The Human Endocannabinoid System Meets the Inflammatory Cytokine Cascade
By: Dennis Hill
The Endocannabinoid System (ECS) started revealing itself to researchers in the
1940s and by the late '60s the basic structure and functionality had been laid
out. Today we know the ECS is a comprehensive system of biochemical modulators
that maintain homeostasis in all body systems including the central and
peripheral nervous systems, all organ systems, somatic tissues, and all
metabolic biochemical systems, including the immune system.
This homeostatic matrix is not a recent evolutionary twist just for humans; we
Find the Endo cannabinoid System in every chordate creature for the last 500
million years. It is a fully mature biochemical technology that has maintained
health and metabolic balance for most of the history of life itself.
The two major interactive systems within the ECS are (1) the cannabinoid
receptors that we find on all cell surfaces and neurological junctions and (2)
the endocannabinoids that hit the receptors to trigger various metabolic
processes. Looking at a cannabinoid receptor distribution map we see that CB1
receptors, that are most sensitive to anandamide, are found in the brain, spinal
nerves, and peripheral nerves. CB2 receptors preferred by 2-arachidonoylglycerol
(2-AG) are found largely in the immune system, primarily the spleen. A mix of
CB1 and CB2 receptors are found throughout the rest of the body including the
skeletal system. And yes, 2-AG or CBD will grow new trabecular bone.1 It is also
useful to note that both anandamide and 2-AG can activate either CB1 or CB2
receptors.
The nature of the endocannabinoids are functionally much like neurotransmitters,
but structurally are eicosanoids in the family of signaling sphingolipids. These
signaling cannabinoids keep track of metabolic systems all over the body. This
information is shared with the nervous system and the immune system so that any
imbalance is attended to. If the body is in chronic disease or emotional stress,
the immune system can fall behind and lose control of compromised systems. It is
here that phytocannabinoids can pitch in to support the stressed body in a
return to health. The cannabis plant provides analogues of the body's primary
signaling cannabinoids. Tetrahydrocannabinol (THC) is mimetic to anandamide, and
cannabidiol (CBD) is mimetic to 2-AG, and has the same affinity to CB1 and CB2
receptors; providing the body with additional support for the immune and
endocannabinoid systems.
Phytocannabinoids supercharge the body's own Endocannabinoid System by amping up
the response to demand from the immune signaling system in two modes of
intervention: one, of course, is in bonding with the cannabinoid receptors; the
other is in regulation of innumerable physiological processes, such as
cannabinoid's powerful neuroprotective and anti-inflammatory actions, quite
apart from the receptor system. It is interesting to note here that the
phytocannabinoids and related endocannabinoids are functionally similar, but
structurally different. As noted above, anandamide and 2-AG are eicosanoids
while THC and CBD are tricyclic terpenes.
Let us look more closely at the two primary therapeutic cannabinoids, THC and
CBD. The National Institutes of Health tell us that THC is the best known
because of its signature psycho- tropic effect. This government report shows THC
to be effective as an anti-cancer treatment, an appetite stimulant, analgesic,
antiemetic, anxiolytic, and sedative.2
CBD (cannabidiol) is a metabolic sibling of THC, in that they are alike in many
ways but are also different in important properties. First we see that CBD has
no psychotropic effects and there are few CB2 receptors in the brain and
peripheral nerves. There appears to be a broader therapeutic profile associated
with CBD, which is listed here:
One of the most important health benefits of cannabinoids is their
anti-inflammatory property. In this, they are strong modulators of the
inflammatory cytokine cascade. Numerous disease states arise out of chronic
inflammation; such as, depression, dementias including Alzheimer's, cancer,
arthritis and other autoimmune disorders, viral infection, HIV, brain injury,
etc.
Inflammatory cytokines can be activated by oxidative stress and disease states.
Cannabinoids, being immunomodulators interrupt the cytokine inflammatory cascade
so that local inflammation does not result in tissue pathology. Thus we are
spared morbid or terminal illnesses.4
If our own endocannabinoid system can maintain metabolic homeostasis and even
cure serious disease, why are we plagued by illness? We know that the body
produces only small amounts of anandamide and 2-AG; enough to maintain the body
but not enough to overcome chronic stress, illness, injury, or malnutrition.
Cannabis is the only plant we know of that produces phyto- cannabinoids that
mimic our own endocannabinoids. One of the great benefits of this mimetic
medicine is that cannabinoids are essentially natural to our biology and do no
harm to our tissues and systems.
It is well known that most diseases of aging are inflammatory in origin, thus
making cannabis the best anti-aging supplement we could take to avoid arthritis,
dementia, hypertension, diabetes, osteoporosis, and cancer. This is our key to
good health and long life.
Since it is such an important attribute, as well as being independent of the
cannabinoid receptor system, let's look a little deeper into the ability of
cannabinoids to inhibit the inflammatory cytokine cascade. Inflammation is good
for us, a little here, a little there; it brings T-cells and macrophages to
infection sites. This is good. However, chronic inflammation can cause serious
illness and death. How do phytocannabinoids rescue us from dreaded infirmities?
When the call comes in to the immune system to send troops, the First thing to
happen is that the immune system signals glial cells to produce cytokines. Once
this cat is out of the bag, the process can go one of two ways.
A) Killer cells clean up the infection and all is well.
B) Cytokines can stimulate more cytokine production and cause many more cytokine
receptors to awaken. Unchecked, this becomes a cytokine storm showing symptoms
of swelling, redness, fatigue, and nausea; even death.
Phytocannabinoids have the ability to suppress this inflammatory cytokine
cascade by inhibiting glial cell production of the cytokines interferon or
interleukin. Here we see the seeds of chronic inflammation dissolved by the
modulation process of cannabinoids bringing homeostasis to systems out of
balance. This is a good example of how cannabinoids normalize biological
processes all throughout the body and allows us to keep that glow of well-being
through a long and happy lifetime.
-Dennis Hill
References:
1.
http://www.pnas.org/content/103/3/696
2.
http://www.cancer.gov/cancertopics/pdq/cam/cannabis/healthprofessional/page1
3.
http://cannabisinternational.org/info/Non-Psychoactive-Cannabinoids.pdf
4.
http://www.ncbi.nlm.nih.gov/pubmed/16918439
http://cannabisnationradio.com/dennis-hill-endocannabinoid-system