What Are Health Risks of Vaping CBD?

By Roger Chriss, PNN Columnist

An outbreak of lung illnesses linked to vaping is raising important questions about the safety of vaping cannabis products. The cause is still unclear, but the CDC reports about 76% percent of the patients who became ill vaped products containing THC – the psychoactive ingredient in cannabis. Only about 17% reported vaping a cannabidiol (CBD) product.

At present, very little is known about CBD vaping safety. The World Health Organization’s 2017 report on cannabidiol looked at oral, sublingual and intranasal routes of administration. When the WHO wrote that “CBD is generally well tolerated with a good safety profile,” it was not considering vaping at all.

The Food and Drug Administration still considers CBD in food and drugs sold commercially to be illegal, unless the product falls under the Food, Drug and Cosmetic Act. Vaping CBD does not, and so there has been no testing or regulatory action.

There have been no good human studies on CBD vaping. Research generally looks at CBD in edibles and liquids, or smoked using traditional means.

It is not known what happens to CBD under vaping temperatures, if there are thermal degradants, or important chemical reactions between CBD and other ingredients in vaping liquids or other drugs.

A recent lung tissue study found concerning results about inhaling CBD while using steroids. CBD helps reduce inflammation, but “acts as an antagonist with steroids, overriding the anti-inflammatory potential of steroids when used in combination.”

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Last year Vice reported on public health warnings in North Carolina after 90 people became sick with headaches, nausea, hallucinations and other health problems after vaping CBD products. Adulterants appear to have been the problem, and Vice noted that vape oils are poorly regulated and sometimes contain chemicals that “when heated in a vape and inhaled, can cause serious lung irritation.”

A recent study on the quality of CBD liquids used in e-cigarettes is also concerning, finding that “the quality control of manufacturers and the relative safety of these products is uncertain.”

An AP investigation last month found that in lab tests on 30 CBD vape products, ten samples contained synthetic marijuana such as K2 or spice, while others had no CBD at all.

Some states with legalized cannabis do require testing of CBD vapes. But it’s not clear what to test for, and even the lab methods for testing have yet to be validated. It is also not known which cutting agents, adulterants and contaminants should be cause for concern. Lung tissue is fragile, vulnerable in ways the GI tract is not, and not well studied. So testing regimes may ultimately require information we currently lack.

Oversight of cannabis testing is limited. California’s Sequoia Analytical Labs was found to be falsifying lab results last year. Plus, many CBD vapes come from the gray or black markets, or are home-brewed, making attempts at quality control irrelevant. As a result, CBD vaping safety is an open question, assuming it is even possible to make a safe CBD vape.

Fortunately, new research may help. Researchers are testing vaporized cannabis extracts on rats. This will allow for studying the effects of THC and CBD in animal models in a way that closely mimics human behavior.

Such information is urgently needed. Animal studies on vaping are raising concerns about lung cancer risk, but such research may not be representative of how humans vape, limiting their value.

There is ongoing debate on what CBD is good for. And now we also have to consider how CBD should be administered. It may be possible to create a low-risk CBD vape product. But at present we don’t really know how to do it.

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Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society.

Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Arthritis Foundation Releases First CBD Guideline

By Pat Anson, PNN Editor

The Arthritis Foundation has become the first major patient advocacy group to release guidelines on the use of cannabidiol (CBD) to treat arthritis pain.  

About 54 million Americans have been diagnosed with arthritis. According to a recent national survey, 79 percent of arthritis patients are currently using CBD, have tried it in the past, or are considering it.

CBD infused products – from edibles to lotions to beverages -- are rapidly going mainstream, even though there is little scientific evidence to support their use. There has also been little guidance for consumers on what products to use or in what doses — until now.

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“We are intrigued by the potential of CBD to help people find pain relief and are on record urging the FDA to expedite the study and regulation of these products,” the Arthritis Ffoundation said in a statement.

