The Traditional Use of Cannabis Sativa in Medicine

For many centuries, Cannabis sativa has been employed in the treatment of a variety of diseases. In China, preparations from the flowers and resins of cannabis have been in use for about five thousand years, especially for the management of fever, malaria, constipation, absent-mindedness, menstrual disorders, gout, rheumatism, and pain.

 Cannabis has been used by Arabic cultures for similar medicinal purposes since medieval times. In the 1800s, western medicine utilized cannabis as a pain remedy, before aspirin was popularized. In the United States, cannabis was listed in the US Pharmacopeia from the 1850s up until 1942 and was prescribed for nausea and various pain conditions. In 1899, cannabis was listed in the first edition of Merck's Manual and recommended for the management of several conditions including epilepsy. Today, it is considered to be useful for glaucoma, nausea and vomiting, insomnia, anxiety, epilepsy, muscle spasms, pain, inflammation, and many more conditions.   

The Endocannabinoid System and Your Health

In the 1990s a fascinating discovery was made, the human body has an endocannabinoid system (ECS)—endo meaning internal. While many of us are aware of the fact that we have a respiratory system, a cardiovascular system, a neurological system, a digestive system, etc., most of us have probably never heard of the endocannabinoid system. Currently, we do not have a full and complete picture of what the ECS does, but we do know that the ECS helps fine-tune most of our vital physiological functions. It appears to function as the master regulator and promotes homeostasis affecting everything from sleep, appetite, pain, inflammation, memory, mood, and even reproduction. So, in basic terms, the ECS helps modulate the regulation of homeostasis across all major body systems ensuring that all systems work in concert with one another. Functionally, the ECS is able to regulate so many things, because there are ECS receptors found throughout the body—especially in our nervous, digestive and immune systems, and in most major organs. Our bodies naturally make cannabinoids, called endocannabinoids, which are messaging molecules that connect to the ECS receptors and regulate the system. Cannabinoids are also found in plants and these plant-based cannabinoids, called phytocannabinoids, also connect to ECS receptors and influence how the system functions. Hemp, or the cannabis plant, contains more cannabinoids than any other plant that we know of. While our body naturally makes its own cannabinoids, sometimes it may need a little boost. Cannabidiol (CBD) is a phytocannabinoid that we can supplement with that provides that little boost and helps our bodies naturally regulate the ECS, positively impacting the various functions that the ECS regulates. Additionally, CBD is non-psychoactive. It is very important to understand this point as many people are worried and scared of products that come from cannabis, assuming that all the cannabinoids that come from it are psychoactive or that any product made from it will be psychoactive. 

Phytonutrients in Cannabis

Cannabis contains more than 500 identified phytonutrients—plant-derived nutrients—of which, at least 104 are phytocannabinoids. The term phytocannabinoids is used to distinguish the naturally occurring plant-derived cannabinoids from the endocannabinoids, which, as discussed above, are the naturally occurring molecules made by the human body to regulate the ECS. 

Some of the major phytocannabinoids found in cannabis are cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), and the infamous tetrahydrocannabinol (THC). Although these compounds have similar chemical structures, they elicit very different pharmacological actions. THC is the major psychoactive component of cannabis whereas CBD is a major non-psychoactive constituent. CBD has been studied and found to provide a variety of health benefits—mostly stemming from how it impacts the ECS. 

What is CBD?

After being ignored for several decades, CBD is finally getting its place in the sun—for many years the focus has been on the cannabinoid THC because this is the compound that makes people feel “high.” However, the academic and consumer focus has shifted to understanding and utilizing other cannabinoids, namely CBD, for health promotion, as it is non-psychoactive. CBD has gained significant interest as a cannabinoid with numerous beneficial effects and studies indicate it positively impacts inflammation, neurodegenerative diseases, depression, schizophrenia, epilepsy and autoimmune disorders like multiple sclerosis, and arthritis.^{i ii}  Many CBD products found on the market today are manufactured from hemp and contain non-detectable to trace amounts (0.3% or less) of THC. Products that contain even trace amounts of THC do not contain enough THC to be psychoactive or make anyone feel “high.” 

How Does it Work?

