Study Finds CBD Ineffective for Chronic Pain

By Pat Anson, PNN Editor

There is little evidence that cannabidiol (CBD) products relieve chronic pain and some could be potentially harmful to patients, according to UK and Canadian researchers.

CBD is one of the chemical compounds found in cannabis, but it doesn’t have the same intoxicating effect as tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana. Often marketed as a pain reliever, CBD can be purchased in edibles, beverages, lotions, oils and other products, usually without a prescription.  

“CBD presents consumers with a big problem,” says lead author Chris Eccleston, PhD, Professor of Pain Science at the University of Bath in the UK. “It’s touted as a cure for all pain but there’s a complete lack of quality evidence that it has any positive effects.

“There should be no excuses for misleading the public, and yet it is likely that the public is being misled and possibly placed in harm’s way.”

Eccleston and his colleagues reviewed the results of 16 high-quality clinical trials of CBD products, involving over 900 participants. Their findings, published in in The Journal of Pain, show that CBD provided little or no pain relief in 15 of the 16 studies. The one small trial that did showed improvement in arthritis pain after two weeks of treatment with a topical CBD lotion.

Just as concerning to researchers is that many CBD products sold directly to consumers have significantly more or less CBD than what their labels indicate. Some CBD products also contain THC, when they weren’t supposed to have any.

“There is no good reason for thinking that CBD relieves pain, but there are good reasons for doubting the contents of CBD products in terms of CBD content and purity,” Eccleston wrote. “Regulatory authorities should also take note of the considerable deficiencies existing in the products sold, especially the incorrect labeling of many products, and possible contamination with psychoactive compounds.”

The researchers say regulators in the US, UK and Canada are often slow to respond to the false medical claims of some CBD manufacturers. The FDA occasionally sends warning letters to companies making unsubstantiated claims about CBD, but it rarely results in fines or disciplinary action.

“What this means is that there are no consumer protections,” said co-author Dr Andrew Moore, Director of Pain Research at the University of Oxford. “And without a countervailing body to keep the CBD sellers in check, it’s unlikely that the false promises being made about the analgesic effects of CBD will slow down in the years ahead.”

In a recent review, the FDA said there was “credible scientific support” for cannabis as a pain reliever and recommended that the DEA reschedule it as a Schedule III controlled substance. Such a move would make it legal under federal law for cannabis to be prescribed for medically approved conditions, but would have no impact on CBD products.

In 2022, FDA Commissioner Dr. Robert Califf asked Congress to give his agency the authority to more closely regulate CBD, but no such legislation has been passed. Eccleston says its part of a pattern in which pain sufferers are neglected and left on their own to find relief.

“It’s almost as if chronic pain patients don’t matter, and that we’re happy for people to trade on hope and despair,” he said.

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.

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.

Why Cannabis Holds Promise for Pain Management

By Benjamin Land, University of Washington Center for Cannabis Research

Drug overdose deaths from opioids continue to rise in the U.S. as a result of both the misuse of prescription opioids and the illicit drug market.

But an interesting trend has developed: Opioid emergency room visits drop by nearly 8% and opioid prescriptions are modestly lower in states where marijuana is legalized.

Marijuana is produced by the cannabis plant, which is native to Asia but is now grown throughout the world. Individuals use marijuana for both its psychoactive, euphoria-inducing properties and its ability to relieve pain.

Chemicals produced by the cannabis plant are commonly known as cannabinoids. The two primary cannabinoids that occur naturally in the cannabis plant are THC – the psychoactive compound in marijuana – and CBD, which does not cause the sensation of being high.

Many marijuana users say they take it to treat pain, suggesting that readily available cannabinoids could potentially be used to offset the use of opioids such as morphine and oxycodone that are commonly used in pain treatment. A safer, natural alternative to opioid painkillers would be an important step toward addressing the ongoing opioid epidemic.

Intriguingly however, research suggests that cannabis use could also lessen the need for opioids directly by interacting with the body’s own natural opioid system to produce similar pain-relief effects.

I am a neuropharmacology scientist who studies both opioids and cannabinoids as they relate to pain treatment and substance abuse. My research focuses on the development of drug compounds that can provide chronic pain relief without the potential for overuse and without the tapering off of effectiveness that often accompanies traditional pain medications.

