Down the Rabbit Hole with CBD

After all the media attention and marketing hype of the last few years, there’s still a lot to be cleared up about cannabidiol (CBD). So…have a seat and get comfortable with a cup of tea or glass of wine.  🙂

For two years I’ve been researching cannabidiol, commonly known as CBD and a member of the family of cannabinoids.

Hemp is a variety of the Cannabis sativa plant, grown specifically for industrial uses. Hemp has very low concentrations of THC and higher concentrations of cannabidiol (CBD). The cannabis plant that many know as marijuana is a separate plant, and has high concentrations of THC, and very low CBD.

Hemp and marijuana both contain cannabinoids, as well as 400 other compounds.  One of the most famous cannabinoids is THC — the one that’s psychotropic and provides that “stoned” feeling. Hemp, however, is not a source of THC.  Both hemp and marijuana contain the non-psychotropic cannabidiol CBD, which is revealing itself to be quite a fascinating and important substance.

By the way, cannabinoids are not totally unique to hemp and cannabis; they’re found in other plants as well, such as kale and broccoli.

Hemp seed oil versus hemp oil
Hemp seed oil is made from extracting the oil from hemp seeds.  There is little to no CBD in hemp seeds, and therefore none in hemp seed oil.  But when the hemp stalks, flowers, and leaves are pressed for oil — hemp oil — the CBD percentage is quite substantial.

CBD from hemp is legal in all 50 states and the EU. Note that CBD from marijuana (Cannabis oil) is only legal in states that have approved medical marijuana.

What’s the big deal about CBD?
Research has shown that cannabinoid receptors are located throughout the body in mammals, birds, reptiles, fish, sea urchins, leeches, mussels, and humans.  Cannabinoid receptors are not found in insects.  These receptors are part of the biological endocannabinoid system found throughout the body: in the brain, organs, connective tissues, glands, GI tract, and immune cells.  While the cannabinoid system performs different tasks, the goal is the same: maintenance of a stable internal environment despite fluctuations in the external environment. This is known as homeostasis.

Scientists estimate that the endocannabinoid system evolved in primitive animals over 600 million years ago. Some researchers think that cannabinoid receptors may be more numerous than those of any other receptor system.  At present, two cannabinoid receptors have been identified: CB1 and CB2.   Many tissues can contain both CB1 and CB2 receptors, and there is speculation among scientists that there are more cannabinoids waiting to be discovered.

Humans and animals produce endocannabinoids (“endo” means “within”) in our bodies to stimulate the cannabinoid receptors.  These molecules are long-chain polyunsaturated fatty acids derived from membrane phospholipids and arachidonic acid, one of the most abundant fatty acids in the brain.  The body metabolizes omega-6 (linoleic acid) to produce arachadonic acid. The endocannabinoids have a short life before being degraded by intracellular enzymes. The body does not store endocannabinoid molecules; they are produced on demand.

Phytocannabinoids are molecules synthesized by plants, and stimulate cannabinoid receptors in the body.  CBD is a phytocannabinoid.

Now, here’s the miracle of CBD: not only does it fit into the cannabinoid receptors and stimulate them itself, but it also increases the availability of endocannabinoids by stopping a specific enzyme (FAAH) from degrading them, providing a greater supply of cannabinoids for the body.

Basic functions of the endocannabinoid system
The regulation of homeostasis by the cannabinoids can affect:

• Metabolism
• Pain
• Mood
• Movement
• Memory and learning
• Immune Function
• Inflammation
• Digestion

 Cannabinoid receptors in the body

• CB1 receptors are expressed in the brain, liver, lungs, smooth muscle, gastrointestinal tract, vascular endothelium, reproductive organs, immune system, sensorial peripheral nerves and sympathetic nerves.
• CB2 receptors are expressed in immune system cells such as macrophages, neutrophils, monocytes, B-lymphocytes, and T-lymphocytes.  CB2 receptor expression also includes skin nerve fibers and bone cells such as osteoblasts, osteocytes, and osteoclasts.

U.S. government patent
In April, 1999, the federal government patented cannabinoids as antioxidants and neuroprotectants.  US Patent 6630507 states that cannabinoids are “useful in the treatment and prophylaxis of a wide variety of oxidation associated with diseases like ischemic, age-related, inflammatory, and autoimmune diseases.”

This is important because the root of many diseases and imbalances in the body is oxidative stress.  The body produces its own antioxidants such as glutathione, alpha-lipoic acid (ALA) and CoQ10 but chronic stress, pollution, and environmental and food stressors can result in the body not having enough antioxidants to fight the cascade of free radicals.

