Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes

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“Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin. Its base hypothesis is that all humans have an underlying endocannabinoid tone that is a reflection of levels of the endocannabinoids, anandamide (arachidonylethanolamide), and 2-arachidonoylglycerol, their production, metabolism, and the relative abundance and state of cannabinoid receptors. Its theory is that in certain conditions, whether congenital or acquired, endocannabinoid tone becomes deficient and productive of pathophysiological syndromes. When first proposed in 2001 and subsequently, this theory was based on genetic overlap and comorbidity, patterns of symptomatology that could be mediated by the endocannabinoid system (ECS), and the fact that exogenous cannabinoid treatment frequently provided symptomatic benefit. However, objective proof and formal clinical trial data were lacking. Currently, however, statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder. Additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS.

Various strategies to treat CED conditions are possible. A direct approach with CB1 agonists must recognize the fact that the ECS operates as a homeostatic regulator that sometimes requires a gentle pharmacological nudge, rather than a forceful shove, by synthetic full agonists. Thus, small doses of a weak partial agonist (e.g., THC) should be considered, which would not induce tolerance and may jump-start the ECS. Even THC alone is poorly tolerated or appreciated by patients,98 and standardized whole cannabis extracts that contain additional synergistic and buffering components, such as CBD and cannabis terpenoids, are certainly preferable.93 Alternatively, FAAH inhibitors will also raise AEA levels, but only CBD among them has achieved current legal commercial market availability. Pharmaceutical approaches affecting endocannabinoid transport or its genetic regulation would also hold promise. Beyond drug interventions, a growing body of knowledge supports the realistic goal that lifestyle approaches should be integral to the treatment of CED; specifically, low-impact aerobic regimens have demonstrated beneficial effects on endocannabinoid function,99 and as discussed above, dietary manipulations with probiotics and prebiotics may ameliorate not only IBS symptoms but also the entire spectrum of CED conditions. Ultimately, multimodality approaches are most likely to be fruitful in treatment of these common yet difficult clinical challenges.

http://online.liebertpub.com/doi/pdf/10.1089/can.2016.0009

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Fetal Syndrome of Endocannabinoid Deficiency (FSECD) In Maternal Obesity.

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“The theory of a fetal origin of adult diseases links many pathological conditions to very early life events and is known as a “developmental programming” phenomenon. The mechanisms of this phenomenon are not quite understood and have been explained by inflammation, stress, etc. In particular the epidemic of obesity, with more than 64% of women being overweight or obese, has been associated with conditions in later life such as mental disorders, diabetes, asthma, and irritable bowel syndrome.

Interestingly, these diseases were classified a decade ago as Clinical Syndrome of Endocannabinoid Deficiency (CECD), which was first described by Russo in 2004.

Cannabinoids have been used for the treatment of chronic pain for millenniums and act through the mechanism of “kick-starting” the components of the endogenous cannabinoid system (ECS).

ECS is a pharmacological target for the treatment of obesity, inflammation, cardiovascular and neuronal damage, and pain.

We hypothesize that the deteriorating effect of maternal obesity on offspring health is explained by the mechanism of Fetal Syndrome of Endocannabinoid Deficiency (FSECD), which accompanies maternal obesity. Here we provide support for this hypothesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27959272

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Alternative Cannabinoid Dietary Cannabis

“Cannabis has medicinal activity that prevents or treats conditions when included in the diet as an essential food. Cannabinoids are highly available in raw Cannabis juice, sprouts, micro-greens and pure CBD strains.  Cannabis produces each dietary essential we cannot synthesize: non-psychoactive Essential Cannabinoid acids, Essential Fatty acids, Essential Amino acids and fiber.”

 
“The Endo-Cannabinoid System maintains our biological systems by regulating each cell tissue. It uses Arachidonic acid from the Essential Fatty Acid Omega 6 to make Cannabinoids: fatty molecules that communicate harm between cells.
    Dietary Cannabis mimics the Endo-Cannabinoid System by providing “Phyto”-Cannabinoids when there is an Arachidonic acid or Clinical Endo-Cannabinoid Deficiency.
    “The body produces endogenous cannabinoids. You may have heard of endorphins: that’s endogenous morphine. Well, in a similar fashion, the body produces endogenous cannabinoid. ”
    “A million times a day, cells begin to divide that shouldn’t be dividing and the immune system has to say, “Hey, you know, the shrubs are getting a little hairy there; we’ve got to trim them down. We’ve got enough renal cells or kidney cells. We’ve got enough bone cells, muscle cells.” So the immune system’s highly competent at dealing with that, but it can become more competent. And that is exactly what cannabinoids do, whether you’re talking about the body’s endogenous cannabinoids, or the plant, which can be Phyto-Cannabinoids (which just means cannabinoids from plants) or exogenous Cannabinoids. Both of those terms refer to those 20 carbon molecules that are produced outside of the body, but bind to the protein receptors on the cells in our body and therefore help regulate it. So whether we’re talking about the body’s chemistry, or the plant chemistry, their role is to modulate the function of the immune system.”
    “So a cannabinoid is a modulator that restores optimal function. That’s what the body’s system is doing. That’s what the plant does. The plant facilitates the rapid restoration of the normal function.” — William L. Courtney, M.D. “
 
 
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