How Opioids Work

Our bodies have their own built-in opioid system that can aid in managing pain. These opioids, such as endorphins, are chemicals that are released when the body experiences stress such as strenuous exercise, as well as in response to pleasurable activities like eating a good meal. But it turns out that humans are not the only organisms that can make opioids.

In the 1800s, scientists discovered that the opioid morphine – isolated from opium poppy – was highly effective at relieving pain. In the last 150 years, scientists have developed additional synthetic opioids like hydrocodone and dihydrocodeine that also provide pain relief.

Other opioids like heroin and oxycodone are very similar to morphine, but with small differences that influence how quickly they act on the brain. Fentanyl has an even more unique chemical makeup. It is the most powerful opioid and is the culprit behind the current surge in drug overdoses and deaths, including among young people.

Opioids, whether naturally produced or synthetic, produce pain relief by binding to specific receptors in the body, which are proteins that act like a lock that can only be opened by an opioid key.

One such receptor, known as the mu-opioid receptor, is found on pain-transmitting nerve cells along the spinal cord. When activated, mu-receptors tamp down the cell’s ability to relay pain information. Thus, when these opioids are circulating in the body and they reach their receptor, stimuli that would normally cause pain are not transmitted to the brain.

These same receptors are also found in the brain. When opioids find their receptor, the brain releases dopamine – the so-called “feel-good” chemical – which has its own receptors. This is in part why opioids can be highly addicting. Research suggests that these receptors drive the brain’s reward system and promote further drug-seeking. For people who are prescribed opiates, this creates the potential for abuse.

Opioid drugs, which include heroin, oxycodone and fentanyl, are highly addictive.

Opioid receptors are dynamically regulated, meaning that as they get exposed to more and more opioids, the body adapts quickly by deactivating the receptor. In other words, the body needs more and more of that opioid to get pain relief and to produce the feel-good response. This process is known as tolerance. The drive to seek more and more reward paired with an ever-increasing tolerance is what leads to the potential for overdose, which is why opioids are generally not long-term solutions for pain.

How THC and CBD Relieve Pain

Both THC and CBD have been shown in numerous studies to lessen pain, though – importantly – they differ in which receptors they bind to in order to produce these effects.

THC binds to cannabinoid receptors that are located throughout the central nervous system, producing a variety of responses. One of those responses is the high associated with cannabis use, and another is pain relief. Additionally, THC is believed to reduce inflammation in a manner similar to anti-inflammatory drugs like ibuprofen.

In contrast, CBD appears to bind to several distinct receptors, and many of these receptors can play a role in pain reduction. Importantly, this occurs without the high that occurs with THC.

Because they target different receptors, THC and CBD may be more effective working in concert rather than alone, but more studies in animal models and humans are needed.

Cannabinoids may also be helpful for other conditions as well. Many studies have demonstrated that cannabinoid drugs approved for medical use are effective for pain and other symptoms like spasticity, nausea and appetite loss.

Along with the pairing of THC and CBD, researchers are beginning to explore the use of those two cannabinoids together with existing opioids for pain management. This research is being done in both animal models and humans.

These studies are designed to understand both the benefits – pain relief – and risks – primarily addiction potential – of co-treatment with cannabinoids and opioids. The hope would be that THC or CBD may lower the amount of opioid necessary for powerful pain relief without increasing addiction risk.

For example, one study tested the combination of smoked cannabis and oxycontin for pain relief and reward. It found that co-treatment enhanced pain relief but also increased the pleasure of the drugs. This, as well as a limited number of other studies, suggests there may not be a net benefit.

However, many more studies of this type will be necessary to understand if cannabinoids and opioids can be safely used together for pain. Still, using cannabinoids as a substitution for opioids remains a promising pain treatment strategy.

The next decade of research will likely bring important new insights to the therapeutic potential of cannabinoids for chronic pain management. And as marijuana legalization continues to spread across the U.S., its use in medicine will undoubtedly grow exponentially.

Benjamin Land, PhD is a Research Associate Professor of Pharmacology at the University of Washington School of Medicine and the UW Center for Cannabis Research. Land receives funding from the National Institutes of Health for cannabinoid research, and has received cannabinoid related funding from the University of Washington Addiction and Drug Abuse Institute and SCAN Design Foundation.