Cannabinoids are a class of compounds that act as signaling molecules in the body, influencing the function of the ECS. The ECS is regulated by receptors that are found throughout the body and are especially concentrated in the central and peripheral nervous systems and the immune system. This unique system is composed of two main types of receptors, known as CB1 and CB2 receptors, and, similar to other physiological systems in the body, our cells naturally make compounds that bind to these receptors, providing an efficient cellular communication network. Studies show that signals sent through the ECS are critical to regulating a wide range of body processes, including appetite, pain, inflammation, digestion, immune health, and even mood.^{iii iv}

CBD does not activate the primary receptors of the endocannabinoid system in the same way that THC does—it is thought that this is what accounts for CBD’s lack of psychotropic activity. Instead, CBD exerts its pharmacologic effects through multiple mechanisms, including altering the way the body’s natural endocannabinoids interact with the CB1 and CB2 receptors. It should be noted that research suggests that CBD preparations work at different efficacies, and, on different mechanisms, based largely on the concentration of CBD in the body. Lower doses of CBD have been shown to have anti-inflammatory effects and may even modulate pain sensations throughout the body.^v Other studies have shown that at moderate doses, CBD alters neuroplasticity, stimulating beneficial changes in the brain in those with depression and anxiety, and may even improve sleep.vi At higher doses, CBD appears to exert unique effects on the neurological system and may be beneficial for people suffering from seizures and schizophrenia.^vii

CBD and Neurotransmitters

CBD produces many effects through multiple molecular pathways, one of them being its effect on neurotransmitter signaling. Other studies show that CBD has the ability to bind to dopamine receptors, likely contributing to its calming and anti-anxiety effects.^viii At higher concentrations, CBD directly activates the 5-HT (serotonin) receptor, boosting mood and potentially conferring an antidepressant-like effect. This receptor is implicated in a range of biological and neurological processes, including (but not limited to) anxiety, addiction, appetite, sleep, pain perception, nausea, and vomiting. Also, CBD has been shown to interact with the GABA receptors in a way that enhances its binding strength and can also increase the release of GABA from neurons.^ix GABA is the main inhibitory neurotransmitter—the sedating effects of Valium and other anti-anxiety drugs are mediated by GABA receptor transmission. CBD reduces anxiety by changing the shape of the GABA receptor in a way that amplifies the natural calming effect of GABA. Lastly, by affecting neurotransmitter homeostasis, CBD also appears to have positive effects on those with Parkinson’s disease.^x  

CBD and Pain

While not as well studied as the effects of CBD on neurotransmitters and brain function, CBD shows significant promise for helping reduce pain, especially neuropathic pain. Indeed, numerous animal studies have found that CBD supplements can reduce different types of neuropathic pain, such as those caused by pharmaceuticals and infections.^{xi xii} Significant data has suggested a role for cannabis extracts (that contain both THC and CBD—Natural Grocers only sells pure CBD supplements) for treating chronic pain, though it is not clear if the reduction in pain in these groups was related to THC or CBD.^xiii Other research suggests that CBD is a potent anti-inflammatory, which likely accounts for its ability to reduce pain in those with arthritis and other types of inflammatory disorders such as inflammatory bowel disease.^xiv

CBD and Inflammation and Autoimmunity

Not only does CBD show promise for reducing neuropathic and chronic pain, but research also suggests it has a mild anti-inflammatory effect.^xv The anti-inflammatory and immunomodulatory properties of CBD have also been shown to be active in the central nervous system. In an animal model of multiple sclerosis, CBD decreases the migration of white blood cells into the nervous system by decreasing the production of signaling molecules that cause cells to traffic to the nervous system and attenuates the activation of inflammatory cells.xvi A separate study demonstrated that CBD is also able to stimulate the production of anti-inflammatory regulatory T cells that directly inactivate autoimmune T cells.^xvii

CBD and Seizures

Currently, more than 20 different antiepileptic drugs exist for the treatment of epilepsy. However, 30% of patients with epilepsy continue to have seizures. Many new medications have been approved in the past two decades, but these have not reduced the proportion of patients with epilepsy that does not respond to medication. Recently, CBD has attracted attention as a potential treatment of epilepsy—specifically Lennox-Gastaut Syndrome and Dravet Syndrome.xviii Moreover, since 2013, the effects of CBD in the treatment of epilepsy have been studied at 10 major epilepsy centers worldwide.

