As hemp extracted compounds* medicinal qualities continue to make waves across the country, more states are starting to look into limited medical  legalization laws so their residents can get access to Hemp extracted compounds* to treat their debilitating medical conditions.

If a patient is unlucky enough to live in a state with no laws in place or no legal access to hemp extracted compound* products, he or she may feel as if there’s no viable alternative that can provide the same relief.

Here’s where hemp extract products* come in. There’s been much debate suggesting that extract* derived from industrial hemp has the same properties as cannabis-derived extract*, making it a potential alternative for patients who can’t legally access medical cannabis but can legally acquire hemp-derived extract* products. A lot of people aren’t entirely familiar with hemp extract compounds*, however. What exactly is there to know?
Here are a few facts about extract* derived from industrial hemp:

  • Agricultural hemp and medical marijuana both come from the Cannabis Sativa L. plant.
  • Agricultural hemp, which is often referred to as “hemp stalk,” grows differently than THC-containing cannabis, and looks similar to bamboo.
  • THC-producing marijuana plants are grown to an average of five feet in height, spaced six to eight feet apart. Agricultural hemp is grown to a height of 10 to 15 feet or more before harvest, placed three to six inches apart.
  • Hemp has little potential to produce high-content THC when pollinated.
  • As long as agricultural hemp plants are pollinated by members of their own crop, the genetics will remain similar with low levels of THC.
  • There is a strong legal argument that production and distribution of CBD oils/products derived from imported raw material industrial hemp is not a violation of the Controlled Substances Act (CSA); in fact, one Colorado law firm has published a written opinion making the case.


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Cannabidiol 101: A Peek Into Cannabinoid Chemistry

The endocannabinoid system (ECS) is a complex signaling network within the human body that uses specialized compounds known as cannabinoids to control various bodily processes by interacting with different receptors and regulatory enzymes.

Cannabidiol (CBD) is often referred to as a “phytocannabinoid.” Phytocannabinoids are plant derivatives that contain a number of diverse chemical compounds that can affect appetite, metabolism, pain sensation, inflammation, thermoregulation, vision, mood, and memory. It’s important to note that phytocannabinoids are any plant-derived product capable of either:

  1. Directly interacting with cannabinoid receptors;
  2. Sharing chemical similarities with cannabinoids that allow them to interact with other components of the ECS; or both

 CBD is the second most prominent compound found in the Cannabis sativa l. plant, while THC is the first. Proponents claim that, unlike THC, CBD can be legally purchased and used throughout the United States when derived from agricultural hemp. It is non-psychoactive and is thought by some to have a much broader range of medical applications, including beneficial effects on neurodegeneration, autoimmune disorders, heart, and liver health.

Cannabinoids and the Immune System: Immuno-Cannabinoid Effects

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As discussed in previous articles such as Cannabidiol 101: A Peek into Cannabinoid Chemistry and What Makes Cannabis Medicine?, the endocannabinoid system, or ECS, is a remarkably complex signaling network that has widespread effects within the body. In fact, many studies have been published examining the effects of various components of the ECS on appetite, metabolic health, blood sugar regulation, obesity, pain sensation, oxidative stress, thermoregulation, eye health, mood, memory, and much more.

However, one particularly interesting therapeutic application of the ECS is its effect on the immune system, or what some scientists refer to as “immuno-cannabinoid” modulation. Simply stated, the ECS can help regulate or vary the properties, tone, and overall function of the immune system.

Although the immunomodulatory effects of the ECS have not been fully elucidated, here’s what we do know. First, at optimal concentrations, certain cannabinoids can reduce inflammatory responses in patients with autoimmune diseases (e.g., multiple sclerosis, arthritis, lupus, encephalomyelitis, Parkinson’s). Cannabidiol is particularly potent in this regard.

Second, cannabinoids have been shown to play a role in modulating neurogenesis and neurodegeneration. For example, evidence from numerous studies demonstrates beneficial effects of cannabinoids on animal models of stroke, head injury, cerebral ischemia, as well as beta-amyloid induced tau protein phosphorylation (tauopathy). It has been established that the immune system plays a critical role in many of these neurodegenerative and neuroinflammatory conditions.
It is important to recognize that these immunomodulatory effects are the result of a coordinated cascade of responses from the so-called “innate immune system” as well as the “adaptive immune system.” The immune system is a huge network of various immune cell types that express many different receptors (think of them as locks), and release and respond to many cytokines/hormones (think of these as keys that help open those locks).

Cell-mediated immunity is one of the key components of the adaptive immune system that responds by utilizing specialized T-cells and natural killer (NK) cells to seek out and neutralize pathogens, viral infected cells, and tumor cells that are recognized as foreign. Humoral immunity complements the cell-mediated system by using B-cells and developing antibodies to neutralize antigens or pathogens that are recognized as foreign.

If there is an imbalance between cell mediated and humoral immunity, it results in disease and dysfunction. For example, multiple sclerosis is an example of an autoimmune disease, in which the cell-mediated immune system is hyper-activated against the individual’s own brain and nervous system—as if it were foreign. Interestingly, the ECS and cannabinoids have been shown to play a key role in “balancing” the various arms and components of the immune system.

Few would argue that heavy, chronic use of unregulated marijuana can have deleterious effects on several aspects of health. However, scientists studying the effects of the ECS on the immune system, neuroinflammation, inflammatory arthritis joint health, and even systemic inflammation have uncovered remarkable benefits from naturally occurring and endogenously produced cannabinoids.