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

Smoking Marijuana More Effective Than CBD Extracts for Back Pain

By Pat Anson, PNN Editor

One of the reasons many medical marijuana users prefer edibles over smoking is that they are perceived as healthier.  Marijuana smoke contains many of the same chemicals and carcinogens as cigarette smoke, and could have harmful effects on people with respiratory or cardiovascular problems.

But a small new study conducted in Israel found that smoking marijuana is better than ingesting it, at least when it comes to treating chronic lower back pain. Researchers enrolled 24 adults with MRI or CT scans that showed evidence of disc herniation or spinal stenosis, and had them try two different types of cannabis treatment.

The first was a cannabis extract rich in cannabidiol (CBD), which was taken sublingually under the tongue daily for 10 months. After a month of no treatment, the same group smoked cannabis flowers rich in tetrahydrocannabinol (THC) up to four times a day for 12 months. Participants were allowed to take pain medication as needed, including oxycodone and acetaminophen.

The study findings, published in the Rambam Maimonides Medical Journal, showed there was little to no improvement in back pain when participants took the extract, but significant improvement when they smoked cannabis. The use of analgesic drugs also dropped significantly while smoking.

Notably, three patients dropped out of the extract phase of the study because it wasn’t helping them, but then returned to participate in the smoking phase.

“The current study is the first, to our knowledge, to indicate that THC-rich smoked therapy is more advantageous in ameliorating LBP (lower back pain), than low THC CBD-rich sublingual extracts. Despite the small number of patients, our data indicate that THC-rich smoked therapy is helpful in mitigating LBP,” researchers reported.

The most commonly reported adverse events during the study were nausea, dizziness, drowsiness and fatigue during the extract phase; sore throat and drowsiness were reported during the smoking phase. All of the adverse symptoms disappeared after a dose tolerance was reached. Most of the adverse effects were in female patients.

A 2019 study of medical marijuana users also found that smoking cannabis provided more pain relief than ingesting it. Over 3,300 people logged their symptoms on a mobile app while using a variety of cannabis products, including dried flower, edibles, tinctures and ointments. Smoking the dried flower provided more pain relief than any other cannabis product, regardless of the amount of THC.

Another problem with CBD edibles is that they are frequently mislabeled. A recent study of 80 CBD oils found that only 43 had concentrations of cannabidiols that were within 10% of their label claims – an accuracy rate of just 54 percent.

Lab Mice Agree: Delta-8 Just Like Taking Delta-9

By Pat Anson, PNN Editor

Laboratory mice at a research facility have figured out something that Congress failed to do when it legalized hemp in 2018: the tetrahydrocannabinol (THC) found in hemp can get you just as high as the THC found in marijuana.

That finding, in a new study led by researchers at the University of Connecticut, undermines one of the tenets of the 2018 Farm Bill, which made it possible for U.S. farmers to grow hemp again as a cash crop. The thinking at the time was that since hemp contained less than 0.3% tetrahydrocannabinol, the main psychoactive ingredient in marijuana, it couldn’t be used to get high.

The mice found otherwise. When given Delta-8 THC derived from hemp twice a day for five days, the mice showed signs of lethargy, dependence and “liking” behavior. Although not as potent as the Delta-9 THC derived from marijuana, researchers reported in the journal Drug and Alcohol Dependence that Delta-8 had similar psychoactive effects on the mice, “including evidence of dependence and abuse potential.”

“So they’re telling us the same thing people buying the stuff in gas stations tell us: (Delta-8) feels like THC,” says Steve Kinsey, PhD, a UConn School of Nursing professor and director of the Center for Advancement in Managing Pain.

Kinsey and his colleagues say Delta-8 and Delta-9 molecules are similar and act in the same way on the body. But while Delta-9 is illegal under federal law, Delta-8 is legally being sold in a wide array of edibles, beverages, tinctures and other products. Because they are made with CBD and THC derived from hemp, they can be purchased without an ID or marijuana prescription – even in states where medical or recreational marijuana is illegal.  A recent study found that some hemp-based edibles have 360% more THC than those sold in cannabis dispensaries.

“It’s creating a fight between marijuana and hemp” growers, says John Harloe, an attorney on a Colorado taskforce that is trying to address the different chemical variations of THC and their hazy legal status.