In a placebo-controlled study, which included 15 patients suffering from “secondarily generalized epilepsy with temporal focus,” patients were randomly divided into a treatment group and a placebo group and given CBD 200300 mg/day or placebo.

CBD was tolerated in all patients, with no signs of toxicity. Of the eight in the treatment group, four were reported to be almost free of episodes of convulsion throughout the trial, whereas three others showed partial clinical improvement. CBD was ineffective in one patient.^xix In a more recent, larger study, researchers conducted a multicenter interventional trial aimed at establishing the safety, tolerability, and efficacy of CBD in patients with severe, intractable, childhood-onset, treatment-resistant epilepsy.

The authors recruited 214 patients. An approximate 37% median reduction in monthly motor seizures was reported and only 3% of patients in the safety assessment group discontinued treatment because of an adverse event. ^xx 

It should be noted that CBD administration may influence the pharmacokinetics of other drugs commonly used to control epilepsy. While research indicates these changes aren’t substantial, it is worth considering before trying CBD.^xxi

Topical CBD Products

CBD can be used in a variety of ways. Natural Grocers has chosen to carry both CBD for internal use that can be taken orally, and topical creams that contain CBD that can be applied to the skin. Research on topical creams is not quite as expansive as the research on oral CBD, however, there is still substantial evidence confirming its efficacy, and because the CBD is delivered through the skin, it may have improved bioavailability.xxii The best use of the CBD creams appears to be in conditions of inflammation and pain. For example, in one study on mice, topical CBD reduced inflammation and activation of immune cells that were contributing to experimental autoimmune encephalomyelitis, the mouse equivalent of multiple sclerosis.xxiii Other data indicate that topical CBD can be beneficial for arthritis, neuropathic pain, and colitis when applied to the skin.^{xxiv xxv xxvi}

Quality and Availability

In order to be legally sold by retailers, CBD must be purified from hemp, sometimes referred to as industrial hemp, and not the marijuana plant. This is because the hemp plant, in order to be classified as hemp, may only contain 0.3% THC or less, thus ensuring that the CBD products made from it are non-psychoactive. Hemp and marijuana are different varieties of Cannabis sativa. Since they are different varieties they have different properties and traits. The biggest difference between them is the amount of naturally occurring THC in the plant.  Hemp contains a very low amount of THC, 0.3% or less, whereas marijuana is abundant in THC and can contain anywhere from 15% to 40%. Additionally, marijuana has been selectively bred over the years into multiple varieties that contain various amounts of THC with a focus on increases its psychoactive properties. Hemp, on the other hand, contains an insignificant amount of THC but contains large amounts of CBD. Hemp has been bred to be used in foods (hemp seed oil, hemp seeds, and hemp protein), dietary supplements (CBD, hemp seed oil and hemp seed protein powders), skin products (hemp seed oil and CBD), clothing (hemp fiber) and paper (hemp fiber), thus, it has been bred to keep the THC content low (0.3% or less) and at a level that will not make anyone “high.”

CBD can be extracted from hemp using a variety of methods. Some of those methods involve using harsh chemicals, such as hexane. Unfortunately, when such chemicals are used, there is the potential for residues of them to remain in the CBD. However, there are better extraction methods that use non-toxic and more environmentally friendly processes, such as supercritical carbon dioxide—also known as CO2 extraction—and ethanol.   

Although the 2018 Farm Bill effectively legalized all products made from hemp, including CBD, by removing hemp from the Federal list of controlled substances this did not make CBD legal in all states. The bill allows states to pass their own legislation regarding the legality of CBD. Currently, only some states have established the sale of CBD products as legal. 

Conclusion

A long history of use, a good deal of experimental evidence, a large amount of positive anecdotal evidence, the fact that humans have an endocannabinoid system that regulates overall homeostasis, and a growing body of positive clinical studies, all point to the potential utility of CBD in the management of many different health conditions. The safety profile and usefulness of CBD has been exemplary thus far, and it represents a natural solution to many of the problems faced by Americans today.

References Available Upon Request