of Americans who rely upon medical cannabis products ought to be afforded the same entitlements as those who use other conventional medications and therapies. Those privileges should include insurance-provided reimbursement for medical cannabis treatment.  

State legislators ought to see to it that this is a right provided for and protected in jurisdictions where medical marijuana is legally available under the law. 

Paul Armentano is the Deputy Director for NORML, the National Organization for the Reform of Marijuana Laws.

Is Cannabis Harmful During Pregnancy and Adolescence?

By Hilary Marusak, Wayne State University

Cannabis is a widely used psychoactive drug worldwide, and its popularity is growing: The U.S. market for recreational cannabis sales could surpass $72 billion by 2023.

As of early 2023, 21 U.S. states and the District of Columbia have legalized cannabis for recreational use for people age 21 and up, while 39 states plus the District of Columbia have legalized it for medical use.

The growing wave of legalization and the dramatic increase in cannabis potency over the past two decades have raised concerns among scientists and public health experts about the potential health effects of cannabis use during pregnancy and other vulnerable periods of development, such as the teen years.

I am a developmental neuroscientist specializing in studying what’s known as the endocannabinoid system. This is an evolutionarily ancient system found in humans and other vertebrates that produces natural cannabinoids such as THC and CBD.

Cannabis and its constituents interact with the body’s endocannabinoid system to product their effects. THC and CBD are the most commonly known cannabis extracts and can be synthesized in a lab. My lab also studies the risks versus potential therapeutic value of cannabis and cannabinoids.

Potential Health Risks

People often assume there’s no risk when using cannabis or cannabinoids during vulnerable periods of life, but they’re basing that on little to no data. Our research and that of others suggests that cannabis use during pregnancy and adolescence can present myriad health risks the public should be aware of.

Data shows that many people who use cannabis continue to do so during pregnancy. But there are health risks. More and more pregnant people are using cannabis today compared with a decade ago, with some studies showing that nearly 1 in 4 pregnant adolescents report that they use cannabis.

Many cannabis-using people may have not known they were pregnant and stopped using when they found out. Others report using cannabis for its touted ability to ease pregnancy-related symptoms, like nausea and anxiety. However, studies do not yet confirm those health claims. What’s more, the potential harms are often downplayed by pro-cannabis marketing and messaging by dispensaries, advocacy groups and even midwives or doulas.

In addition, physicians and other health care providers often are not knowledgeable enough or don’t feel well equipped to discuss the potential risks and benefits of cannabis with their patients, including during pregnancy.

While research shows that most people who are pregnant perceive little to no risk in using cannabis during pregnancy, the data show there is clear cause for concern. Indeed, a growing number of studies link prenatal cannabis exposure to greater risk of preterm birth, lower birth weight and psychiatric and behavioral problems in children. These include, for example, difficulties with attention, thought, social problems, anxiety and depression.

Cannabis and Brain Development

When cannabis is inhaled, consumed orally or taken in through other routes, it can easily cross through the placenta and deposit in the fetal brain, disrupting brain development.

A recent study from my lab, led by medical student Mohammed Faraj, found that cannabis use during pregnancy can shape the developing brain in ways that are detectable even a decade later.

We used data from the National Institutes of Health Adolescent Brain Cognitive Development Study, which is the largest long-term study of brain development and child and adolescent health in the U.S. It has followed more than 10,000 children and their families from age 9-10 over a 10-year period.

Through that analysis, we linked prenatal cannabis exposure to alterations in functional brain networks in 9- and 10-year-old children. In particular, prenatal cannabis exposure appeared to disrupt the communication between brain networks involved in attentional control, which may explain why children who were exposed to cannabis in utero may develop difficulties with attention or other behavioral issues or mental disorders as they develop.

While alcohol abuse has steadily declined among adolescents since 2000 in the U.S., cannabis use shows the opposite pattern: It increased by 245% during that same period.

