Understanding Medical Use of Cannabis

Dr. LeTa B. Jussila Doctor of Acupuncture and Oriental Medicine

Anything I say or any products I may recommend in this presentation do not diagnose, cure, treat, heal or prevent any disease or illness.

Overview• History of Cannabis • What is CBD • What is it good for? • How to know what to buy • Who is Prime My Body • Getting Involved & Getting Paid

Brand, E. J., & Zhao, Z. (2017). Cannabis in Chinese Medicine: Are Some Traditional Indications Referenced in Ancient Literature Related to Cannabinoids? Frontiers in Pharmacology, 8, 108. https://doi.org/10.3389/fphar.2017.00108

Portrait of the Red Emperor Shen Nung 2737 BCE Shen Nung prescribed Cannabis tea for gout, rheumatism, malaria and poor memory

The Yellow Emperor, Huang Di 2698-2205 BCE The Yellow Emperor Huangdi wrote the Neijing, which outlines cannabis for certain ailments

flower (hua) root (gen) leaf (ye)

skin (pi) male seed (fen) seed (ren)

Timeline of Key Discoveries8,000+ BCE Use of hemp cord in pottery identified at ancient village site dating back over 10,000 years. Finding hemp use and cultivation in this date range puts it as one of the first and oldest known human agriculture crops. 6,000 BCE Cannabis seeds and oil used for food in China. 4,000 BCE Textiles made of hemp are used in China and Turkestan.

1851: United States Pharmacopeia classified

marijuana as a legitimate medical compound

Victorian-era neurologists used

Indian hemp to treat epilepsy and reported

success

Use diminished with the introduction of

phenobarbital (1912) and phenytoin (1937)

Marijuana Tax Act of 1937

1941: USP/NF Cannabis preparations are removed

from the United States Pharmacopoeia and National Formulary

Controlled Substances Act of 1970: cannabis is labelled as a Schedule 1

substance also with heroin and LSD

1999 Department of Health and Human Services filed a

patent for cannabinoids awarded in 2003 for

“cannabinoids as antioxidants and

neuroprotectants”

Cannabinoid History

Baron EP. Headache. June 2015 Borgelt LM. Pharmacotherapy 2013; 33(2):195-209Friedman D, Devinsky O. N Engl J Med 373; 11

Health Conditions Influenced by Cannabinoids

ADD/ADHD ALS Alzheimer’s Anorexia Anxiety Asthma Ataxia Bipolar Cachexia Cancer Chronic fatigue Chronic pain Cramps Crohn’s

Diabetes Depression Epilepsy Fever Fibromyalgia Glaucoma Hepatitis HIV/AIDS Incontinence Insomnia Migraine MRSA Multiple Sclerosis Nausea

Neuralgia Neuropathy Parkinson's PMS PTSD Rheumatoid Arthritis Seizure disorders Sickle cell anemia Spasms Spinal injury Stroke Tourette’s Vomiting

Kogan NM, Mechoulam R. Cannabinoids in health and disease. Dialogues in Clinical Neuroscience. 2007;9(4):413-430.

Why does one herb help so many

different conditions?

The Endocannabinoid

System

The ECS is believed to have more cellular receptor sites than any other receptor system.

Introduction to the ECSEndocannabinoid System

• Endocannabinoids are neurotransmitters made by the body

• Cannabinoid receptors are found throughout the body (brain, organs, connective tissues, glands, and immune cells)

• Endocannabinoids act as neuromodulators to help the body re-establish homeostasis in response to stress

• Acts as a bridge between body and mind

• Healthy ECS essential for good health

YOUR ENDOCANNABINOID SYSTEM IS INVOLVED IN EVERY ASPECT OF HUMAN HEALTH

Cannabinoid Receptors

Cannabinoid Receptors

Adipose tissue Connective tissue Endocrine glands Exocrine glands

GI tract Heart

Leukocytes Liver Skin

Spleen Testes, uterus

B-cells Macrophages

Monocytes T-cells Liver

Spleen Tonsils

CNS GI tract

How your Endocanabinoid System (ECS) works

Current Research

• Embryonic Development

• Neural Plasticity

• Neuroprotection*

• Immunity

• Inflammation

• Apoptosis*

• Carcinogenesis

• Pain and emotional memory*

• Hunger

• Metabolism

4 Types of Cannabinoids

1. Phytocannabinoids occur in plants, such as Cannabis

2. Endocannabinoids occur naturally in the brain

3. Synthetic cannabinoids are created in laboratories and are not known to exist naturally

4. Cannabimimetic terpenes such as Coneflower (Echinacea), Clove, Black Pepper (hu jiao), Rosemary (mi die xiang), Black Truffles (Tuber melonsporum), Carrot, Chinese Rhododendron (man shan hong), Helichrysum, Flax (ya ma zi), Frankincense (ru xiang), Liverwort, Kava kava, Maca

Cannabinoids - EndogenousAnandamide (AEA)

• Ananda is Sanskrit for Bliss

• CB1 and CB2 agonist

• The first endogenous cannabinoid identified - 1992 by W.A. DeVane in Raphael Mechulaem’s group at Hebrew University, Israel.

