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The best – and worst of CBD oil

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Constance Finley was an entrepreneur who traveled extensively for her own company making investments in low-income housing projects. By the time she turned 40, her health had started to decline, and she began having difficulty using her hands and arms.

Following shoulder surgery, suddenly both of her arms became unusable, and she had to stop working. Soon she was an invalid, locked in her California home. For 15 years, she only went outside for doctors’ appointments.

“For 10 years I didn’t have a diagnosis, which is very often the case with chronic diseases,” she says. “I was finally diagnosed with a severe form of ankylosing spondylitis with cubital tunnel syndrome on both sides.”

Ankylosing spondylitis is a form of arthritis primarily affecting the spine, and cubital tunnel syndrome is a condition that involves the ulnar nerve in the wrist, causing numbness or tingling in the fourth and fifth fingers, pain in the forearm, and weakness in the hand.

The drugs the doctors put her on, including the rheumatoid arthritis drug Humera, produced severe reactions and did nothing to alleviate her symptoms.

After a drug reaction that almost killed her, she reluctantly turned to medicinal cannabis as a last resort because it was legal in California, and after her near-death experience, her doctors refused to prescribe more prescription drugs. Much to her surprise, she found using medical cannabis to be “extraordinarily effective.”

A trained chef with a graduate degree in clinical psychology and a fierce desire to get well, Finley turned her basement wine cellar into a private laboratory so she could experiment with cannabis and find out how to make it more medically potent.

She was also intrigued by cannabidiol, or CBD, a molecule discovered in 1940 that accounts for up to 40 percent of the hemp plant’s extract. CBD is a cannabinoid – the family of compounds found in cannabis – but unlike the cannabinoid THC (delta-9-tetrahydrocannabinol), it was not linked to the “high” of cannabis.

She wondered, “What if we could get similar effects with CBD, without the psychoactive euphoria from THC?”

An early pioneer in CBD extraction, Finley soon found that CBD was extremely helpful for her symptoms in combination with THC, and that it was also helpful for many conditions by itself. In particular, CBD helped tremendously with the neuropathic pain she was experiencing, and it also helped reduce her sense of anxiety.

She also needed the THC, however, because of the severe inflammation. “CBD and THC work on different pathways in inflammation,” she says, “and when they are combined, it is the most powerful of all.”

Vastly encouraged with her own healing progress, she put her entrepreneurial hat back on (now that she could use her arms and hands again), and San Francisco-based Constance Therapeutics was born, a company that specializes in producing cannabis extracts with high cannabinoid content.

The wild, wild west
As species of cannabis, both hemp and marijuana contain cannabinoids – a class of chemical compounds that act on the cannabinoid receptors in the brain, where they affect neurotransmitter release. CBD is found in both marijuana and hemp.

Today, the majority of commercial CBD products are derived from the hemp plant, because hemp is high in CBD and low in THC, which causes the euphoric high associated with marijuana. CBD from industrial hemp, which is defined as containing less than 0.3 percent THC, has been removed from the Controlled Substances Act in the US and is legal at 0.2 percent THC content in the UK.

With the steady legalization of medical marijuana and the growing number of positive studies on the symptom-reducing and healing effects of CBD, the market for CBD products – oils, soft gels, topical creams and lotions – has exploded.

Today we’re being flooded with CBD products, from CBD-enhanced toothpaste and hair products to CBD suppositories, potato chips, hand sanitizer, tampons, CBD-impregnated socks, even CBD toilet paper.

CBD oil has even become a popular additive to smoothies and morning coffee. It’s all part of the profitable CBD market, which has a compound annual growth rate of over 38 percent and is expected to surpass $3.5 billion annually by the year 2024.

“It is really the wild wild West,” says Dr Michael D. Lewis, an expert on CBD, brain health and the prevention, management and rehabilitation of concussions and traumatic brain injury. “Technically, CBD is not a dietary or nutritional supplement, but essentially in the US that’s the model it’s being sold under.

