The Science Behind CBD

Inside all mammals is an intricate network of receptors that play important roles in health, healing, and homeostasis. The endocannabinoid system (ECS) was discovered in the early 1990s, but evolutionary evidence indicates that some version of an ECS has been preserved in all vertebrates (as well as sea squirts and nematodes) for at least 600 million years, suggesting that these receptors and the substances that bind to them play a crucial role in the functioning of life.  There are three main receptors associated with the ECS: CB1, CB2, and TRPV1. According to Raphael Mechoulam, the chemist who first isolated THC in the 1960s, these receptors are most abundant in the brain and they are not found everywhere – they persist in specific areas that are involved in important bodily processes like coordination & movement, emotions, memory, reduction of pain, and reproduction.  CB1 was discovered in 1990 and is cited as one of the most common receptors found in the brain, again a testament to this system’s key role in neurological processes. CB2 was the second receptor to be discovered. It is largely found in immune cells, although it can be found in other parts of the body including the digestive system and peripheral nervous system. TRPV1 is involved in pain response, inflammation, and regulation of body temperature. It is known as the attachment site for capsaicin – the compound responsible for the burning sensation we associate with chili peppers.

The receptors mentioned above are nothing without the substances that attach to and activate them – the endogenous cannabinoids that our bodies produce. The most studied of these endocannabinoids are AEA (nicknamed anandamide after the Sanskrit word for “bliss”) and 2-AG. Both can attach to CB1 and CB2, although AEA prefers CB1 and 2-AG prefers CB2. Dustin Sulak, an Osteopath who uses cannabis in his practice, describes these endocannabinoids as keys that open the same locks (receptors). Depending on which keys are used, the locks will open to different doors. This system, which is responsible for maintaining various bodily processes, can become imbalanced in various ways: receptors can be over or under active and endocannabinoid levels can be too low or too high. It’s interesting to note that in individuals with some cancers like breast, gliomas, and lymphomas, cells tend to have more CB1 and CB2 receptors. Some researchers think that this phenomenon is part of the body’s effort to fix the disorder.  As research into this system continues, scientists are looking into the relationship between the ECS and certain diseases. The following table taken from a review article about the ECS lists various conditions in humans and their associated effects on the ECS:

If the ECS is imbalanced, what can be done to bring it back to normal? Medications, alternative therapies, supplements, and life-style choices can all influence an individual’s ECS. In animal studies, certain opiates and steroids enhanced endocannabinoid activity. In mice & rats, supplements and alternative therapies have been shown to influence the ECS: probiotics modulated CB1 activity and acupuncture increased CB2 activity in skin tissues. Intense exercise has been found to increase AEA levels in both dogs and humans – scientists think that this may account for the “runner’s high” that is apparent after heavy exercise.  This idea of supplementing a troubled ECS brings us to the elephant in the room: cannabis and the phytocannabinoids that are found so abundantly in this plant.

Phytocannabinoids are substances found in plants (most notably in Cannabis sativa) that are able to stimulate the same ECS receptors mentioned previously. There are at least 113 known phytocannabinoids in the cannabis plant; the most well-known and studied of these phytocannabinoids is THC but in recent years, this molecule’s non-psychoactive counterpart, CBD, has received much media attention.  CBD or cannabidiol was first isolated in 1963 by Raphael Mechoulam – one year before the chemist elucidated the structure of THC.  Both substances can modulate the ECS, but CBD does not alter the mind or behavior in the same way THC does. THC attaches directly to CB1 and CB2, much like the endocannabinoids AEA and 2-AG. CBD’s effects are achieved in a different manner: the molecule affects these receptors, but not by directly attaching to them in the same way as THC and AEA.

Newer research indicates that CBD does attach to CB1—just not at the same receptor site as THC or AEA. By attaching to a different area, it is thought that CBD can change the shape of the receptor and thus influence how this receptor will interact with the other substances that bind to it.  CBD can also influence the ECS in other ways: it can suppress the enzyme that breaks down AEA, thereby prolonging the endocannabinoid’s effects. It can also directly attach to TRPV1 and other receptors that play roles in the cardiovascular and neurological systems.

CBD’s ability to influence the ECS may account for the historical and anecdotal evidence that suggests its positive role in a number of conditions including: Dravet’s syndrome, some cancers, and various types of pain.  In pre-clinical studies involving animal models, CBD has been shown to have the following properties: anti-inflammatory, antioxidant, anti-nausea, anticonvulsant, anti-anxiety and neuroprotective. CBD is also anti-proliferative in regards to certain cancer cells.

