In this presentation, Dr. Cady reviews the peer-reviewed medical literature for the endocannibinoid system, the concept of endocannibinoid deficiency syndrome (now well established), and citations dealing with the multiplicity of health conditions for which a full spectrum hemp oil should be considered as a reasonable supportive strategy. The difference between the generic "CBD Oil" that is available at health food stores compared to the Zilis products is touched on. The Zilis products appear to have better absorbability, faster onset of action, and scientific studies elucidating the true duration of action of CBD levels in blood serum. This presentation was given to a very appreciative audience at the Friendship Church in Lebanon, TN (a suburb of Nashville).

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
Hemp Oil: What Can It Do For You?
April 6, 2018

4. Disclaimer: Zilis full spectrum hemp
oil is not FDA approved for the
diagnosis, treatment, prevention, or
cure of ANY disease or “medical
condition.”
This type of non-THC containing hemp oil MAY
be appropriate to support the structure and
function of the human body.

5. 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

6. 4,382 results – Feb 2, 2018 6:26 am4,382 results – Feb 2, 2018 6:26 am

7. 2/3/18 - 57 already
*
Search on “endocannabinoid system” www.pubmed.gov March 4, 2018
3/4/2018 - 103
4,417 citations as of 3/4/18
4/6/2018 - 130

8. Study: evaluate CB1 ligands + other agents “that possess
antidepressant potential.”
CONCLUSIONS: “The simultaneous modulation of the
cannabinoid system and supplementation of magnesium
or zinc produce at least additive antidepressant-like
effect.”
Study: evaluate CB1 ligands + other agents “that possess
antidepressant potential.”
CONCLUSIONS: “The simultaneous modulation of the
cannabinoid system and supplementation of magnesium
or zinc produce at least additive antidepressant-like
effect.”

9. The results of the present study suggest that CB1r, CB2r,
and MAGL are closely related to the neuropathological
processes of PD. Therefore, the pharmacological
modulation of these targets could represent a new
potential therapeutic tool for the management of PD.
The results of the present study suggest that CB1r, CB2r,
and MAGL are closely related to the neuropathological
processes of PD. Therefore, the pharmacological
modulation of these targets could represent a new
potential therapeutic tool for the management of PD.

10. Smith SC. Neuro Endocrinol Lett.
2014;35(3):198-201.
Smith SC. Neuro Endocrinol Lett.
2014;35(3):198-201.
CONCLUSION:
Subsequent research has confirmed that underlying endocannabinoid
deficiencies indeed play a role in migraine, fibromyalgia, irritable
bowel syndrome and a growing list of other medical conditions.
Clinical experience is bearing this out. Further research and especially,
clinical trials will further demonstrate the usefulness of medical
cannabis. As legal barriers fall and scientific bias fades this will
become more apparent.
CONCLUSION:
Subsequent research has confirmed that underlying endocannabinoid
deficiencies indeed play a role in migraine, fibromyalgia, irritable
bowel syndrome and a growing list of other medical conditions.
Clinical experience is bearing this out. Further research and especially,
clinical trials will further demonstrate the usefulness of medical
cannabis. As legal barriers fall and scientific bias fades this will
become more apparent.

11. SEVERAL INTERVENTIONS UPREGULATE THE ECS
SYSTEM:
•Analgesics, anti-inflammatories
•Antidepressants, antipsychotics, anxiolytics,
anticonvulsants
•Massage and manipulation
•Acupuncture
•Dietary supplements and herbal medicines.
SEVERAL INTERVENTIONS UPREGULATE THE ECS
SYSTEM:
•Analgesics, anti-inflammatories
•Antidepressants, antipsychotics, anxiolytics,
anticonvulsants
•Massage and manipulation
•Acupuncture
•Dietary supplements and herbal medicines.
McPartland JM et al. PLoS One.
2014, Mar 12;9(3):e89566
McPartland JM et al. PLoS One.
2014, Mar 12;9(3):e89566

12. Getting high on cannabis makes you less likely to work hard for
money, study says – The Independent Sept 1, 2016
http://www.independent.co.uk/news/science/cannabis-marijuana-
weed-effects-getting-high-working-hard-money-motivation-
a7220441.html

13. Way back in April 14-15, 1912

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

17. 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

18. 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

19. 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

20. 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.

23. • Circulating eCB’s in humans, dogs, and ferrets measured
before and after treadmill exercise.
• “We show that humans and dogs shaire significantly
increased exercise-induced eCB signaling following high-
intensity endurance running.
• eCB’s are “a neurobiological reward for endurance
exercise.”

24. 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.

25. 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.

26. But what happens if you don’t make
enough???
57 citations 03 04 2017

27. 57 citations 04/06/ 2017“Deficits in signaling mediated by the
endocannabinoid 2-AG have been reported in
mouse models of autism spectrum disorder.”
“Deficits in signaling mediated by the
endocannabinoid 2-AG have been reported in
mouse models of autism spectrum disorder.”
“Deficits in social interaction, excessive
grooming, decreased exploration of
environment...”
“Deficits in social interaction, excessive
grooming, decreased exploration of
environment...”
“MOA” – “increased glutamatergic drive,
which is consistent with a loss of retrograde
feedback inhibition.”
“MOA” – “increased glutamatergic drive,
which is consistent with a loss of retrograde
feedback inhibition.”

28. 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.