“You can buy a glucosamine product, and you don’t even know if there’s any glucosamine in it. It could be flour in a capsule. You have no idea, because FDA oversight in the US is about safety. If it’s not going to hurt anybody, the FDA really doesn’t regulate it, and it doesn’t regulate CBD oils being sold as health supplements. This means you don’t know what you’re getting. You don’t know if the quality is going to be something that is going to be effective, number one, and it may even be harmful.”

The same unregulated situation exists in the UK. Hemp-based CBD with less than 0.2 percent THC is legal as a food supplement, so you can go to a health food shop or online and get a CBD product without a doctor’s involvement.

Buyer beware
The lack of regulation is a major issue for the industry. “It causes a big problem for the consumer,” says Professor Michael Barnes, a neurologist and rehabilitation medicine specialist and founder of the Medical Cannabis Clinicians Society in the UK. “There’s a lot of media attention on CBD and its medical uses, but you can’t get medical-grade CBD (containing THC) except privately through doctors writing a prescription. And medical CBD with THC is expensive.

“So, quite rightly, people are going through food shops and getting CBD over the counter. Unfortunately, this is not particularly good because of the highly variable quality. And the manufacturers can’t make any medical claims for something that’s not registered as a medicine. So, there’s a lot of confusion.

“Every day I have people asking me, ‘I got this product at the food shop, how much should I take for my whatever-it-is problem?’ And I don’t have an answer because there’s no knowing what kind of product the person really has.”

Dosages for over-the-counter CBD products are another issue. Most CBD products on the market average a CBD dose of somewhere from 5 to 25 mg. And yet, according to Finley, most people knowledgeable about CBD believe that’s a placebo or, at best, a low maintenance dose.

“Take for example using CBD as a sleep aid,” she says. “People say that CBD helps them get more sleep, but research shows that it takes at least 1,800 mg of CBD before it is sleep inducing. But if they’re anxious and they take CBD, they will feel less anxious and thus sleep will be easier. If they have certain kinds of pain or certain spasticity or if they are depressed, they will have those symptoms relieved. So, then they’re able to sleep.

“In general, what people have done is they’ve taken THC dosing and applied it to CBD without any evidence that that is necessary or correct. Dosing should be considered more scientifically than it is.”

People are also confused about the difference between THC and CBD, how they work and which is good for a particular condition.

Topical vs ingestible
Dr Michael D. Lewis, an expert on CBD and brain health, says topical application of CBD creams, oils and ointments can be great for localized pain such as tennis elbow and joint pain. “It’s also excellent for skin issues like eczema
and psoriasis and things like that because they’re inflammatory diseases.”

Although some people are concerned about using CBD topically, thinking it will affect them systemically, Lewis says that’s not really a concern. But topical application has the great advantage of being extremely quick to have an effect. Many people experience relief from pain in a matter of seconds.

Whether it’s capsules or softgels, sprays, drops or tinctures, ingestible CBD has a much slower onset because you have to digest it. For quickest delivery, he recommends putting drops on your tongue.

“CBD ingestibles may take 20 or 30 minutes to help,” he says. “But compare that to an SSRI prescription drug that will take 20 to 30 days to kick in. I’ve seen it work that quickly, especially with anxiety. There’s a reason raw hemp oil has the nickname ‘nature’s ibuprofen.'”

When working with a patient with chronic pain, especially joint pain, Lewis says he attacks it topically to help locally with the nerves and inflammatory mediators. He also has patients ingest raw hemp oil softgels, which help with both pain and inflammation.

How should I choose a CBD oil?
In the UK, Professor Michael Barnes says the only way you can tell if an over-the-counter CBD product has been made to a high standard is if it meets good manufacturing practice (GMP) guidelines.