“While currently there is limited scientific evidence about CBD’s ability to help ease arthritis symptoms, and no universal quality standards or regulations exist, we have listened to our constituents and consulted with leading experts to develop these general recommendations for adults who are interested in trying CBD.”  

CBD is largely extracted from a hemp, a marijuana strain that has only trace amounts of THC, the active ingredient that makes people high.

"Millions of people in the U.S. are likely trying to use cannabinoids to treat pain, and many are doing this in ways that might cause more harm than good, especially when they use high doses of THC," said Daniel Clauw, MD, a professor of anesthesiology at the University of Michigan who was one of the experts the foundation consulted.

"It's important that the Arthritis Foundation has taken a stand on CBD,” Clauw said in a statement. “Right now, it appears to be fairly safe and might help certain types of pain. It's far better to give this guidance, even if preliminary, because otherwise people will have no guidance whatsoever." 

DRUG POLICY ALLIANCE

DRUG POLICY ALLIANCE

The new guideline is largely cautionary and does not explicitly recommend CBD as a treatment, stating only that it “may help” with arthritis-related symptoms such as pain, insomnia and anxiety.

When taken in moderate doses, experts say CBD has no major safety issues, although it may interact with some drugs commonly taken for arthritis, such as naproxen (Aleve), celecoxib (Celebrex), tramadol (Ultram), gabapentin (Neurontin), pregabalin (Lyrica) and some antidepressants.

The Arthritis Foundation recommends taking CBD in oral sprays or tinctures so the liquid can be taken under the tongue and be absorbed directly into the bloodstream.

Experts say a “go slow” approach is best, starting with a few drops twice a day and increasing the dose gradually over a period of weeks until an effective dose is reached.

The guideline strongly discourages inhaling or vaping CBD because of the risk of respiratory problems. It also discourages taking CBD in edibles, such as gummies and cookies, because the dosing is unreliable. Experts say the effectiveness of topical lotions and creams with CBD is unclear because they often contain other ingredients.

Other key takeaways from the guideline:

  • CBD should never be used to replace disease-modifying drugs that help prevent permanent joint damage in inflammatory types of arthritis.

  • CBD use should be discussed with your doctor in advance, with follow-up evaluations every three months or so.

  • Buy from a reputable CBD company that has each batch tested for purity, potency and safety by an independent laboratory and provides a certificate of analysis.  

Unlike prescription drugs approved by the Food and Drug Administration, the manufacturing process for CBD products is not subject to FDA review, and there has been no FDA evaluation of their effectiveness, proper dosage, how they could interact with drugs, or whether they have side effects. 

The Federal Trade Commission recently warned companies that make CBD products to stop making unsubstantiated claims that cannabidiol can be used to treat arthritis and other chronic pain conditions.

FDA Warns Curaleaf About Marketing of CBD Products

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is warning a large cannabis company to stop making unsubstantiated claims that its products can treat chronic pain, cancer, opioid withdrawal and other medical conditions.

An FDA warning letter was sent to Curaleaf, a Massachusetts-based company that sells cannabidiol (CBD) products online and in stores, and operates dispensaries in a dozen states. CVS Health responded to the FDA letter by pulling some Curaleaf products off its store shelves.

“Selling unapproved products with unsubstantiated therapeutic claims — such as claims that CBD products can treat serious diseases and conditions — can put patients and consumers at risk by leading them to put off important medical care. Additionally, there are many unanswered questions about the science, safety, effectiveness and quality of unapproved products containing CBD,” acting FDA Commissioner Ned Sharpless, MD, said in a statement. “Consumers should beware of purchasing or using any such products.”

Curaleaf, which claims to be the largest cannabis operator in the United States, makes an extensive line of CBD lotions, creams, oils and skin patches.

It recently began marketing a line of CBD products for pets to treat pain, spasms, anxiety and inflammation in animals.

The FDA’s warning letter to Curaleaf cited a number of unapproved marketing claims made by the company online and in social media, including:

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  • “CBD was effective in killing human breast cancer cells.”

