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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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.  

CVS Begins Selling Cannabis Products

By Pat Anson, PNN Editor

You may not be able to get your opioid prescription filled at a CVS pharmacy, but you can stock up on medical marijuana. The nation’s largest drug store chain has begun selling cannabis-based products in eight states, despite lingering concerns about their effectiveness and legal status.

The move was announced by cannabis retailer Curaleaf Holdings, which carries a line of cannabis lotions, tinctures, edibles and lozenges that CVS started carrying in its stores last week. The CBD products are being sold over-the-counter without a prescription.

(Update: Walgreens has also announced plans to sell CBD products in 1,500 of its stores.)

CBD stands for cannabidiol, a chemical compound in marijuana that does not produce euphoria but is believed to reduce symptoms of chronic pain and other health conditions.  

“We have partnered with CBD product manufacturers that are complying with applicable laws and that meet CVS’s high standards for quality,” a CVS spokesman said in an email to MarketWatch.  

CVS said that it was selling CBD products in Alabama, California, Colorado, Illinois, Indiana, Kentucky, Maryland and Tennessee. Curaleaf executives said CVS would eventually carry its products in 800 stores in ten states.

“We’re going to walk slowly, but this is something we think our customers will be looking for,” CVS Health CEO Larry Merlo told CNBC.

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‘Treated Like Criminal’ at CVS

The move is somewhat puzzling for CVS, which was one of the first pharmacy chains to crackdown on opioid prescriptions due to concerns about addiction and overdose. In 2017, CVS began restricting initial opioid prescriptions to 7 days’ supply and aligned its polices with the CDC opioid guideline.

Pain sufferers now complain they’re treated like drug addicts by CVS pharmacists.

“I submit to monthly drug tests and do everything I am supposed to do and I am treated like a criminal at the doctor and CVS pharmacy. My two pills a day barely touches the pain, but I need to work,” one patient recently told us.

“Some pharmacies, such as CVS, have taken it upon themselves to deny my prescriptions that I have been having filled there for 15 years. They first took it upon themselves to adjust my dosage. I didn’t realize that pharmacist were allowed to change a prescription,” said another patient.

“Why does CVS, a drug store that sells NSAIDs without restriction, have control of how I treat my patient?” asked one practitioner.

Although most Americans now support the use of medical marijuana and it is legal in dozens of states, the safety, effectiveness and legality of CBD is still very much up in the air.  Marijuana remains classified as a Schedule I controlled substance by the DEA, alongside heroin and LSD.

“Societies have jumped far, far ahead of science,” Dr. Margaret Haney, a professor of neurobiology at Columbia University Medical Center, told NBC News. “So it’s showing up in lotions and pretty much any form of product one can use. There’s a lot of different ways one could use CBD, but the ways we have studied CBD is much more limited.”

According to MarketWatch, Curaleaf only list its shares on the Canadian Securities Exchange because major exchanges in the U.S. and Canada will not list shares of marijuana companies due to their hazy legal status.

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.

CBD Is Now Regulated and That May Be a Good Thing

By Roger Chriss, PNN Columnist

The legal status of cannabidiol (CBD) is changing. Once classified exclusively as a Schedule I drug under the Controlled Substances Act, CBD is now legal under federal law. And this means regulation.

The 2018 Farm Bill removed hemp from Schedule I. Hemp is a strain of marijuana with very low levels of THC, but high amounts of CBD.  This has opened the door to a legal market for CBD products, including food and supplements. But there’s a catch. The FDA has strict regulations about CBD being used in dietary supplements or promoted as medical treatments.

“It’s unlawful under the FD&C Act (Federal Food, Drug, and Cosmetic Act) to introduce food containing added CBD or THC into interstate commerce, or to market CBD or THC products as, or in, dietary supplements, regardless of whether the substances are hemp-derived,” FDA commissioner Scott Gottlieb, MD, said in a December 2018 statement.

“Among other things, the FDA requires a cannabis product (hemp-derived or otherwise) that is marketed with a claim of therapeutic benefit, or with any other disease claim, to be approved by the FDA for its intended use before it may be introduced into interstate commerce. This is the same standard to which we hold any product marketed as a drug for human or animal use.”

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 The FDA has a FAQ page about cannabis that answers some basic questions:

"Can products that contain THC or cannabidiol (CBD) be sold as dietary supplements? A. No."

"Is it legal, in interstate commerce, to sell a food to which THC or CBD has been added? A. No."

The FDA has reason to be concerned. Product quality for CBD products is iffy at best. An investigation by the NBC affiliate in Miami (see “Patients Are Being Duped”) found that 20 of 35 CBD products tested had less than half the amount of CBD advertised on the label. Some samples had no CBD at all.

Other recent analyses have found THC, pesticides, synthetic cannabinoids and toxic solvents in CBD products.

Moreover, a lack of regulatory oversight has led to an abundance of false, misleading or unsubstantiated claims. A recent review of CBD in the Journal of Clinical Pharmacology found that “CBD has been touted for many ailments for which it has not been studied, and in those diseases with evaluable human data, it generally has weak or very weak evidence.”

There is a lot of research on CBD going back years. The FDA’s approval of the CBD-based drug Epidiolex for rare childhood seizure disorders and a 2018 review that found potential for treating multiple sclerosis symptoms are important indicators of CBD’s medical value. At the same time, researchers have found no benefit in treating spinal cord injury, Crohn’s disease and osteoarthritis.

Yet CBD is now being widely promoted as a wellness product, and added to everything from coffee and pastries to bath oils and mascara. So it is not surprising that the FDA is concerned that people may be duped or put at risk.

The FDA is not alone in this. The New York City Department of Health has banned CBD products from being sold in bars and restaurants. Maine, New York, and Ohio are also banning CBD edibles.

For medically complicated people with chronic illness, regulation could be beneficial. At present these patients face significant risks with CBD products. Tainted CBD may cause unexpected allergic reactions or drug interactions. And contaminated CBD could trigger a positive result on a urine drug test, a common part of pain management amid the opioid crisis. Regulatory oversight could help reduce these risks. 

The legal and regulatory landscape surrounding CBD is shifting quickly. The FDA and state government agencies are watching closely and starting to intervene. This may flush out bad actors in the CBD marketplace and improve product quality and reliability. A stable marketplace with reliable products may be a net gain for the people who stand to benefit the most from CBD.

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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.