He recommends calling or writing to a manufacturer and asking for a certificate of analysis, which will list the contents of the product. “Otherwise, find a product that says clearly on the label how many milligrams of CBD it contains per drop or per milligram, per spray or whatever unit of dosing they’re using, as well as a listing of whatever else is in it.”

In the US, Dr Michael Lewis advises researching the industry leaders. “Choose companies that have had a product line for more than 20 minutes,” he says, “companies you can you reach out to and get a third-party independent analysis of the product by lot number.”

Lewis says that only a handful of companies have been around for very long. The industry leaders include CV Sciences and Charlotte’s Web, now called CW Hemp.

The cannabinoid system
The human body has an in-built (endogenous) cannabinoid system, which means that it can produce cannabinoids on its own (called endocannabinoids), along with producing two cannabinoid receptors, called CB1 and CB2, that bind to cannabinoid molecules.

Most CB1 receptors are located in the brain and appear to affect cognitive function. CB2 receptors, on the other hand, are mostly found in the immune system. This makes them more responsible for the body’s response to pain and inflammation.

THC mainly attaches to the CB1 receptors, producing the psychoactive euphoric “high” of cannabis. CBD, on the other hand, does not bind strongly to either receptor. Instead, it interacts with other molecular pathways, such as to activate serotonin receptors and encourage higher levels of endocannabinoids like anandamide.

“Our own body makes cannabinoids,” says Lewis. “Our bodies are really meant for these made-on-demand chemicals, and anandamide is literally our ‘happy molecule.'”

Anandamide is a neurotransmitter named after the Sanskrit “ananda,” which means “joy, bliss and delight.” As it turns out, CBD inhibits the enzyme in our bodies that breaks down anandamide, thereby increasing its short lifespan in our bodies.

CBD is generally considered to be “non-psychoactive,” meaning it has no effects on people’s state of mind. However, Finley’s research has led her to believe that is not actually true. “People say that CBD isn’t psychoactive and that THC is,” she says. “But the truth is, THC is euphoria-producing and CBD is focus-producing. It’s just that it’s an effect most people want, and it doesn’t produce disorientation. CBD is incredibly powerful for ADD and bipolar conditions, anxiety and all those kinds of issues.”

According to Finley, CBD and THC both work on different pathways involved in inflammation. For severe chronic inflammation, she says, a combination of the two is most effective. Low doses of THC can also be highly effective for the shaking symptoms that accompany Parkinson’s disease. But CBD, she says, is “miraculous” for relieving other Parkinson’s disease symptoms, such as muscular rigidity and impaired balance and posture.

“CBD is neuro-regenerative,” she says, “so it can actually rebuild neural pathways. We’ve worked so far with 5,500 people who were out of options, who were referred by their doctors because they were looking for something that regular medicine couldn’t give them.

“With CBD, what we saw is pretty much miraculous results with people suffering from neurodegenerative diseases such as Huntington’s and Parkinson’s. In as little as two or three days it brought them some comfort from symptoms.”

The entourage effect
In our reductionist culture, we tend to look for the “magic bullet.” We single out one compound or molecule from plants such as cannabis, and think, “That’s it!” This has very much been the case with CBD. Cannabis and hemp are known to contain 113 cannabinoids. So far, medical science has only investigated a handful, including CBD, THC and, to a lesser degree, CBG (cannabigerol) and CBN (cannabinol).

In addition, cannabis and hemp contain over 200 terpenes (aromatic oils) and many different flavonoids (plant pigments). “All the current cutting-edge research suggests that it’s the synergy of all these things that’s important,” says Constance Finley, founder of Constance Therapeutics in San Francisco. “Until we know which of the over 500 compounds are the most important, why would we try to be smarter than the plant? What’s the research on taking CBN without all the other aspects of the plant over time?”

