1.
Louis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness InstituteLouis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness Institute
Adjunct Clinical Lecturer – Indiana University School of Medicine
Department of Psychiatry
Functional & Integrative Medicine – Evansville, Indiana
The Encocannabinoid System:
A Review of the Literature
October 19, 2017 – Evansville Central Library

2.
H - 2
“There are two objects of medical education: to heal
the sick and to advance the science.”
- Dr. Charles H. Mayo, MD
“The glory of medicine is that it is always moving
forward, that there is always more to learn.”
- Dr. William J. Mayo

3.
Hemp
• One of the oldest known cultivated plants
• 12,000 years of usage
• Used for clothes, soap and rope
• Has a wide array of nutrients in
it of almost all sources.
• Medicinal use: 6,000 years
• 3rd
most prescribed medicinal agent for 60 years
prior to its prohibition in 1937

4.
Purdue University & Mr. Fred A. Miler, botanist to Eli Lilly
& Co. partner for “medicinal extract of Hemp (CBD)
Research,” c. 1912-13

5.
4,336 citations as of
12/18/2017

6.
Endocannibinoid system – the body’s
primary tool of homeostasis
• Most significant neurotransmitter
system in the body
• Regulates & balances:
– Nerve function, stress recovery,
inflammation levels, immune
function, energy intake and storage,
cell life-
cycles/apoptosis/reproduction,
circulatory ystem

7.
Endogenous cannabinoids
• Synthesized in OUR body: ENDOcannabinoids
– 2-AG (2-arachidonylgylerol)
– Anadamide (N-arachidonoylethanolamine “AEA”)
• These are fatty acid neurotransmitters
• 2-AG – most abundant endocannabinoid in the
body
• Regulates appetite, immune function, pain signals,
energy storage, among others

8.
The endocanninoid receptors by the
numbers…
• CB1
– Brain spinal cord, reproductive & connective tissues
• CB2
– Modulates immune system. Found on spleen, tonsils,
thymus, all white blood cells (receptors)
• T cells, B-eta cells, macrophages
• GPR55 – linked to bone development and cancer
cell proliferation

9.
Endocannabinoids 101
• YOU make ENDO-cannabinoids
– 2-AG (2 arachidonoylglycerol)
• Most abundant
• Regulates appetite, immune function, pain signals, energy
storage.
– Anandamide (N-arachidonoylethanolamine “AEA”)
• HEMP plant makes PHYTO-cannabinoids
– Interacts well with human CB receptors.

10.
CECD: Clinical endocannabinoid
deficiency
• Implicated in many hard-to-treat disease
states:
– Fibromyalgia
– Chronic migraines
– Depression/anxiety
– Irritable bowel syndrome
Russo EB. Neuro End Lett
2008 April; 29(2): 192-200.

11.
Anandamide
• From Sanskrit for “bliss” or “happiness.”
• Regulates pleasurable activities – food intake,
reproduction, sleep, and pain relief
• Found in mother’s milk, chocolate, and release
during ovulation
• Produced during meditation, yoga, and causes
RUNNER’S HIGH.
• A “bridge” between mind and body.

12.
But what happens if you don’t make
enough???
56 citations 12 18 2017

13.
B
“Endocannabinoid deficiency syndrome” – 2001
•“In certain conditions, whether congenital or
acquired, endocannabinoid tone becomes deficient and
productive of pathophysiological syndromes.”
•many brain disorders are based on deficient
neurotransmitters.
“Endocannabinoid deficiency syndrome” – 2001
•“In certain conditions, whether congenital or
acquired, endocannabinoid tone becomes deficient and
productive of pathophysiological syndromes.”
•many brain disorders are based on deficient
neurotransmitters.