  • “CBD has been linked to the effective treatment of Alzheimer’s disease…”

  • “CBD is being adopted more and more as a natural alternative to pharmaceutical-grade treatments for depression and anxiety.”

  • “CBD can also be used in conjunction with opioid medications, and a number of studies have demonstrated that CBD can in fact reduce the severity of opioid-related withdrawal and lessen the buildup of tolerance.”

  • “CBD oil is becoming a popular, all-natural source of relief used to address the symptoms of many common conditions, such as chronic pain, anxiety … ADHD.”

The FDA gave Curaleaf 15 working days to respond. Failure to correct the violations could result in legal action, including seizure of the company’s products.

“Curaleaf is committed to the highest standards of quality and compliance, and will work collaboratively with the FDA to resolve all issues addressed in the agency's letter,” the company said in a statement.

“Compliance is a top priority for Curaleaf and the Company is fully committed to complying with FDA requirements for all of the products that it markets. We can affirm that nothing in the letter raises any issues concerning the quality and consistency of any Curaleaf product or calls into question the high safety standards of the Company's cultivation and manufacturing processes.”

CBD Products Loosely Regulated

Unlike prescription drugs approved by the FDA, the manufacturing process for CBD products is not subject to FDA review, and there has been no FDA evaluation of their effectiveness, proper dosage, how they could interact with drugs, or whether they have side effects.

Despite the lack of regulatory oversight, there has been explosive growth for CBD companies and their products are starting to appear in mainstream stores. In March, CVS Pharmacy and Walgreens started selling CBD lotions, tinctures, edibles and lozenges — including some made by Curaleaf.

“The only Curaleaf products we are selling are its CBD lotion and CBD transdermal patches,” CVS said in a statement. “Following the FDA’s warning letter to Curaleaf, we will be removing these items from our CBD offering.”  

The FDA sent similar warning letters to three cannabis operators in April. Until now, the enforcement actions have been sporadic and only targeted small companies.

“We will continue to work to protect the health and safety of American consumers from products that are being marketed in violation of the law through actions like those the FDA is taking today. At the same time, we also recognize the potential opportunities and significant interest in drug and other consumer products containing CBD,” said FDA Principal Deputy Commissioner Amy Abernethy, MD.

“We understand this is an important national issue with public health impact and of interest to American hemp farmers and many other stakeholders. The agency has a well-established pathway for drug development and drug approvals, and we remain committed to evaluating the agency’s regulatory policies related to other types of CBD products.”

The FDA held a public hearing on the issue in May, and opened a docket for public comments to obtain scientific data about the safety, manufacturing, quality, marketing, labeling and sale of CBD products. Nearly 4,500 comments were received. The agency plans to report on its progress this fall.

This week Curaleaf announced it will acquire GR Companies, a large cannabis retailer, in a cash and stock deal valued at $875 million. Curaleaf said the purchase solidifies it’s position as “the world's largest cannabis company by revenue and the largest in the U.S. across key operating metrics.”

The Future of CBD

By Roger Chriss, PNN Columnist

Is CBD a medical miracle or just another over-hyped health fad? The cannabinoid known as cannabidiol (CBD) is appearing in hundreds of foods, drinks and health products – even though we know little about its potential harms and benefits. Recent research runs the gamut, suggesting that CBD can fight superbug infections or cause liver damage.

A review of 35 clinical studies found CBD effective in treating anxiety and epilepsy, but there was no evidence it works for diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain.

But there may be some untapped possibilities. Ingenious bench science and clinical research is improving our understanding of how CBD acts in the body, which is leading to new drugs with impressive potential for treating serious illnesses.

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How Does CBD Work?

In simple terms, no one knows. CBD doesn’t seem to act directly on the cannabinoid receptors CB1 and CB2, although it does have some activity in serotonin 5HT1A, GRP55, and TRPV1 receptors that regulate anxiety, inflammation and pain sensation.  