Both Barnes and Lewis agree and mention that a full-on “pure” extract CBD oil misses out on what is known as the entourage effect. “None of the individual cannabinoids have medicinal broad-spectrum properties,” says Lewis. “Even just a trace amount of THC can actually make CBD more effective. The reality is, the entourage effect of the broad spectrum of all of these things together – cannabinoids, terpenes, flavonoids – makes it more effective. And you need lower doses. Doing so widens the safety profile tremendously.”

Health breakthroughs
Ever since the story of Charlotte Figi from Colorado broke in 2011, one of the most famous applications for CBD oil has been in treating epilepsy, especially in children.

Charlotte began having seizures at three months old, and by the time she was five, she was having 300 grand mal seizures a week. Often her heart would stop, and her mother would have to do CPR. Eventually, she was diagnosed with Dravet syndrome, a rare and untreatable form of epilepsy that cannot be controlled by medication.

Unable to function, all normal childhood development ceased, and doctors recommended placing Charlotte in a medically induced coma to give her body a chance to rest and recuperate. In desperation, her terrified parents turned to marijuana, illegally purchasing a couple ounces of cannabis bred to be high in CBD and low in THC and paying for the oil to be extracted. After the very first dose, Charlotte’s seizures stopped.

Her parents continued to give her the CBD oil twice a day in her food and were shocked that she had no seizures for a whole week. By the age of six when her story first made headlines, Charlotte was still taking CBD oil twice a day, and was otherwise a normal thriving little girl. She only had seizures two to three times per month, almost always at night in h
er sleep.

Since Charlotte’s case, the US Food and Drug Administration (FDA) has approved Epidiolex, a prescription form of CBD, for this rare form of epilepsy.

Green horizons
Recent studies confirm that CBD reduces the number of seizures – not just in Dravet syndrome but in all types of epilepsy in both children and adults – by an average of 50 percent.1 It also has other seemingly calming effects on the brain. For example, CBD can improve symptoms of generalized anxiety and some sleep disorders,2 and when people with Parkinson’s disease were put in a stressful situation (giving a speech), CBD reduced their anxiety and the strength of their tremors compared to placebo.3

In addition to anxiety disorders, the biochemical properties of cannabinoids suggest that CBD could be used as a treatment for bipolar disorder and for curbing addictions.4 It’s also helped people with PTSD, particularly those with frequent nightmares, reduce their symptoms.5

CBD has been shown to reduce chronic neuropathic pain, as well as pain caused by rheumatoid arthritis.6 And although there hasn’t been a clinical trial of CBD for osteoarthritis in humans yet, CBD has been shown to relieve pain, inflammation, peripheral nerve damage and other symptoms of osteoarthritis in rats.7

In cancer patients, cannabinoids are used to relieve pain and nausea and improve appetite. But beyond helping with symptoms, they may be cancer-fighting themselves (see page 60, “Best supplements for cancer”). Laboratory studies have revealed antitumor effects in several types of cancer, although these haven’t yet been replicated in humans.8

CBD also appears to have effects on the vascular system, as it has been shown to reduce blood pressure and heart rate in rats put under stressful circumstances, and to increase cerebral blood flow in mouse models of stroke.9

Additionally, CBD is being studied as a potential new approach for mitigating irritable bowel disease – it’s proven effective in animal studies as well as anecdotally for patients.10

Dr Adam Abodeely, a board-certified surgeon and chairman of the Dispensary Review Committee for the Association of Cannabis Specialists in the US, says he’s had several patients who have been able to decrease or stop medications for a variety of gastrointestinal conditions including inflammatory bowel and irritable bowel syndrome (IBS) by supplementing with cannabinoid-based therapy.

He says it’s equally effective for many other conditions. “I had one lady write me that she was ready to have her leg amputated because she was in such bad pain,” he says. “She was on opioids and didn’t want to continue with those anymore and was literally ready for them to take her leg. She started CBD therapy with one of my formulas, and now she can walk again and is pain-free.

“I also had an 80-year-old farmer who was completely disabled, couldn’t ride his tractor anymore. He started on CBD oil, and now he’s back on his tractor.”