Various phytocannabinoids from cannabis, even within agricultural hemp, are showing enormous potential for optimizing and restoring balance to the immune system. Ultimately, understanding the intricate plasticity of cannabinoid compounds, cannabinoid receptors, and the enzymes that synthesize, hydrolyze, and metabolize them, and the complex cross-talk that exists with other organ systems in the body, will undoubtedly rewrite medical textbooks worldwide.

References:

Fernandez-Ruiz J, et al. (2013). Cannabidiol for neurodegenerative disorders: Important new clinical applications for this phytocannabinoid? Br J Clin Pharmacol. 75(2): 323-333.

Tanasescu R and CS Constantinescu. (2010). Cannabinoids and the immune system: An overview. Immunobiology. 215: 588-597.

Klein TW, et al. (2003). The cannabinoid system and immune modulation. 74: 486-496.

Downer EJ. (2011). Cannabinoids and innate immunity: Taking a toll on neuroinflammation. The Scientific World Journal. 11: 855-865.

Croxford JL, Yamamura T. (2005). Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J Neuroimmunol. Sep;166(1-2):3-18.

Massi P, Vaccani A, Parolaro D. (2006). Cannabinoids, immune system and cytokine network. Curr Pharm Des. 12(24):3135-46.

Cannabinoid Physiology: Influence on Metabolism and Body Fat Regulation

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There is accumulating scientific evidence that the endocannabinoid system plays an important role in how the body regulates energy (calorie) balance, as well as carbohydrate and fat metabolism. As such, the endocannabinoid system (ECS) is an oft-overlooked key in the regulation of body weight and body composition (note: “body composition” here refers to the relative amounts of lean mass and body fat).

Scientists have uncovered that endo/phytocannabinoids act via central (brain) and peripheral (gut, liver, muscle and fat) mechanisms. Central control of appetite, satiety, cravings, and food-seeking behavior involves a complex interplay between various centers of the brain. Different areas of the brain receive information in the form of nutrients, hormones, and signaling molecules from body fat tissue, the gut, blood, and peripheral sensory receptors.

It is accepted that endocannabinoids and certain naturally occurring phytocannabinoids in cannabis activate cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors), in addition to various other G-protein coupled receptor families (e.g., TRPV1, GPR55 and others). The CB1 receptor is believed to be responsible for most of the central effects of cannabinoids on hunger/satiety centers of the brain that affects appetite and energy intake.

Moreover, CB1 receptors have also been discovered to exist in the peripheral tissues outside of the brain, including key organs such as adipose (fat), liver, gut, pancreas, and skeletal muscle. The interplay of these central and peripheral mechanisms and their effects on body weight and body composition is currently under intense scrutiny.

Interestingly, over-activation of the endocannabinoid system, primarily via CB1 activation, has been suggested to contribute to increased abdominal obesity, glucose uptake into adipocytes (fat cells), and insulin resistance in muscle. This “metabolic dysfunction” sets up a vicious cycle whereby further insulin resistance in muscle and liver increases abdominal obesity and further CB1 over-activation, resulting in greater food-seeking behavior and increased appetite.
Animal studies have supported this hypothesis by showing that stimulation of CB1 receptor with anandamide induces both increased food intake and body weight gain. Proof-of-concept of the potential effectiveness of CB1 receptor blockade in humans has been established with preclinical and clinical studies of rimonabant, the CB1 receptor reverse agonist (i.e., it induces an opposite response vs. CB1 activators).

These studies have uncovered not only a reduction in food intake, but also improvements in body composition (e.g., preferential losses of body fat while retaining lean mass). In addition, treatment with rimonabant was accompanied by improvements in cardiometabolic risk factors beyond what would have been expected with weight loss alone.

Another study published in 2012 by Farrimond et al. examining the effects of different phytocannabinoids, such as cannabinol and cannabidiol, on feeding patterns in rats supports the theory that different cannabinoids modulate CB-1 receptors and hence appetite and metabolism with opposing effects. This study demonstrated that cannabinol increased food intake and body weight gain, while cannabidiol decreased food consumption and weight gain. Cannabigerol had a neutral effect on chow consumption and feeding behavior in this particular rat study.

Collectively, these studies have clearly demonstrated that dysregulation of cannabinoid physiology can have detrimental effects on whole body energy (calorie) homeostasis, glucose and lipid metabolism, and body composition. Conversely, optimizing ECS tone appears to have beneficial effects on metabolism and body composition regulation.

References:

Geurts L, Everard A, Van Hul M, Essaghir A, Duparc T, Matamoros S, Plovier H, Castel J, Denis RG, Bergiers M, Druart C, Alhouayek M, Delzenne NM, Muccioli GG, Demoulin JB, Luquet S, Cani PD. Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota. Nat Commun. 2015. Mar 11;6:6495.

Di Marzo V. The endocannabinoid system in obesity and type 2 diabetes. Diabetologia. 2008 Aug;51(8):1356-67.

Romero-Zerbo SY, Bermúdez-Silva FJ. Cannabinoids, eating behaviour, and energy homeostasis. Drug Test Anal. 2014 Jan-Feb;6(1-2):52-8.

Després JP. The endocannabinoid system: a new target for the regulation of energy balance and metabolism. Crit Pathw Cardiol. 2007 Jun;6(2):46-50.

Rosenson RS. Role of the endocannabinoid system in abdominal obesity and the implications for cardiovascular risk. Cardiology. 2009;114(3):212-25.

Di Marzo V, Piscitelli F, Mechoulam R. Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb Exp Pharmacol. 2011;(203):75-104.

Liu B, Song S, Jones PM, Persaud SJ. GPR55: from orphan to metabolic regulator? Pharmacol Ther. 2015 Jan;145:35-42.

Farrimond JA, Whalley BJ, Williams CM. Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology (Berl). 2012 Sep;223(1):117-29.