Although none of these receptors is directly involved in seizures, CBD is being used successfully to treat epilepsy and other seizure disorders. CBD in the highly-purified form Epidiolex is FDA-approved as “add-on therapy” for Dravet syndrome and Lennox-Gastaut syndrome, two rare childhood seizure disorders.

New pharmacological research suggests that CBD may reduce seizure frequency through a “drug-drug interaction” rather than as an anti-seizure medication in and of itself.

In other words, whatever CBD is doing probably involves a host of small nudges often described as endocannabinoid activity. This makes for a complex set of interactions and contraindications, many still not well understood.  

New Drugs Derived from CBD

CBD acts on too many receptors in too many ways to make for predictable clinical effects. And at high doses CBD is potentially toxic to both the liver and nerves over the long term. But understanding this activity is helping guide research.

A potent CBD-derived compound called KLS-13019 has a more targeted effect on receptors and is being studied as a treatment for some neurological conditions.

Even more promising is EHP-101, an oral formulation of a synthetic CBD molecule that helped repair myelin around damaged nerve fibers in mice. This is an exciting if preliminary finding that may have potential for treating multiple sclerosis (MS). Emerald Health Therapeutics is planning to launch a Phase II clinical trial of EHP-101 in MS patients by the end of the year.

“Restoring the myelin sheath around nerves, or remyelination, would be considered a ‘Holy Grail’ outcome in the treatment of MS,” Jim DeMesa, MD, CEO of Emerald Health Pharmaceuticals, said in a statement. “These preclinical data provide the first evidence of remyelination with our lead clinical-stage drug product candidate and provide promising evidence for the possibility to treat, and potentially reverse, several forms of MS in the future.”

CBD itself may have uses as a wellness product for otherwise healthy people. It is certainly an appealing indulgence. But CBD-derived products that avoid the complications of CBD while taking advantage of specific activity learned from studying CBD are showing great promise.

New drugs replace old drugs all the time. Aspirin was outclassed by ibuprofen and naproxen, barbiturates by benzodiazepines, and MAO inhibitors by TCAs and more recently SSRIs. CBD may fade as a pharmaceutical, but its descendants could be the wonder drugs that CBD is often touted as.

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

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Is CBD Psychoactive?

By Roger Chriss, PNN Columnist

The CBD boom is making Dutch Tulip Mania seem dull. CBD water is becoming a thing, and Ben & Jerry’s may soon introduce a CBD-infused ice cream. Basically, CBD is in everything.

The boom is built on the assumption that CBD, the cannabis cannabinoid known as cannabidiol, is not psychoactive. The FDA isn’t so sure and the DEA demurs, putting the CBD-based seizure drug Epidiolex into Schedule V last year.

So is CBD psychoactive? The answer hinges on the definition of the term psychoactive.

According to the World Health Organization: "Psychoactive substances are substances that, when taken in or administered into one's system, affect mental processes, e.g. cognition or affect.”

The National Institute on Drug Abuse explains psychoactive drugs this way: “Drugs in this category act on the central nervous system and alter its normal, everyday activity, causing changes in mood, awareness, and behavior.”

The term “psychotropic” is used with a similar meaning. MedicineNet states that a psychotropic drug is “any drug capable of affecting the mind, emotions, and behavior.”

But does CBD affect mental states, alter everyday activity, or change mood, awareness, or behavior?

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The FDA last year approved Epidiolex -- the first CBD-based medication -- for the treatment of two rare and severe forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. CBD potentially has many other uses, including neurological conditions such as Alzheimer’s and dementia, and neuropsychiatric illness such as autism, ADHD, and PTSD.  It could also be beneficial for anorexia, anxiety, and mood disorders.

Purveyors of commercial CBD products go further, claiming that CBD may help with insomnia, social anxiety, and panic attacks. Although most product labels avoid specific claims of treatment efficacy to avoid FDA scrutiny, clear statements of possible benefits are easy to find online.

The FDA recently sent a warning letter to a New Jersey company for claiming that CBD can treat anxiety, depression, PTSD, schizophrenia, psychosis and obsessive compulsive disorder.