29. 19 results April 5, 201819 results April 5, 2018
• Stimulating ECS:
• Reduction in alcohol consumption with +ECS input
• Antihyperalgesic activities of EC in Mouse Model of
neuropathic pain
• Effects in migraine, fibromyalgia, irritable bowel, and
“other treatment-resistant syndromes” (Russo EB, 2016)
• CB2 deficient mice have pro-inflammatory obesity
• Stimulating ECS:
• Reduction in alcohol consumption with +ECS input
• Antihyperalgesic activities of EC in Mouse Model of
neuropathic pain
• Effects in migraine, fibromyalgia, irritable bowel, and
“other treatment-resistant syndromes” (Russo EB, 2016)
• CB2 deficient mice have pro-inflammatory obesity

30. “Ethan B. Russo's paper of December 1, 2003
explored the concept of a clinical endocannabinoid
deficiency (CECD) underlying the pathophysiology of
migraine, fibromyalgia, irritable bowel syndrome and
other functional conditions alleviated by clinical
cannabis.”
“Ethan B. Russo's paper of December 1, 2003
explored the concept of a clinical endocannabinoid
deficiency (CECD) underlying the pathophysiology of
migraine, fibromyalgia, irritable bowel syndrome and
other functional conditions alleviated by clinical
cannabis.”“Subsequent research has confirmed that underlying
endocannabinoid deficiencies indeed play a role in
migraine, fibromyalgia, irritable bowel syndrome and
a growing list of other medical conditions.”
“Subsequent research has confirmed that underlying
endocannabinoid deficiencies indeed play a role in
migraine, fibromyalgia, irritable bowel syndrome and
a growing list of other medical conditions.”
Smith SC, Wagner MS. Neuro Endocrinol Letter. 2014;35(3):198-201.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.”

37. What does the literature say about…
• Pain
• Sleep
• Anxiety
• Seizures
• IBS
• ADHD

38. “Endocannabinoids, a group of less well--known endogenous bioactive lipids ... [are]
able to influence both inflammation and pain.”

39. • are under circadian control
• promote non-rapid eye movement sleep
• promote REM by interacting with melanin-
concentrating hormone neurons
• restores sleep in a model of insomnia in rats
Endocannabinoids sleep – 102 citations 3/4/2018

40. • cannabidiol (CBD), while representing a less
specific pharmacological approach, may be another
way to modulate eCBs and interacting
neurotransmitter systems to alleviate anxiety.
Endocannabinoids anxiety– 306 citations 3/4/2018

41. 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.

42. Seizures
“These data suggest the need for developing novel
treatments using compounds that selectively target
individual elements of the endocannabinoid signaling
system.
“These data suggest the need for developing novel
treatments using compounds that selectively target
individual elements of the endocannabinoid signaling
system.
86 citations on “endocannabinoid system epilepsy” – 3/4/2018alsdkfj

43. Endocannabinoid system and IBS
Hasenoehri C et al. The gastrointestinal tract – a central organ of
cannabinoid signaling in health and disease. Neurogastroenterol.
Motil. 2016 Dec; 28(12):1765-1780.
“Cannabinoid receptors and their
endogenous ligands, the endocannabinoids,
participate in the regulation of GI motility,
secretion, and the maintenance of the
epithelial barrier integrity.”
“Cannabinoid receptors and their
endogenous ligands, the endocannabinoids,
participate in the regulation of GI motility,
secretion, and the maintenance of the
epithelial barrier integrity.”
Endocannabinoid system irritable bowel syndrome
– 26 citations - March 4, 2018

44. ADHD & the Endocannabinoid System
• 18 citations in literature – March 4, 2018
– “adults with ADHD may represent a subgroup of
individuals who experience a reduction of
symptoms and no cognitive impairments
following cannabinoid use.”
• Cooper RE et al. Eur Neuropsychopharmacol. 2017
Aug; 27(8):795-808

45. • 30 adults with ADHD, placebo controlled study
• Sativex Oromucosal spray was used.
• “Adults with ADHD may represent a sub-group of
individuals who experience a reduction of
symptoms and no cognitive impairments following
cannabinoid use.”

46. 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.

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

48. Micellation

49. Hemp oil and
Ultracell

50. Legal in Indiana

51. Legal in Indiana

52. 50% absorption to average plasma
level within 15 minutes.

53. New Ultracell Study
• N = 20
• Up to 94% absorption of cannabinoids in 12 hours
– 10.9 mg of CBD in Ultracell
– - 8.3 mg back in the blood
• Blood drawn every 15 minutes and then hourly out to 11 hours
• 50% OF ULTRACELL was in the body in 10 – 15
min

55. • 2000 inappropriate online
health claims; 1000 still
online
• www.truthinadvertising.org ,
2017
• 158 direct selling companies
• 62 sell nutritional supplements
• 60/62 (97%) have made health
claims that...
• “their products can diagnose,
treat, cure, prevent, or alleviate
the symptoms of and/or reduce
the risk of developing a
multitude of diseases.”
The Bottom Line: DON’T MAKE UNSUBSTANTIATED
“HEALTH CLAIMS.”

56. Personal collection
Louis B. Cady,

57. Contact information and slide resources
Louis B. Cady, MD
Cady Wellness Institute
4727 Rosebud Lane – Suite F
Newburgh, IN 47630 USA
Office (812) 429-0772
• www.cadywellness.com
• info@cadywellness.com
• www.facebook.com/cadywellnes
• Twitter: @LouisCadyMD