Data reported in 2022 from the Monitoring the Future survey of over 50,000 students in the U.S. found that nearly one-third of 12th grade students reported using cannabis in the past year, including cannabis vaping. Yet only about 1 in 4 12th grade students perceive great harm in using cannabis regularly. This suggests that many teens use cannabis, but very few consider it to have potential negative effects.

Research shows that the adolescent brain is primed to engage in high-risk behaviors such as experimenting with cannabis and other substances. Unfortunately, owing to ongoing brain development, the adolescent brain is also particularly susceptible to the effects of cannabis and other substances. Indeed, many neuroscientists now agree that the brain continues to develop well into the second and even third decade of life.

In line with this vulnerability, research shows that, relative to those who did not use cannabis during adolescence, those who started using it during adolescence are at increased risk of developing depression, suicidal ideation, psychosis and reductions in IQ during adolescence and adulthood. Neuroimaging studies also show residual effects of adolescent cannabis use on brain functioning, even later during adulthood.

‘No Amount Is Safe’

Despite common misconceptions that cannabis is “all natural” and safe to use during pregnancy or adolescence, the data suggests there are real risks. In fact, in 2019, the U.S. surgeon general issued an advisory against the use of cannabis during pregnancy and adolescence, stating that “no amount … is known to be safe.”

Cannabis may be harmful to the developing brain because it disrupts the developing endocannabinoid system, which plays a critical role in shaping brain development from conception and into adulthood. This includes neural circuits involved in learning, memory, decision-making and emotion regulation.

While much of this research has focused on cannabis use, there is also other research that comes to similar conclusions for THC and CBD in other forms. In fact, although CBD is widely available as an unregulated supplement, we researchers know almost nothing about its effects on the developing brain. Of note, these harms apply not only to smoking, but also to ingesting, vaping or other ways of consuming cannabis or its extracts.

In my view, it’s important that consumers know these risks and recognize that not everything claimed in a label is backed by science. So before you pick up that edible or vape pen for stress, anxiety, or sleep or pain control, it’s important to talk to a health care provider about potential risks – especially if you are or could be pregnant or are a teen or young adult.

Hilary Marusak, PhD, is an Assistant Professor of Psychiatry and Behavioral Neurosciences at Wayne State University. She directs the WSU THINK Lab, which focuses on pediatric anxiety and understanding the impact of childhood trauma on neural development. Dr. Marusak receives funding from the National Institutes of Health and the State of Michigan.   

This article originally appeared in The Conversation and is republished with permission.

Our Bodies Produce Chemicals Similar to THC in Cannabis

By Drs. Prakash and Mitzi Nagarkatti, University of South Carolina

Over the past two decades, a great deal of attention has been given to marijuana – also known as pot or weed. As of early 2023, marijuana has been legalized for recreational use in 21 states and Washington, D.C., and the use of marijuana for medical purposes has grown significantly during the last 20 or so years.

But few people know that the human body naturally produces chemicals that are very similar to delta-9-tetrahydrocannabinol, or THC, the psychoactive compound in marijuana, which comes from the Cannabis sativa plant. These substances are called endocannabinoids, and they’re found across all vertebrate species.

Evolutionarily, the appearance of endocannabinoids in vertebrate animals predates that of Cannabis sativa by about 575 million years.

It is as if the human body has its own version of a marijuana seedling inside, constantly producing small amounts of endocannabinoids.

The similarity of endocannabinoids to THC, and their importance in maintaining human health, have raised significant interest among scientists to further study their role in health and disease, and potentially use them as therapeutic targets to treat human diseases.

THC was first identified in 1964, and is just one of more than 100 compounds found in marijuana that are called cannabinoids.

What Are Endocannabinoids?

Endocannabinoids were not discovered until 1992. Since then, research has revealed that they are critical for many important physiological functions that regulate human health. An imbalance in the production of endocannabinoids, or in the body’s responsiveness to them, can lead to major clinical disorders, including obesity as well as neurodegenerative, cardiovascular and inflammatory diseases.