How is it possible that CBD can have such wide-ranging effects? “Underlying all these conditions is inflammation, and that’s the connecting piece,” says Lewis. “That’s how CBD can impact all these things. Is it a cure? No, absolutely not. But if you decrease inflammation consistently and effectively, you can definitely impact these different disease processes.”

How much do I take?
For back pain or pain in general, Professor Michael Barnes, MD, founder and president of the World Federation of Neurological Rehabilitation, recommends taking between 60 and 100 mg CBD daily by mouth, split into two doses. (It’s easiest to use an eyedropper or a 1-milligram syringe to measure the dose.)

The best rule of thumb, however, is to “Start low and go slow,” he says.

“About 10 percent of the population are quite sensitive, and they metabolize CBD quite slowly,” he says. “So start with say 10 mg a day for four or five days or a week – whatever is easiest to keep track of – and then move it up to 20 and then 30 and 40 milligrams until you get to what is for you the most efficacious dose.” (It varies with every person.)

Barnes says that if you haven’t gotten a proper response with about 150 to 200 mg daily of CBD, chances are you’re not going to get one. At that point, he recommends thinking about using a CBD product with added THC.

Nevertheless, there is no real upper limit for CBD dosage. According to Constance Finley, founder of Constance Therapeutics in San Francisco, there have been no studies that show CBD ingestion to be harmful. “It’s plant-based medicine,” she says. “In the instance of CBD, we can’t find that it does any permanent harm.”

She adds the important and little-known or understood point that CBD has unusual dosing cycles. “Let’s say 50 mg of CBD does X. And then you may find that 150 mg doesn’t do X. But then maybe 300 mg does again. This is a gross exaggeration, but CBD dosage has some unusual properties. THC is the same.”

That’s why customizing it for your own body is important. As far as topical creams and ointments are concerned, they are very safe because there is very little systemic absorption, and the dose is less important.

But is it legal?
The US Food and Drug Administration (FDA) approved Epidiolex, a treatment for a rare form of pediatric epilepsy that contains CBD, and it is available nationwide. While individual states still have differing laws about medical marijuana and marijuana-derived CBD, hemp-derived CBD is legal on a federal level.

On December 20, 2018, the 2018 Farm Bill was signed into law, allowing broad hemp cultivation and the transfer of hemp-derived products across state lines for commercial and other purposes. It puts no restrictions on the sale, transport or possession of hemp-derived products as long as those items are produced in a manner consistent with the law, which states that hemp cannot contain more than 0.3 percent THC. Any cannabis plant that contains more than 0.3 percent THC would be considered non-hemp cannabis.

In the UK, hemp-based CBD with less than 0.2 percent THC is legal as a food supplement.

RESOURCES:
Dr Michael Lewis , MD, MPH, MBA: www.braincare.center
Constance Finley, Constance Therapeutics: www.constancetherapeutics.com
Professor Michael Barnes, MD: www.themedicalcannabisclinics.com
CBD Industry Association: www.cbdindustryassociation.org
Adam Abodeely, MD: www.reservemdhealth.com

References
1 Drugs, 2018; 78: 1791-804
2 J Psychopharmacol, 2011; 25: 121-30; Exp Clin Psychopharmacol, 2019; 27: 383-401
3 J Psychopharmacol, 2020; 34: 189-196
4 J Psychopharmacol, 2005; 19: 293-300
5 J Altern Complement Med, 2019; 25: 392-7
6 Anesth Analg, 2017; 125: 1638-52; Rheumatology (Oxford), 2006; 45: 50-2
7 Eur J Pain, 2016; 20: 936-48; Pain, 2017; 158: 2442-51
8 Bosn J Basic Med Sci, 2019; 19: 14-23
9 Front Pharmacol, 2017 ;8: 81
10 Phytother Res, 2013; 27: 633-6

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Article Topics: Cannabis
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