Endocannabinoid System - Literature Review

Louis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness Institute Louis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness Institute Adjunct Clinical Lecturer – Indiana University School of Medicine

Department of PsychiatryFunctional & Integrative Medicine – Evansville, Indiana

The Encocannabinoid System:A Review of the Literature

October 19, 2017 – Evansville Central Library

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

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

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

4,336 citations as of 12/18/2017

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

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

•

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

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.

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.

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.

But what happens if you don’t make enough???

56 citations 12 18 2017

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.

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.

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.

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.

BThese 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.

BThese 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.

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.

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.

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.”

Source: PLOS One. 2011: 6(12); e28668. Free article online here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/

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.

Micellation

Hemp oil and Ultracell

Full Spectrum Hemp Oil

NOT just CBD…

• Cannabinoids

• Terpenes

• Flavonoids

• Fatty Acids

• Vitamins

• Minerals7

Legal in Indiana

Personal collection Louis B. Cady,

M.D.