We are immunologists who have been studying the effects of marijuana cannabinoids and vertebrate endocannabinoids on inflammation and cancer for more than two decades. Research in our laboratory has shown that endocannabinoids regulate inflammation and other immune functions.

A variety of tissues in the body, including brain, muscle, fatty tissue and immune cells, produce small quantities of endocannabinoids. There are two main types of endocannabinoids: anandamide, or AEA, and 2-arachidonoyl glycerol, known as 2-AG. Both of them can activate the body’s cannabinoid receptors, which receive and process chemical signals in cells.

One of these receptors, called CB1, is found predominantly in the brain. The other, called CB2, is found mainly in immune cells. It is primarily through the activation of these two receptors that endocannabinoids control many bodily functions.

The receptors can be compared to a “lock” and the endocannabinoids a “key” that can open the lock and gain entry into the cells. All these endocannabinoid receptors and molecules together are referred to as the endocannabinoid system.

The cannabis plant contains another compound called cannabidiol, or CBD, which has become popular for its medicinal properties. Unlike THC, CBD doesn’t have psychoactive properties because it does not activate CB1 receptors in the brain. Nor does it activate the CB2 receptors, meaning that its action on immune cells is independent of CB2 receptors.

Endocannabinoids Help Us Feel Better

The euphoric “high” feeling that people experience when using marijuana comes from THC activating the CB1 receptors in the brain.

But when endocannabinoids activate CB1 receptors, by comparison, they do not cause a marijuana high. One reason is that the body produces them in smaller quantities than the typical amount of THC in marijuana. The other is that certain enzymes break them down rapidly after they carry out their cellular functions.

However, there is growing evidence that certain activities may release mood-elevating endocannabinoids. Some research suggests that the relaxed, euphoric feeling you get after exercise, called a “runner’s high,” results from the release of endocannabinoids rather than from endorphins, as previously thought.

The endocannabinoids regulate several bodily functions such as sleep, mood, appetite, learning, memory, body temperature, pain, immune functions and fertility. They control some of these functions by regulating nerve cell signaling in the brain. Normally, nerve cells communicate with one another at junctions called synapses. The endocannabinoid system in the brain regulates this communication at synapses, which explains its ability to affect a wide array of bodily functions.

Research in our laboratory has shown that certain cells of the immune system produce endocannabinoids that can regulate inflammation and other immune functions through the activation of CB2 receptors.

In addition, we have shown that endocannabinoids are highly effective in lessening the debilitating effects of autoimmune diseases. These are diseases in which the immune system goes haywire and starts destroying the body’s organs and tissues. Examples include multiple sclerosis, lupus, hepatitis and arthritis.

Chronic Pain Linked to Low Levels of Endocannabinoids

Recent research suggests that migraine, fibromyalgia, irritable bowel syndrome, post-traumatic stress disorder and bipolar disease are all linked to low levels of endocannabinoids.

In a 2022 study, researchers found that a defect in a gene that helps produce endocannabinoids causes early onset of Parkinson’s disease. Another 2022 study linked the same gene defect to other neurological disorders, including developmental delay, poor muscle control and vision problems.

Other research has shown that people with a defective form of CB1 receptors experience increased pain sensitivity such as migraine headaches and suffer from sleep and memory disorders and anxiety.

We believe that the medicinal properties of THC may be linked to the molecule’s ability to compensate for a deficiency or defect in the production or functions of the endocannabinoids.

For example, scientists have found that people who experience certain types of chronic pain may have decreased production of endocannabinoids. People who consume marijuana for medicinal purposes report significant relief from pain. Because the THC in marijuana is the cannabinoid that reduces pain, it may be helping to compensate for the decreased production or functions of endocannabinoids in such patients.

Deciphering the role of endocannabinoids is still an emerging area of health research. Certainly much more research is needed to decipher their role in regulating different functions in the body.

In our view, it will also be important to continue to unravel the relationship between defects in the endocannabinoid system and the development of various diseases and clinical disorders. We think that the answers could hold great promise for the development of new therapies using the body’s own cannabinoids.