In order for CBD to do even half of this, it would have to have an effect on mental states, mood and awareness. In other words, CBD could not do what its proponents claim without being psychoactive, at least in the narrow, technical sense of the term.

Dose Matters

But details matter here. First, psychoactive does not mean intoxicating, hallucinogenic or dissociative. And many prescription drugs have benefits precisely because they are psychoactive. Even caffeine is arguably psychoactive, though only very weakly.

Second, dose matters. The pharmaceutical Epidiolex is administered in doses that have 10 to 100 times more CBD than a typical over-the-counter or commercial CBD product. So CBD may be psychoactive in therapeutic doses, but not in “commercial” doses. Of course, this assumes the product actually contains CBD, which in practice is not necessarily the case.

Third, route of administration matters. CBD is only weakly bioavailable and unstable in light or temperature extremes. A clear bottle of CBD water or CBD bath oil could easily lose much of the CBD it may contain, and the remaining CBD may not even be absorbed. And if the CBD is applied to non-vascularized tissue, as is the case with CBD mascara, then it cannot be psychoactive because of a lack of blood vessels for transport to the brain.

Thus, whether or not CBD is psychoactive depends on the amount and method that CBD is introduced to the human body. Since most of the claims from proponents remain unverified and in many cases untested even in animals, it could be premature to state that CBD is psychoactive in a specific way.

On the other hand, the existing work on CBD argues for calling CBD psychoactive. Recent findings by Yasmin Hurd showed that CBD, specifically Epidiolex, reduces cravings in people addicted to heroin. Ongoing research is demonstrating possible benefits of CBD for seizure disorders in humans and even in dogs.

Project CBD noted in 2016 that “as our scientific understanding and therapeutic experience deepens, the description of CBD as non-psychoactive may fall by the wayside.”

For now, it would be reasonable to say that CBD is probably “weakly psychoactive” at commercial doses but more “strongly psychoactive” at therapeutic doses. As more studies are completed on what CBD actually does, the pharmacological description of CBD can be updated accordingly.

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

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Feds Warn CBD Marketers About False Medical Claims

By Pat Anson, PNN Editor.

The Food and Drug Administration and the Federal Trade Commission are tapping the brakes on the fast growing market for cannabidiol (CBD), warning companies not to make false claims that CBD products can be used to treat fibromyalgia, migraine, arthritis and other chronic illnesses.

The agencies sent warning letters to three companies — Nutra Pure, PotNetwork Holdings, and Advanced Spine and Pain — for making false and unsubstantiated health claims about a variety of CBD oils, extracts and edibles.

The FDA and FTC sent the warning letters on March 28 and gave the companies 15 days to respond.

Nutra Pure’s website, according to regulators, claimed that “CBD has demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms responsible for the pain associated with migraines, fibromyalgia, IBS and other related disorders.”

Claims were also made that CBD is “an effective and safe treatment alternative” for inflammatory conditions such as lupus, Celiac disease and rheumatoid arthritis.

Nutra Pure, which makes a line of hemp oil, has a small disclaimer on its website stating that “these products are not intended to diagnose, prevent, treat, or cure any disease.”

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NUTRA PURE IMAGE

PotNetwork has a similar disclaimer on its website, where it sells everything from CBD infused gummy bears and energy drinks to moisturizers and pet care products. According to the FDA, the company falsely claimed that CBD “blocked the progression of arthritis” and “has also shown the ability to kill cancer cells directly.”  

In addition to marketing CBD products, Advanced Spine and Pain also offers stem cell therapy, steroid injections, trigger point injections and ketamine infusions at its “Relievus” clinics in New Jersey and Pennsylvania.

‘Open Questions’ About CBD Safety

The federal crackdown on CBD marketing comes at a time when CBD products are starting to appear in mainstream stores. CVS Pharmacy and Walgreens started selling cannabis-based lotions, tinctures, edibles and lozenges in stores last month. The CBD products are being sold over-the-counter and without a prescription.  