“(Marijuana) must be sold through dispensaries and pay high taxes, while hemp producers can sell essentially the same product but without the same regulations, due to the ambiguity in the Farm Bill,” Harloe said in a statement.

The Food and Drug Administration has been slow to regulate CBD products, but earlier this year the agency sent the first warning letters to companies for selling products containing Delta-8. The letters don’t take issue with Delta-8’s legal status, but focus instead on its unauthorized marketing as a treatment for chronic pain, nausea, anxiety and even cancer.

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.

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.

Terpenes Make Cannabis More Effective as Pain Reliever

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

Fibromyalgia Patients Substituting CBD for Pain Medication

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

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

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

Medical Cannabis No Help to Lobsters

By Pat Anson, PNN Editor

Do lobsters feel pain when they’re boiled alive?

Seafood lovers, cooks, academics, animal rights activists and even governments have debated that question for years, with the general consensus being that they do. Lobsters, crabs and other crustaceans will often writhe in pain and try to escape when dropped into a pot of scalding hot water. The practice is considered so cruel that Switzerland and New Zealand made it illegal to boil a live lobster.

Some cooks try to ease the lobsters’ pain by stunning them with a jolt of electricity or putting them on ice to dull their senses before cooking them.  In 2018, a restaurant owner in Maine even blew marijuana smoke on a lobster named Roscoe, who reportedly grew so mellow he never wielded his claws as weapons again while in captivity.

We’ll never know the long-term effect of getting a lobster stoned because Roscoe was returned to the ocean as a thank you for his service. Good for him.

Which brings us to a bizarre study recently completed by scientists at the University of California San Diego and the Scripps Research Institute, who decided to replicate the Roscoe experiment in a lab.

"The 2018 minor media storm about a restaurant owner proposing to expose lobsters to cannabis smoke really was the starting point. There were several testable claims made and I realized we could test those claims. So we did," lead author Michael Taffe, PhD, an adjunct professor at Scripps Research told IFLScience.

Taffe and his colleagues purchased ten Maine lobsters at a local supermarket, fed them a last meal of frozen krill and fish flakes, and placed them in an aerated vapor chamber.

For the next 30 to 60 minutes, the lobsters were exposed to vapor rich in tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis.

Afterwards, some of the lobsters were “rapidly euthanized” with a kitchen shear and dissected, while others were immersed in hot water to see how they’d react.

bioRxiv

Detectable levels of THC were found in the muscles and organs of the euthanized lobsters, so from that standpoint the experiment was a success. But the THC apparently had little effect on the remaining live lobsters, who displayed “distinct motor responses” and other signs of pain when put in hot water.   

"The effect of vapor THC on this nociceptive (pain) behavior was very minimal. Statistically supported in one case, but of very small magnitude," said Taffe.

We’ll leave it to readers to decide whether a study like this is humane, worthwhile or even makes sense. But it is worth noting that taxpayers helped pay for it.

The lobster cannabis study was supported by grants from the U.S. Public Health Service. Researchers were careful to note that federal funding was not directly used to purchase the lobsters. That money came from La Jolla Alcohol Research, a private company that is developing vapor inhalation technologies.  According to GovTribe, La Jolla Alcohol Research has received about $3 million in federal funding in recent years, most of it coming from the National Institute on Drug Abuse.

Cannabis Poisoning Calls Rise, Particularly for Children

By Pat Anson, PNN Editor

A new analysis of calls to U.S. poison control centers suggests that more regulation is needed of cannabis products to protect consumers – and children in particular — from adverse health consequences.

Researchers found a significant increase in cannabis-related calls to poison centers from 2017 to 2019, about half of them from a healthcare facility.

Most of the 28,630 calls involved someone ingesting cannabis flower or buds, but a growing number involved manufactured cannabis products such as edibles, vaporized liquids and concentrates. About a third of the calls were considered serious.

Cannabis-Related Calls to U.S. Poison Control Centers

JAMA NETWORK OPEN

Most of the calls about manufactured cannabis products involved underage children. Twenty-seven percent involved children under the age of 10 and about a third (34.5%) involved youths between 10 and 20 years of age. Edibles were involved in about two-thirds of those calls.