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In 1991, Harvey et al. compared the metabolism of CBD in rats, dogs, and humans (1). While they did find that CBD is metabolized differently among these animals, they concluded that overall, the way these animals metabolized the CBD showed the same trends.  The human and canine CBD metabolic process may vary, but this has not stopped pet owners from using hemp products in an attempt to combat the symptoms and diseases that both species seem to share.
In the spring of 2016, the American Veterinary Medical Association (AVMA) published a study that investigated the growing trend of pet owners who use hemp products on their pets. What they found suggests that some pet owners believe that hemp products help alleviate numerous conditions with minimal side effects.

The authors of this study conducted a survey of visitors to one hemp product company website for one month in 2015.  Of the 631 respondents who said they use hemp products on their dogs, the majority indicated that they use them for conditions diagnosed by their veterinarian, with the most common being cancer, seizures, anxiety, and arthritis. They also reported that these products were moderate to very helpful in improving their pet’s well-being and that they had a positive impact in relieving pain and anxiety, as well as helping with sleep. Side effects reported were minimal: sedation and over-active appetite.

Overall, owners seem to be using hemp because they either prefer “natural products” and want to supplement conventional therapies.  While this study group was limited and subject to the biases of each individual pet owner, the findings bring to light some interesting trends and reinforce much of the anecdotal evidence reported by media outlets of cannabis’ ability to mitigate certain disorders.

See “Resources & Links” tab for links to great information on using cannabis for dogs and cats

  • References

[1] Harvey, D. J., Samara, E., & Mechoulam, R. (1991). Comparative metabolism of cannabidiol in dog, rat and man. Pharmacology Biochemistry and Behavior, 40(3), 523-532.

Mushrooms have been used in Eastern medicine for centuries for a variety of ailments.  Recent studies (as early as the 1960s) involving cell cultures, animal models and even clinical trials are starting to show the health benefits of these fungi. The primary beneficial component of medicinal mushrooms are polysaccharides called beta-glucans. These beta-glucans are able to modulate the immune system and help the body appropriately respond to various stressors. Because these beta-glucans either magnify or reduce the body’s natural responses, they tend to have little side-effects and can support many major bodily systems.

While mushrooms likely have numerous health benefits, most studies involving medicinal mushrooms focus on their anti-cancer properties. Beta-glucans are able to stimulate the body’s white blood cells to elicit anti-tumor responses. Studies have found that these compounds are useful in the prevention of cancer as well as supporting the immune system while the body is undergoing conventional cancer treatments like chemotherapy.  Listed below are five well-studied medicinal mushrooms and some of their purported health benefits, according to recent studies.

Shiitake (Letinula edodes)

Shiitake mushrooms are the source of two extensively studied medicines: LEM, a polysaccharide that is derived from the mushroom’s mycelium and lentinan, a beta-glucan. Both of these compounds enhance the immune system and have shown anti-cancer properties. Additionally, various compounds found in this mushroom have shown antimicrobial, antiviral, antibacterial, antifungal, and antioxidant properties as well as cardiovascular & hepatic benefits in animal studies.

Reishi (Ganoderma lucidum)

Studies on Reishi attribute its anti-tumor properties to at least three different polysaccharides as well as triterpenoids (bitter tasting compounds). These polysaccharides activate cells in the immune system to produce substances that in turn stop blood flow to tumors. They are also thought to interfere in the process by which a normal cell becomes cancerous. Reishi mushrooms have also shown similar health benefits to shiitake mushrooms in animal models.

Phellinus (Phellinus linteus)

Like the other medicinal mushrooms listed above, Phellinus mushrooms can enhance immune function and aid in anti-cancer activities. When administered orally in mice, Phellinus extract significantly inhibited the growth of colon cancer.  Additionally, the application of Phellinus extracts to stomach and cancer cells showed anti-cancer activity without harming normal cells.

Poria (Poria cocos)

Like many medicinal mushrooms, Poria can enhance immune function and may be beneficial as an adjunctive or alternative option to certain cancer therapies.
Poria’s triterpenes are also thought to have anti-carcinogenic effects: in one study involving human pancreatic cancer cells, these compounds arrested the cell replication cycle, thereby preventing them from proliferating.

