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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