Prakash Nagarkatti, PhD, and Mitzi Nagarkatti, PhD, are Professors of Pathology, Microbiology and Immunology at the University of South Carolina. They receive funding from the National Science Foundation and the National Institutes of Health.

This article originally appeared in The Conversation and is republished with permission.

DEA Considers Synthetic THC Illegal

By Pat Anson, PNN Editor

The Drug Enforcement Administration considers a synthetic form of THC — the psychoactive compound in cannabis and hemp — a controlled substance that is illegal under federal law.

Hemp was legalized federally under the 2018 Farm Bill, in part because hemp contains only trace amounts of THC. However, some companies developed a synthetic form of hemp-derived THC — called THC acetate ester (THCO) — to give consumers an intoxicating effect. Because THCO was modeled after the THC found in hemp, they claimed it could be legally sold and consumed.

However, in a recent letter to Rod Kight, an attorney who specializes in cannabis law, the head of the DEA’s Drug & Chemical Evaluation Section said the agency considers delta-8 and delta-9 products containing THCO to be Schedule I controlled substances, which are illegal to sell or possess.

“Delta-9-THCO and delta-8-THCO do not occur naturally in the cannabis plant and can only be obtained synthetically, and therefore do not fall under the definition of hemp. Delta-9-THCO and delta-8-THCO are tetrahydrocannabinols having similar chemical structures and pharmacological activities to those contained in the cannabis plant,” the letter states.

Kight said he’s been telling clients and personal friends that THCO is potentially dangerous.

“Although I do not always agree with the DEA’s view on cannabis matters, I agree with this opinion and, frankly, am not surprised,” he wrote.  “It has always been my view that THCO is a controlled substance under federal law. Although it can be made from cannabinoids from hemp, THCO is not naturally expressed by the hemp plant. It is a laboratory creation that does not occur in nature, at least not from the hemp plant.”

As Kight points out in his blog, the DEA letter does not address delta-8 or delta-9 THC, which are natural and derived from hemp. Although those substances are considered legal at the federal level, over a dozen states have banned products containing them.

In states where they remain legal, delta-8 and 9 are widely available in candy, gummies, cookies, tinctures and beverages. Some companies claim the products have “uniquely potent effects on pain” and other health conditions, even while admitting there is little evidence to support those claims.

The FDA became so alarmed by the profusion of delta-8 and delta-9 THC products — and their marketing to children — that it sent letters to five companies in 2022 warning them to stop making unsubstantiated medical claims.

"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.”

The FDA says it had received over 100 reports of adverse events involving delta-8 THC, with poison control centers reporting over 2,300 cases, including one that involved the death of a child.

Florida Study Blames Cannabis for Hundreds of Deaths

By Pat Anson, PNN Editor

Advocates of medical marijuana – or cannabis use in general – have long said you can’t overdose on cannabis and that the natural plant is even “safer than many foods.”   

But researchers at Florida Atlantic University say cannabis products – particularly synthetic cannabis – are riskier than many people believe. In a study recently published in the Journal of Nursing Scholarship, they called cannabis “a legitimate public health concern” that has killed hundreds of Floridians in recent years.  

Analyzing 2014 to 2020 data from the Florida Department of Law Enforcement, researchers found that 386 people died as a result of drug intoxication caused by cannabis use. It’s important to note that the vast majority of those deaths (98.7%) involved accidents such as motor vehicle crashes, with a handful of deaths caused by murder or suicide. No overdoses were reported.

Most of the Florida deaths also involved other substances such as alcohol, opioids, heroin and cocaine. In nearly two-thirds of the deaths, synthetic cannabinoids such as K2 or Spice were involved. Synthetic cannabinoids are chemicals sprayed onto dried, shredded leaves that mimic the effect of cannabis, but are often quite stronger.  