The FDA and FTC announced no actions against CVS, Walgreens or other retailers selling CBD products, but they sent a clear message that the marketing of CBD will be closely watched.

“We treat products containing cannabis or cannabis-derived compounds as we do any other FDA-regulated products. Among other things, the FDA requires a cannabis product (hemp-derived or otherwise) that’s marketed with a claim of therapeutic benefit to be approved by the FDA for its intended use before it may be introduced into interstate commerce,” FDA commissioner Scott Gottlieb, MD, said in a statement. “Additionally, it is unlawful to introduce food containing added CBD, or the psychoactive compound THC, into interstate commerce, or to market CBD or THC products as dietary supplements.”

The 2018 Farm Bill removed hemp – a less potent strain of marijuana – from the Controlled Substances Act. That made hemp products legal to sell, but left the FDA in charge of regulating dietary supplements containing CBD. The agency is still trying to figure out how to regulate a product for which there is growing consumer demand, but little scientific evidence to support its use.

“While the availability of CBD products in particular has increased dramatically in recent years, open questions remain regarding the safety considerations raised by their widespread use,” Gottlieb said. “There are also unresolved questions regarding the cumulative exposure to CBD if people access it across a broad range of consumer products, as well as questions regarding the intended functionality of CBD in such products.”

Gottlieb has announced plans to hold a public hearing on May 31 to review the safety and effectiveness of CBD products. The FDA is also forming an internal working group within the agency to explore what regulatory changes would be needed for CBD products to be marketed legally.  

Study: THC More Effective Than CBD in Treating Pain

By Pat Anson, PNN Editor

The psychoactive ingredient in marijuana -- tetrahydrocannabinol (THC) – is more effective than cannabidiol (CBD) in treating chronic pain and other medical conditions, according to a new study that challenges the widespread belief that THC is harmful and has limited value in medical cannabis products.

Researchers at the University of New Mexico used the Releaf App, a mobile software program, to analyze self-reported data from over 3,300 people who logged their responses in nearly 20,000 user sessions to a variety of cannabis products, including natural dried flower, edibles, tinctures and ointments.

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Dried flower was the most commonly used product and was generally associated with greater pain relief than other cannabis products, regardless of the amount of THC.

"Despite the conventional wisdom, both in the popular press and much of the scientific community that only CBD has medical benefits while THC merely makes one high, our results suggest that THC may be more important than CBD in generating therapeutic benefits,” said Jacob Miguel Vigil, PhD, a professor in UNM’s Department of Psychology.

“In our study, CBD appears to have little effect at all, while THC generates measurable improvements in symptom relief. These findings justify the immediate de-scheduling of all types of cannabis, in addition to hemp, so that cannabis with THC can be more widely accessible for pharmaceutical use by the general public.”

Hemp is a strain of marijuana that was legalized by Congress in the 2018 Farm Bill. It has very low levels of THC, but is being grown commercially as a source for CBD.

UNM researchers found that indica strains of cannabis were more effective than sativa strains in treating pain and insomnia. Both strains have substantially higher levels of THC than hemp, but are illegal Schedule I controlled substances under federal law.

“Only THC potency levels showed independent associations with symptom relief and experiences of both positive and negative side effects, with higher levels (of THC) resulting in larger effects,” Vigil said.

Researchers say the relative weakness of CBD in treating symptoms may be due to inaccurate labeling of CBD content in cannabis products, which is a widespread industry problem. It’s also possible that THC simply heightens the experience or awareness of symptom relief.

Vigil published his findings in the journal Scientific Reports. Three of his co-authors developed the Releaf App, which has collected information from cannabis users since 2016. The app is an important data source for researchers, who are currently limited in conducting clinical studies of cannabis because of federal regulations.

Two previous studies by Vigil using data from the Releaf App found that cannabis provides significant relief from a wide range of symptoms associated with chronic pain, including insomnia, seizures, depression, anxiety and fatigue.