The hemp plant: More than just CBD
As exciting as CBD is for health and for healing, there are other components of the hemp plant that are important to the body system.  These include terpenes and bioflavonoids.

Terpenes are organic compounds found in many plants.  Some of the more aromatic plants with terpenes include rosemary, oregano, mint, and basil. Hemp contains over 200 terpenes, synergistically interacting with cannabinoids in the plant.  Among the noted terpenes in hemp are myrcene and beta-caryophyllene (BCP). Myrcene is found in lemon grass and many strains of marijuana.  It is known for its antimicrobial and antiseptic properties. Beta-caryophyllene is found in cloves, rosemary, and hops.  It binds to the CB2 receptor and is considered a functional CB2 agonist.  This is a unique terpene because it works directly with the endocannabinoid system.  It can target CB2 receptors to reduce inflammation and pain.

Bioflavonoids are a large class of organic plant compounds found in, among other sources, citrus fruits, legumes, beetroot, pepper, and onions.  Hemp provides the bioflavonoids beta-sitosterol, apigenin, and quercitin.  It also has a unique sub-class of flavonoids called cannaflavines.  These flavonoids are being studied by researchers, but already we know that cannaflavin-A is an inhibitor of the pro-inflammatory prostaglandin PGE-2.   The drug misoprostol, commonly used for hindgut ulcer horses, is a synthetic PGE-1 prostaglandin which helps regulate the pro-inflammatory PGE-2.  Cannaflavin-A, by inhibiting PGE-2, could be beneficial in supporting prostaglandin regulation for hindgut ulcer horses.

Other nutritional components
Besides cannabinoids, terpenes, and bioflavonoids, hemp plants also contain fiber, protein, fat, and carbohydrates, plus vitamin E in the form of alpha tocopherol and gamma tocopherol.  Hemp also provides calcium, magnesium, phosphorus, copper, zinc, and manganese.

The protein in hemp is composed of two types: edestin and albumin.  Proteins are classified as structural (fibrous) or biologically active (globular).  Structural proteins include collagen and keratin, which are the main constituents of bones, skin, hair, ligaments and hooves.  Biologically active proteins are mainly globulins and include hormones, hemoglobin, and immunoglobulins.  Edestin and albumin are globular proteins, which some consider to be the backbone of cellular DNA.

The fact that CBD is found with terpenes, bioflavonoids, and other cannabinoids is known as the “entourage effect” —  compounds that synergistically interact to magnify the therapeutic benefits of the plant’s individual components.

Eighteen years with hemp
I am by no means a hemp expert.  I was introduced to hemp seeds and hemp oil in 2000 by a small family-owned Canadian company, and quite honestly I fell in love with hemp — for its nutritional benefits and its ecological ones.  Ten years ago, BioStar was the first equine supplement company to bring hemp seed oil to the market for horses, quickly followed by hemp protein and hemp fines, which we use in Optimum EQ.  We still purchase from the same Canadian company I was introduced to in 2000.

The current craze for CBD
If you’re wondering why it has taken me two years to study CBD, it’s because CBD has become a marketing phenomenon and nightmare rolled into one: so many health claims, so many different forms of CBD oil, so many different processes for extracting it.  I can’t tell you the number of CBD oils I have purchased and been severely disappointed.

Searching for the right hemp
My disappointment with the various CBD oils led me to the conclusion that I wanted a whole-food CBD formula that provided the matrix of nutritional factors, and not simply the isolated CBD.

In my research I learned that some strains of hemp have higher CBD content than other strains, but that there’s no way to determine this by just reading a label.  CBD has exploded in the market, the price for bulk CO2-extracted CBD oil (considered the best manner of oil extraction) is shockingly expensive, ranging from $4200 to $5800 a kilogram (2.2 lbs.) of oil.  Because of the expense, companies will sometimes cut the oil with other oils like coconut to reduce their cost, but that also reduces the percentage of CBD.  It has become clear to me that, in the CBD oil world, you really do get what you pay for.

Other factors to consider
Another factor to consider with CBD is from which part of the plant it is extracted.  Some hemp processors only process the oil from seeds (which have negligible CBD amounts), plus the stalks.  In contrast, premier CBD oil is processed from the whole plant: flowers, leaves, seeds and stalks.

Complicating things further, there’s an ongoing debate about the quality of hemp from the US versus hemp from the EU.  I wanted hemp from the US, but it had to be organic, and that’s hard to find.  The hemp plant has absorbing qualities that can draw up contaminants from the soil.  Hemp grown in poor soil may have high levels of lead and other heavy metals.  The EU uses far less herbicides and pesticides than we do, but I wanted to support American farmers.