“Synthetic cannabinoids are part of the new psychoactive substances that are two to 100 times more potent than THC, the main psychoactive compound in marijuana,” said lead author Armiel Suriaga, PhD, an assistant professor in FAU’s College of Nursing.

Suriaga and his colleagues found that over 13 percent of those who died had cardiac-related conditions such as high blood pressure, atherosclerosis, cardiac arrhythmias or an enlarged heart. There was one death from an ischemic stroke and one death from a hemorrhagic stroke, both related to synthetic cannabis use.

“The persistent deaths from cannabis and synthetic cannabis use are a legitimate public health concern,” said Suriaga. “The public should remain vigilant of the adverse health outcomes associated with these substances and their unpredictable effects, especially for men who are disproportionately affected, and particularly for people with underlying cardiovascular and respiratory conditions.”

‘Misleading and Sensational’ Study

Marijuana advocates say it was unfair of the researchers to include synthetic cannabis in their study, which was funded by the National Institutes on Drug Abuse and the American Association of Colleges of Nursing. 

“To lump in adverse effects from synthetically produced compounds in this analysis is misleading and sensational, as these products are not cannabis and their safety profile is not at all comparable to that of natural cannabis,” said Paul Armentano, Deputy Director of NORML.

“Cannabis is psychoactive and that is why advocacy groups opine in favor of its regulation, including the imposition of age controls and product testing for purity and potency. Adverse effects from cannabis, like dysphoria (anxiety), are possible but are best mitigated by regulation and education — not by criminal prohibition.”

Previous studies have looked at the relationship between cannabis and motor vehicle accidents, with mixed results. A survey of people in Michigan who used medical marijuana for chronic pain found that over half had driven while under the influence of cannabis, and one in five say they've driven while “very high.”

Other studies found a decrease in traffic fatalities in states that legalized medical marijuana. That may be because patients were substituting cannabis for alcohol and other drugs used to relieve their symptoms.

Medical Cannabis Reduced Opioid Use in High Dose Patients

By Pat Anson, PNN Editor

In recent years, there have been several studies and surveys – most of them anecdotal -- suggesting that cannabis reduces the need for opioid pain medication. A large new study takes that research a step further, finding direct evidence that chronic pain patients, including those on high doses, significantly reduced their opioid use once they started using medical cannabis.

Researchers with the New York State Department of Health and University of Albany School of Public Health followed over 8,100 patients on long-term opioid therapy (LOT) after they began using medical cannabis. All of the patients had been on opioids for at least 120 days, including some on relatively high daily doses of 90 or more morphine milligram equivalents (MME).

Researchers found that average daily doses declined significantly over time, especially for patients on high opioid doses. After eight months of using medical cannabis (MC), patients taking over 90 MME saw their daily doses fall by nearly 70 percent, compared to a 29% reduction in those getting 50 to 90 MME and a 15% reduction in those on 50 MME or less.

“This cohort study found that receiving MC for longer was associated with opioid dosage reductions. The reductions were larger among individuals who were prescribed higher dosages of opioids at baseline. These findings contribute robust evidence for clinicians regarding the potential benefits of MC in reducing the opioid burden for patients receiving LOT and possibly reduce their risk for overdose,” researchers reported in JAMA Network Open.

The study has some weaknesses. Researchers did not track the pain levels of patients or the types of pain conditions they suffered from. Also unknown is the dose or types of cannabis products they consumed.   

Although the study was conducted at a time when patients nationwide were losing access to opioids or having their doses reduced, researchers say it is “highly unlikely” that impacted their findings because the dosage decline for their patients didn’t begin until they started consuming cannabis.  

Marijuana advocates cheered the study findings.  

“The relationship between cannabis and opioid use is among of the best-documented aspects of marijuana policy,” Paul Armentano, Deputy Director of NORML, said in a statement. “In short, the science demonstrates that marijuana is a relatively safe and effective pain reliever — and that patients with legal access to it consistently reduce their use of prescription opioid medications.” 

