Clinical Endocannabinoid Deficiency (CECD) Disease

The deficiency of the endocannabinoid system is characterized by different symptoms including, but  not limited to pain, nausea, migraines, diseases like fibromyalgia, colitis, irritable bowel syndrome, among others. In this analysis, I will first characterize this “new” disorder or disease based on a deficiency of cannabinoids activation (Section A) and thereafter, i will examine what responsible health professionals can recommend to better optimize this bodily function we call ECS or endocannabinoid system (Section B)

Section A

A new Disease for an old Reality: Cannabinoid deficiency

In the same way that the lack of vitamin C will lead to scurvy, lack of vitamin D to rickets and lack of vitamin B to dementia, inter alia, in the same way, the lack of cannabinoid activation will lead to many diseases of disharmony, inflammation, pain, lack of coordination, frustation and entropy, all of which favor the predatory narcissistic behavior that is so prevalent among those who choose to grab the high-paying power jobs in politics, law and even in conventional medicine and corporate pharmaceutical scientism-based “witchcraft” (i.e. in the Bible, pharmaceutical notion means witchcraft, but witchcraft in the evil sense).

“Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines” (Source)

Cannabinoid therapy can even help with one of today’s major public health challenge, leaky gut or intestinal permeability, an important condition that has been linked to over 80 auto-immune diseases.

“These findings suggest that locally produced endocannabinoids, acting via CB1 receptors play a role in mediating changes in permeability with inflammation, and that phytocannabinoids have therapeutic potential for reversing the disordered intestinal permeability associated with inflammation”. (Source)

Furthermore, the activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion, and intestinal motility. These findings suggest that endocannabinoids may play a role in modulating intestinal permeability and that plant-derived cannabinoids, such as THC and CBD, may have therapeutic potential in conditions associated with abnormally permeable intestinal epithelium.

What are Cannabinoids ?

Cannabinoids are compounds derived from Cannabis sativa (phytocannabinoids) or produced endogenously in the body (endocannabinoids). The most prevalent phytocannabinoids include Δ9-tetrahydrocannabinol (THC), the psychotropic constituent of Cannabis, and cannabidiol (CBD), which lacks psychoactivity. Cannabinoids act through at least two cloned G protein-coupled receptors: the CB1 receptor (Matsuda et al., 1990) and the CB2 receptor (Munro et al., 1993). The discovery of endogenous ligands, such as anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), indicate the presence of a functional “endocannabinoid system” (for a recent review of endocannabinoid pharmacology, see Reggio, 2010). Cannabinoids also activate transient receptor potential vanilloid subtype 1 (TRPV1; Zygmunt et al., 1999), peroxisome proliferator-activated receptors (PPARs) (O’Sullivan, 2007), the orphan receptor GPR55 (Baker et al., 2006), and as yet uncloned cannabinoid receptors (Breivogel et al., 2001; Begg et al., 2005).

The presence the endocannabinoid system has been identified in the gut. In 1995, 2-AG was isolated in the canine intestine (Mechoulam et al., 1995), and in 2001, AEA was identified in the rat small bowel (Izzo et al., 2001). CB1 receptors have been shown to be located in the gastrointestinal tract of many species, including rats, guinea pigs, and humans (Croci et al., 1998; Kulkarni-Narla and Brown, 2000; Coutts et al., 2002; Casu et al., 2003). Immunohistochemical studies indicate that the enteric nervous system appears to be the main site of action for cannabinoids in the gastrointestinal system. (Source)

Cannabinoid Deficiency Disease is Real

The evidence shows that someone with an underactive cannabinoid system will not get the same rewarding aspects of food and other sensuous experience. They will be more anxious and more likely to have food sensitivities, because the cannabinoid system is very important for emotional balance and creating tolerance to our environment, especially food that interact with our gut.

Those suffering from Cannabinoid Deficiency tend to be  predisposed to an autoimmune condition, especially one involving the gut. Because the cannabinoid system is very highly concentrated in the hypothalamus, basal ganglia and the hippocampus, which are part of the limbic system, a Cannabinoid deficient person will also be prone to more emotional insanity in his or her life. These people will not get hungry very often and more likely eat to get energy.  When they do eat, they will be more likely to burn it and not as fat.  This is from a dysfunctional cannabinoid system. Blocking the CB1 receptors increases insulin sensitivity and the burning of fatty acids in muscles and the liver (Source).

Clinical observation confirms that Cannabinoid Deficient patients tend to have higher adiponectin, higher growth hormone (cannabinoids inhibit growth hormone release (Source), lower triglycerides, higher HDL, lower insulin resistance, lower CRP and higher TSH, but not higher T4/T3 (cannabinoids decrease TSH Source). Cannabinoid deficient people also tend to suffer from hyper-algesic syndromes, meaning that there’s seems to be pain out of proportion to what should be going on.

 

“Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines”. (Source) (1)

A review of the literature indicates that significant progress has been made since Dr. Ethan B. Russo’s landmark paper, just ten years ago (February 2, 2004). Investigation at that time suggested that cannabinoids can block spinal, peripheral and gastrointestional mechanisms that promote pain in headache, fibromyalgia, irritable bowel syndrome and muscle spasm. Today, much more has been discovered.

“Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially, clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.” (Neuro Endocrinol Lett. 2014;35(3):198-201)

Case in Point: the Microbiome

The Microbiome  plays a leading role in the opening/closing of the tight junctures. It acts a gatekeeper – an intestinal bouncer who screens ingested particles and either permits or denies their entry. However, when the microbiome becomes depleted in diversity and density, then this condition can result from the Clinical Cannabinoid Deficiency Syndrome that can promote an imbalance Microbiome, one consequence of which is that the Microbiome becomes overgrown with pathogenic microorganisms that take charge. When they  produce an Endotoxin known as Lipopolysaccharide (LPS) within their cell walls, the conditions of health worsen. Additionally, LPS causes damage to the Enterocytes through inflammation. Not ideal as this further increases the distance of the tight junctures. The binding of LPS triggers the release of Pro-Inflammatory Cytokines TNF-alpha, IL-1beta, IL-6. Inflammation of the gut wall causes it to take on damage, reducing its structural integrity. (2)

Not surprisingly, Cannabinoids THC and CBD interact with the same Cannabinoid receptors in the gut. These engage membrane proteins, which alters intestinal permeability. Specifically, THC and CBD were found to increase the expression of the membrane protein Zonula occludens-1 ZO-1, decreasing gut permeability. This effect was a result of CB1 Receptor antagonism.  
It is possible that CBD was responsible for this effect as it is a partial CB receptor antagonist. An antagonist suppresses action of receptor. Whereas THC is a partial agonist – activates action of receptor.  This is good news because decreases in intestinal permeability help to patch the holes in a leaky gut. Through regulating tight juncture function, cannabinoids may help prevent food particles, infections, and other inflammatory products from entering the bloodstream. This means that inflammation can be reduced, preventing further damage to the gut wall.” (3)

Furthermore, chronic inflammation in the gut progressively damages Enterocyctes, which exposes gaps in the gut wall. This is how increases in intestinal permeability occur. Cannabis is a well known anti-inflammatory, arguably one of its most well known properties and can significantly contribute in putting out the “fire”.

An exciting study found Cannabinoids THC and CBD to be effective in reversing disordered intestinal permeability induced by inflammation. Specifically, the inhibition of inflammatory cytokines IFNγ and TNFα by THC and CBD protected against gut wall damage, sparing permeability. The anti-inflammatory effect by THC and CBD occurred through action on the CB1 receptor. Interestingly, another study showed a reduction in LPS induced inflammation via CB2 receptor activation in mice. This finding was also demonstrated in LPS induced pulmonary inflammation in mice. In the later study, the reduction in inflammation was in part due to CB2 receptor activation via THC, which effectively reduced levels of TNFα. These findings suggest that LPS induced inflammation (endotoxin released from gram negative bacteria) could be addressed with the therapeutic action of THC.

Cannabinoids and other plant constituents of Cannabis have also shown promise as antibacterial agents. This is especially important because antibacterial herbs can influence the composition of the microbiome and the health of this microbial community is the first thing to focus upon.

A study investifgated the antimicrobial activity of essential oils made from Hemp. One particular preparation of Hemp oil, Futura, was capable of inhibiting the growth of all Gram + and Gram – Bacteria tested in addition to partially controlling yeasts. The beneficial action of the essential oil preparation was a combined action of Cannabinoids, Terpenoids, Flavinoids and Cannabinoid precursors.  Another study found similar results. Polyphenols extracted with alcohol from Hemp were found to exert potent antimicrobial activity on S. aureus (Gram +ve), P. aeruginosa (Gram -Ve), and C. albicans (yeast). In addition, Marijuana derived Cannabidiol (CBD), Cannabichromene (CBC), Cannabigerol (CBG), ∆9-tetrahydrocannabinol (THC) and Cannabinol (CBN) all exert antibacterial activity. (Source)

In light of the combined action of plant constituents of Cannabis on microorganisms; It may be effective to use cannabis as a whole plant extract.

Reference and Precision Notes

(1). Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? [Neuro Endocrinol Lett. 2004] (Neuro Endocrinol Lett. 2008 Apr;29(2):192-200.) (Source)
(2). The gut wall is much like passport control at the airport, and the Enterocytes the booths which allow passengers to pass through. When passport officers occupy the booths, people get checked to ensure they are who they claim to be. They pose no potential threat. With damaged enteroctyes, picture a few vacant booths. Say some passport officers are on a break. This leaves a few booths open to suspect individuals to sneak through.  Once suspect individuals sneak through passport control, they go on to board a flight. Imagine that a suspect boarding a flight is like a pathogen hitching a ride in the bloodstream.The flight will provide transport to other countries, which you can think of as various organs in the body. These suspects can go on to conduct acts of terror in other countries. This is much like the Inflammation induced by LPS and other antigens on organs in the body.In the development of Autoimmune disease this is what happens. Subsequently causing a confused immune system to attack healthy tissues and organs in the body in an attempt to deal with invaders. All this from a Leaky Gut.
(3).  CANNABIS AND CANNABINOID RESEARCH, 2016, published by Mary Ann Liebert, Inc., New Rochelle, NY

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