Turkey tail (Coriolus versicolor)

Turkey tail are of particular interest to scientists involved in cancer and immunotherapy. Two polysaccharides derived from turkey tail mushrooms have showed much promise in clinical trials involving various cancers: PSK & PSP. Japanese scientists have been conducting clinical trials of PSK since the 1970s. They have found that PSK significantly extended the five-year survival rate in patients with stomach, colon-rectum, esophageal and nasopharynx cancers as well as certain breast and lung cancers. PSP has reached Phase III clinical trials in China. In a double blind study, it extended the five-year survival rate in esophageal cancer patients. Moreover, it significantly improved the quality of life, provided pain relief, and boosted the immunity of the majority of stomach, esophageal, lung, and ovarian cancer patients to which it was administered to. Because of both PSK & PSP’s ability to boost the immune system and mitigate side-effects of chemotherapy, some scientists see them as good adjunctive options to traditional cancer therapy regimens.

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Each batch of our treats and oil are third party tested for potency, microbial content, and pesticide and solvent residue by Steep Hill Labs in Berkeley, CA.

Lab Results

Hemp and marijuana are both derived from the same plant species:  Cannabis sativa.  Within C. sativa are many plant varieties that are bred for various purposes.  Plants grown to produce fiber and seed products are called “hemp” and plants grown for medicinal or recreational purposes (traditionally, a high THC content) are referred to as “marijuana.”  These definitions have let to the conventional notion that marijuana products are high in THC while hemp products contain little or no THC and are high in CBD.  As the cannabis industry continues to grow and research attempts to further elucidate genetic differences between cannabis and hemp, this terminology and how we classify cannabis plants could (and should) change.

For policymakers, a limited and often misinformed knowledge in cannabis genetics makes differentiating hemp and marijuana a difficult and superficial task.  In the 1970’s Canadian scientist Ernest Small published a taxonomic report in which he drew an arbitrary line: he decided that 0.3% THC in a sifted batch of cannabis flowers was what determined the difference between hemp and marijuana.  This decision, written 30 years ago in obscurity has had far reaching ramifications for how countries all over the world regulate cannabis.  In the US, any cannabis plant with a THC content higher than 0.3% is deemed marijuana and therefore federally illegal.

What makes our CBD products different?

  • Our oil is sourced from a Colorado based company that utilizes organic, locally grown hemp as the raw material for their CBD rich oils.  We believe our oil is superior to the majority of CBD oil that is sourced from China or Europe.
  • To further guarantee a quality product, our treats and oils have been third party tested to ensure that they are free of pesticides, heavy metals, residual solvents and other toxins.  Our products are also tested for consistency and potency so you can be sure you are giving your pets the same treat or tincture each time.
  • We’ve also added a certified organic blend of five medicinal mushrooms for additional healthy support.
  • Most of our ingredients are organic and our chickens are pasture raised and organically fed
  • Folium’s CBD oil is derived exclusively from hemp.
  • On February 7, 2014, the US Congress signed the Farm Bill of 2013 into law, a section of which was entitled “Legitimacy of Industrial Hemp Research” defining industrial hemp as distinguished from marijuana as having <.3% THC. The Bill authorized State departments of agriculture to have oversight of hemp in states where hemp is legalized to be grown for research or agricultural pilot programs which “study the growth, cultivation or marketing of industrial hemp”.
  • Colorado passed Amendment 64 on December 10, 2012 which now qualifies as a “pilot program” under federal law
  • The Amendment also exempts Industrial Hemp (derived from cannabis but with <.03% THC) from the legal definition of “marijuana”.
  • All of Folium’s plants have passed inspection by the Colorado Department of Agriculture as part of the pilot program.
  • Companies that are producing CBD in Colorado are selling their products nationally under the definition of a pilot program (as are sellers in other states with authorized hemp pilot programs).
  • Folium’s CBD oil is not only <.3% THC, but in fact contains 0% THC (see test results on our website). Their products (and as a result, Holistic Hound’s CBD products), are tested and proven to have 0% THC.
  • To our knowledge, CBD dog treats have been shipping freely across 50 states for the last 18+ months with no interference by the state or federal governments
  • The only issue we are aware of are FDA crackdowns on several companies earlier this year (e.g., Canna-Pet) because of supposed health claims made by those companies.  Those companies are still selling and shipping their products but had to make changes to their website, FB, etc.
  • To our knowledge, no retailer of CBD dog treats in any state has been challenged by either state or federal governments despite explosive growth in sales over the last 18+ months