A similar study of over 500 chronic pain patients being treated at medical cannabis clinics found a significant decline in their pain levels. And 85% of patients reported they either reduced or stopped using opioids.

A Third of Chronic Pain Sufferers Used Cannabis for Pain Relief

By Pat Anson, PNN Editor

Nearly a third of U.S. adults (31%) with chronic pain have used cannabis as an analgesic, according to a new survey that found over half of those who used cannabis said it enabled them to decrease their use of opioid medication and other pain therapies.

The survey findings, published JAMA Network Open, involved 1,724 people with chronic non-cancer pain who live in the 36 states (and Washington DC) that have legalized medical marijuana.

Unlike other studies that only focused on cannabis reducing opioid use, this survey found that over half of pain sufferers using cannabis also reduced or stop using non-opioid prescription pain relievers and over-the-counter analgesics. Many respondents also reported decreasing their use of physical therapy (39%), cognitive behavioral therapy (26%) and meditation (19%).  

“Most persons who used cannabis as a treatment for chronic pain reported substituting cannabis in place of other pain medications including prescription opioids,” wrote lead author Mark Bicket, MD, an Assistant Professor in the Department of Anesthesiology, University of Michigan School of Medicine.

“The high degree of substitution of cannabis with both opioid and nonopioid treatment emphasizes the importance of research to clarify the effectiveness and potential adverse consequences of cannabis for chronic pain. Our results suggest that state cannabis laws have enabled access to cannabis as an analgesic treatment despite knowledge gaps in use as a medical treatment for pain.”

The survey did not ask whether respondents smoked, vaped or ingested cannabis products, so there’s no way to tell which method was more effective at reducing pain. Nevertheless, it adds to a growing body of evidence that cannabis reduces pain and helps pain sufferers decrease their use of medications and other therapies.  

“Cannabis has established efficacy in the treatment of multiple conditions, including chronic pain, and it possesses a safety profile that is either comparable or superior to other controlled substances,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group.

“So it is no wonder that those with legal access to it are substituting cannabis in lieu of other, potentially less effective and more harmful substances. As legal access continues to expand, one would expect the cannabis substitution effect to grow even more pronounced in the future.”

Several previous studies have also found that cannabis users often reduce their use of prescription opioids. A large survey conducted last year found that most medical marijuana users either stopped (42%) or reduced (37%) their use of opioids. A small number were also able to stop using psychiatric medications for anxiety, depression and PTSD.  

Another recent study at Cornell University found that legalization of recreational marijuana in 11 states led to significantly reduced prescribing for Medicaid patients for a broad range of medications used to treat pain, depression, anxiety, seizures and other health conditions.

A 2021 Harris Poll found that twice as many Americans are using cannabis or CBD to manage their pain than opioids.

Guideline Recommends Surgery Patients Be Screened for Cannabis Use

By Pat Anson, PNN Editor

New medical guidelines recommend that all patients undergoing anesthesia should be screened for cannabis use before surgery, and that procedures should be delayed if patients are thought to be under the influence or impaired.

The guideline by the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine) is intended for anesthesiologists. It was developed by a panel of experts that included anesthesiologists, pain specialists and a patient advocate to deal with the growing number of people using either recreational or medical marijuana. An estimated 10% of Americans use cannabis monthly.

“Before surgery, anesthesiologists should ask patients if they use cannabis – whether medicinally or recreationally – and be prepared to possibly change the anesthesia plan or delay the procedure in certain situations,” Samer Narouze, MD, ASRA Pain Medicine president, said in a statement.

“They also need to counsel patients about the possible risks and effects of cannabis. For example, even though some people use cannabis therapeutically to help relieve pain, studies have shown regular users may have more pain and nausea after surgery, not less, and may need more medications, including opioids, to manage the discomfort. We hope the guidelines will serve as roadmap to help better care for patients who use cannabis and need surgery.”

The guideline recommends that patients be asked about their cannabis use before surgery, including whether it was smoked or ingested, the amount used, how recently it was used, and the frequency of use. It does not endorse drug testing of patients, meaning patients would have to be taken at their word.