“Children may be at particular risk for exposure to edible products, such as cookies or candy,” wrote lead author Julia Dilley, PhD, Oregon Health Authority, in JAMA Network Open.

“Although we did not see more serious health outcomes for manufactured product exposures compared with plant products overall, most cannabis plant exposures involved polysubstance use, whereas most cases for manufactured products were for those products alone, suggesting that exposure to manufactured products alone may be relatively more likely to generate adverse events.”

Dilley and her colleagues say cannabis products are riskier for children because they may not know they are consuming THC (tetrahydrocannabinol), the psychoactive ingredient in cannabis. Even when they are labeled, research has found that the amount of THC in cannabis products is often inaccurate.

The study did not distinguish between medical and recreational cannabis. Interestingly, the rate of calls to poison centers from states where cannabis is legal was slightly higher than those where cannabis is still illegal, suggesting that legalization does not increase the level of safety.  

“Market factors may drive the industry to continue developing novel products, which could present additional health risks. Applying regulatory controls to market-driven innovations in potency and additives is key. Novice cannabis users are often advised to ‘start low, go slow’; this guidance may be equally applicable to regulating new retail cannabis markets and products,” researchers said.

Some cannabis companies are intentionally marketing their products as candy and snacks to make them more attractive to children. The Food & Wine website reports the Wrigley Company recently filed three lawsuits against cannabis manufacturers, alleging they produced THC-spiked products that resemble Wrigley candies such as Skittles, Life Savers and Starbursts   

“We take great pride in making fun treats that parents can trust giving to their children and children can enjoy safely," a Wrigley spokesperson told Reuters. "We are deeply disturbed to see our trademarked brands being used illegally to sell THC-infused products."

One cannabis company, THC Living, recently took a “snortable” cannabis candy off the market after complaints on social media. According to Leafly, the packaging and marketing of “Cannabis Bumps” were designed to make the powdered candy look like cocaine. Each package contained a hefty dose of 600mg of THC.    

Most Older Adults Don’t Tell Doctors About Their Cannabis Use

By Pat Anson, PNN Editor

A growing number of older adults have discovered the medical benefits of cannabis – everything from pain relief to lower blood pressure. But a new study found that most older Americans aren’t telling their doctors about their cannabis use.

In an analysis of over 17,000 Americans aged 50 and older who participated in the 2018 and 2019 National Surveys on Drug Use and Health, researchers at the University of Texas at Austin found that nearly nine percent had used cannabis in the past year. Of those, less than 40% had discussed their cannabis use with a healthcare provider.

Researchers say that’s an alarming figure because the cannabis users were significantly more likely to have substance abuse and mental health problems than nonusers.  

“Only a minority of older cannabis users discussed their drug use with a healthcare professional, although medical users were more likely than nonmedical users to have done so,” said lead author Namkee Choi, PhD, Professor of Gerontology at the University of Texas at Austin.

“Given little difference in cannabis and other substance use/use disorders between nonmedical and medical users, older cannabis users, regardless of use reasons, should consult healthcare professionals about their use, and healthcare professionals should screen for cannabis and other substance use as part of routine care.”

Compared to recreational users, medical users consumed cannabis more frequently, with nearly 40% using it everyday or a few times each week. Surprisingly, less than 20% of medical users bought their cannabis from a dispensary; most obtained it from friends, family or strangers. About 95% of medical users said obtaining cannabis was fairly easy or very easy.

“The finding that a significant proportion of medical and nonmedical users obtained cannabis via private/informal sources indicates that they are likely to use cannabis and cannabis products with unknown tetrahydrocannabinol (THC) potency,” said Choi. “Given the increase in THC potency, healthcare professionals should educate older cannabis users, especially high-frequency users, on potential safety issues and adverse health effects of cannabis and cannabis products obtained from unregulated sources.”

The study findings were published in The American Journal of Drug and Alcohol Abuse.

A 2018 survey by the American Association of Retired Persons (AARP) found that most older Americans think marijuana is effective for pain relief, anxiety and nausea. Seventy percent of those surveyed say they would consider asking their healthcare provider about medical marijuana if they had a serious condition that they thought might respond to it.

A recent study published in the journal Cannabis and Cannabinoid Research found that older adults are more likely to purchase sublingual formulations of cannabis, such as edibles and tinctures, as well as products low in THC and high in CBD.