I found a couple of US and EU sources of hemp meal, which is what is left over from the oil extraction, but the percentage of CBD was so low that I decided to set CBD aside for inclusion in a formula and wait until I could find what I was looking for.

Misleading customers with labeling
One of the challenges I found in studying hemp CBD products is that some companies mislead consumers with the way they label CBD dosage; they will often provide the weight amount in milligrams of total hemp oil, rather than the amount of active CBD per serving.

Miracle from Oregon
Oregon happens to be the state where we found our organic pumpkin seed meal, which is a rare find today, as most organic pumpkin seeds and meal comes out of China.  So I suppose it shouldn’t have surprised me too much that a hemp farmer in Oregon, growing organic, high-CBD hemp, who extracts the oil from the whole plant using supercritical CO2 extraction, would have hemp meal (pressed flowers, leaves, seeds, stems) with almost double the amount of CBD found in other hemp meal material.

For me it was the eureka moment: here was the hemp meal I was waiting for!

Benefits of CBD for horses and dogs
A simple search on Science Direct for studies and research on CBD gives 2,572 results.  In the Gastrointestinal Endoscopy category alone there are 25 published articles, and in Gastroenterology there are 53.  In 2017 there were 248 research articles published on CBD.  So far in 2018, there have been 260.  A search for “cannabinoids” in PubMed for the years 2010–2015 results in 1827 publications.

Based on the science, the CBD health benefits for horses and dogs are numerous:

• Anti-inflammatory action to help reduce chronic and systemic inflammation, including in the GI tract
• Helps protect the gastric mucosa against lesions, erosions, and inflammation
• Reduces oxidative stress linked with chronic disease
• Provides neuroprotective agents
• Can reduce chronic pain
• Can play a positive role in metabolism by stimulating genes and proteins to enhance the breakdown of fat
• Increases the number and activity of mitochondria for cellular energy
• Can reduce anxiety
• Provides immune system modulation
• Can help the body system attain wellbeing through the regulation of homeostasis by the body’s cannabinoid system.

Encouraging new research
Scientists in Israel have found that CBD enhanced fracture healing in part by stimulating lysyl hydroxylase, an important enzyme involved in bone healing, by acting on bone-building cells called osteoblasts.

A study published in Brain Research Bulletin (2018) and a study by researchers from the Pontifical Catholic University of Brazil (2014) examined the link between excessive levels of iron (associated with impaired mitochondrial function) and degradation of the brain.  These particular studies point out how CBD helped prevent the harmful effects of iron on mitochondrial DNA.

In June, 2018, the FDA approved Epidiolex, an epilepsy drug derived from cannabis.  This is the first cannabis-based treatment for seizures.

Single-molecule CBD versus whole-plant CBD
The health benefits of CBD have not been lost on the pharmaceutical industry, and the industry as a whole has long benefitted from providing medication in a single-molecule form, trashing the concept of herbal medicines.  A lot of research has been done on single-molecule CBD including demonstrating that it is a biphasic medication — one that works well up until a certain dose, but above that loses its therapeutic benefits drastically, along a bell curve.

While single-molecule CBD has been shown to have significant limitations, data published in Pharmacology & Pharmacy (2015) showed that whole-plant CBD showed itself to be more medicinally powerful.  Researchers found the full-plant CBD to be a more versatile medication because of the presence of other cannabinoids, terpenes, and bioflavonoids that all help to deliver results that single-molecule CBD can’t.

The synergy of the whole
Like everything Nature does, there is interconnectedness.  We know with pharmaceuticals — many of which began with the isolation from a plant source and were then recreated in a laboratory — that there are side effects and warnings to consider.  Nature didn’t intend on humans and animals eating isolated nutritional factors or medicinal components.  The ancient healers like the Chinese and the Hindus recognized the significance and energy of plants and foods, the life force if you will, of the whole.

The whole plant is greater than the sum of its parts.

Coming soon
BioStar has now augmented our own whole-food hemp CBD with other anti-inflammatory and super antioxidant foods to provide a multi-faceted formula for wellness.

We will be offering our new whole-food CBD formula for dogs in September, 2018, and our new whole-food CBD formula for horses in October 2018.

Stay tuned!

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075023/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685274/

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wmts.83

https://www.sciencedirect.com/science/article/pii/S0924977X13003027

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2982.2011.01689.x

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333598/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748879/

https://www.biotrack.com/cbd-and-bone-fracture-healing-the-best-data-published-for-medical-marijuana-in-fifty-years/

https://www.ncbi.nlm.nih.gov/pubmed/21238581

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/