14.
Inflammation and CBD
• CBD tested on mice that had a
version of RA
– CBD reduced mouse inflammation
by 50% at correct dosage
– Malfait AM et al. The nonpsychoactive cannabis
constituent cannabidiol is an oral anti-arthritic
therapeutic in murine collagen- induced arthritis.
PNAS vol 97 no 17, 9561-9566
• one dosage of CBD immediately
following a heart attack can reduce
infarct size by c. 66%
– Durst R et al. Am J Physiol Heart Circ
Physiol.2007Dec;293(6): H3602-7.

15.
Bluett RJ. Central anandamide deficiency predicts stress-induced
anxiety: behavioral reversal through endocannabinoid
augmentation.
Transl Psych 2014 Jul 8;4:e 408
• Pharmacological augmentation of central endogenous
cannabinoid (eCB) signaling may be an effective
therapeutic strategy to mitigate the adverse behavioral
and physiological consequences of stress.
• These studies provide further support that eCB-
augmentation is a viable pharmacological strategy
for the treatment of stress-related neuropsychiatric
disorders.
• Pharmacological augmentation of central endogenous
cannabinoid (eCB) signaling may be an effective
therapeutic strategy to mitigate the adverse behavioral
and physiological consequences of stress.
• These studies provide further support that eCB-
augmentation is a viable pharmacological strategy
for the treatment of stress-related neuropsychiatric
disorders.

16.
B
CONCLUSIONS:
Our findings demonstrate that the deletion of
Dagla [dacylgerol lipase alpha (DAGLalpha)]
adversely affects the emotional state of animals
and results in enhanced anxiety, stress, and fear
responses.
CONCLUSIONS:
Our findings demonstrate that the deletion of
Dagla [dacylgerol lipase alpha (DAGLalpha)]
adversely affects the emotional state of animals
and results in enhanced anxiety, stress, and fear
responses.

17.
B
These data suggest that anandamide blocks
human breast cancer cell proliferation
through CB1-like receptor-mediated
inhibition of endogenous prolactin action
at the level of prolactin receptor.
These data suggest that anandamide blocks
human breast cancer cell proliferation
through CB1-like receptor-mediated
inhibition of endogenous prolactin action
at the level of prolactin receptor.

18.
B
These data suggest that anandamide blocks
human breast cancer cell proliferation
through CB1-like receptor-mediated
inhibition of endogenous prolactin action
at the level of prolactin receptor.
These data suggest that anandamide blocks
human breast cancer cell proliferation
through CB1-like receptor-mediated
inhibition of endogenous prolactin action
at the level of prolactin receptor.

19.
B
Both endocannabinoids exhibited
neuroprotective activity at LOWER dose,
but were neurotoxic at higher dose.
Both endocannabinoids exhibited
neuroprotective activity at LOWER dose,
but were neurotoxic at higher dose.

20.
B
CONCLUSIONS. This data shows that acute
administration of CBD reduces resting BP and
the BP increase to stress in humans,
associated with increased HR.
CONCLUSIONS. This data shows that acute
administration of CBD reduces resting BP and
the BP increase to stress in humans,
associated with increased HR.

21.
B
“…due to its interaction with PPAR-
gamma, CBD was observed to stimulate
hippocampal neurogenesis.”
“…due to its interaction with PPAR-
gamma, CBD was observed to stimulate
hippocampal neurogenesis.”

22.
Source: PLOS One. 2011:
6(12); e28668.
Free article online here:
https://www.ncbi.nlm.nih.gov/pmc/ar

23.
Bioavailability problems of
commercial products
• Commercial hemp oil
– Not THC free.
– Only 6% of what is ingested gets absorbed.
– 90% is wasted.
• Micellized hemp oil = 85% bioavailability
– Onset of action drops from 1-2 hours down to 5
– 15 min.

24.
Micellation

25.
Hemp oil and
Ultracell

26.
Full Spectrum Hemp Oil
NOT just CBD…
• Cannabinoids
• Terpenes
• Flavonoids
• Fatty Acids
• Vitamins
• Minerals
7

27.
Legal in Indiana

28.
Personal collection
Louis B. Cady,