If a patient admits recently smoking cannabis, the guideline recommends that non-emergency, elective procedures be postponed for a minimum of two hours because of the increased risk of a heart attack before, during and after surgery.

“In my opinion, these guidelines appear to be overly cautious at best and discriminatory at worst,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group. “The relationship between cannabis and opioids is well-established, with nearly 100 papers in the literature showing that pain patients typically reduce or eliminate their intake of opioids over time following cannabis use.” 

Armentano cited a recent pilot study that found people who use cannabis respond no differently to local anesthesia than those who do not. Local anesthesia is different from general anesthesia because patients remain conscious during a procedure such as dental work. 

The evidence on cannabis and general anesthesia is rather thin, and because of that the ASRA guideline gives low grades to several of its recommendations, including the one about delaying surgery.  No recommendations are made about tapering cannabis use before or after surgery, or whether to prescribe opioids to patients who use cannabinoids due to “current lack of evidence.” Anesthesiologists are instead urged to use their own clinical judgement.   

In 2020, the Perioperative Pain and Addiction Interdisciplinary Network (PAIN) released more restrictive guidelines about cannabis use, recommending that heavy cannabis use be tapered or stopped before surgery.

Cannabis Works No Better Than Placebo in Pain Studies

By Pat Anson, PNN Editor

The placebo effect is responsible for much of the pain relief experienced by participants in clinical trials of cannabis, according to new analysis that also found a “strong positive bias” in media coverage of the studies.

Researchers at the Karolinska Institute in Sweden analyzed the results of 20 placebo-controlled studies of cannabis products involving almost 1,500 people with chronic pain conditions. The cannabis products were administered as pills, sprays, oils, smoke or vapor; and most of the studies were conducted in the United States, UK or Canada.

Researchers found that many participants reported significant pain relief, but there were no differences in pain reduction between those who used cannabis products and those who used a placebo, a sham treatment that should have no effect.

“There is a distinct and clinically relevant placebo response in studies of cannabis for pain,” says Filip Gedin, PhD, a researcher in the Department of Clinical Neuroscience at Karolinska and lead author of the study published in JAMA Network Open.

Gedin and his colleagues also examined coverage the 20 studies received in the news media using Altmetric, a method of evaluating mentions in the media as either positive, negative or neutral. They did not identify the publishers of the 136 news articles that were analyzed or provide any examples of their coverage.

Researchers found that the cannabis studies received much greater media attention than other clinical studies and tended to be more positive, regardless of what the studies’ outcomes actually were. The media coverage of cannabis was so positive, in fact, that researchers wonder if it might influence findings in future studies.  

“The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief,” Gedin wrote. “We therefore consider this question to be of high importance, as the positive reporting toward cannabinoids regardless of study quality and effect size may subsequently lead to increased expectations that may ultimately influence the outcomes in clinical trials.”

The placebo effect is a well-documented but poorly understood condition in which a patient responds to a sham drug or treatment that should have no therapeutic value. A 2018 study at Northwestern University, for example, found that about half of patients who took a sugar pill they thought was an analgesic had a 30% reduction in pain – a level considered good enough for an actual painkiller.    

In another study, researchers identified some participants as “placebo responders” who are more likely to respond to a sugar pill because their brains react differently – which may explain why some patients find a medication effective and others don’t.    

Whatever the cause, researchers at the Karolinska Institute say more effort is needed to understand the placebo effect and how media coverage could make it even more potent.

“We cannot say with 100% certainty that media coverage is responsible for the high placebo response observed in our review,” Gedin wrote in an op/ed published in The Conversation.

“But given placebos were shown to be just as good as cannabis for managing pain, our results show just how important it is to think about the placebo effect and how it can be influenced by external factors – such as media coverage. For treatments, such as cannabinoids, that receive a lot of media attention, we need to be extra rigorous in our clinical trials.”