• Anandamide also found in chocolate

• Produced by body during meditation

• Part of “Runners High” effect Here

Di Marzo, V. et al. Prostaglandins, Leukotrienes and Essential Fatty Acids , Volume 66 , Issue 2 , 377 - 391

Cannabinoids - Endogenous2-Arachidonoylglycerol (2-AG)

• High levels in CNS (> Anandamide)

• Neuromodulator

• Made from Omega-6 fatty acids

• CB1 and CB2 agonist

• Found in animal milk, including breast milk

• Has a cell membrane transporter system

• Discovered in 1994

Gonsiorek, W., Lunn, C., Fan, X., Narula, S., Lundell, D., & Hipkin, R. W. (2000). Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Molecular Pharmacology, 57(5), 1045–1050.

Cannabinoids - Exogenous

• THC - Psychoactive • CBD -Non-Psychoactive • 160+ types of cannabinoids

Cannabinoids - Exogenous

Cannabis PlantFamily  Cannabaceae – Hemp family

Genus Cannabis L. - hemp

Genus Humulus L. - hops

https://plants.usda.gov/java/ClassificationServlet?source=display&classid=Cannabaceae

Species  Cannabis sativa L. – marijuana

Subspecies  Cannabis sativa L. ssp. indica (Lam.) E. Small & Cronquist – marijuana

Subspecies  Cannabis sativa L. ssp. sativa – marijuana

Entourage EffectSo, cannabis is a botanical. This is a way of saying that it’s a plant-based medicine. And, although the thrust of pharmaceutical development for decades has been on single molecules, often synthetic, this is the more common concept in medicine historically. What I mean is, traditionally people have used plant drugs to treat their problems. It’s only been in the last 75 years there’s been this shift toward synthetics. So, a botanical doesn’t rely on one compound to produce the beneficial effects. Rather there may be many – and that’s certainly the case in cannabis where we know that there are actually over 100 related molecules, we call cannabinoids, but in addition there are aromatic compounds, the same things that you’d find in lemon and pine needles called terpenoids that alter the effects of the cannabinoids in a way that often is synergistic. Synergy is a boosting of effect. So, it would be the idea that 2 + 2, instead to equaling 4, it gives you an 8 in terms of the benefit. So, for example, as we’ve mentioned, cannabidiol treats pain. But there are other ingredients in cannabis that also treat pain or may limit the side effects of other components and so it is sort of like an ensemble of musical instruments where you might think if THC as the soloist with an important part provided by cannabidiol, but you also have these other components producing a harmony that really increases the overall effect and makes hopefully the best possible medicine.

CBD and CBGCannabidiol and Cannabigerol

Cannabidiol

Pain Management Lessens The Risk of Diabetes Helps With Sleep Apnea and Insomnia Effective Against Epilepsy Symptoms Lowers The Risk of Obesity Anxiety and Stress Heals and Protects Your Skin Relief From Arthritis Maintains Brain Health May Help With Substance Abuse Treatment Lowers the Risk of Cardiovascular Disease Helps Achieve Better Cholesterol Levels Helps Curb Your Appetite Reduces The Cancer Risk Alleviates Depression and Mood Disorders

Cannabigerol

Analgesia Antibacterial Anti-convulsive Anti-inflammatory Anti-insomnia Appetite stimulant Anti-proliferative Antidepressant Brain cell stimulant Bone stimulant

Conditions in Clinical Practice Rank in Order of Prescribed - Medical Cannabinoids

• Pain (acute pain, chronic inflammatory, neuropathic, arthritis, fibromyalgia, migraines, etc) • Mental disorders (all kinds, depression, anxiety, stress, PTSD) • Cancers (pain relief, nausea/vomiting from chemo, anti-carcinogenic) • Gastrointestinal disorders • Insomnia • Migraine headaches • Harm reduction, alternative to opioids . . . • Spastic disorders • Autoimmune disorders • Neurodegenerative disorders • Glaucoma • Skin diseases • Seizures, Epilepsy, Autism, Tourettes, ADD, Dystonia, Dementia • AIDS and other infections

Hergenrather 2016

Endocannabinoid Tone

“Clinical Endocannabinoid Deficiency Syndrome” (CEDS) - coined by Dr. Ethan Russo

Causes of poor endocannabinoid tone: • poor diet • lack of exercise • drug abuse • environmental toxins • genetic factors • chronic stress • compromised health

https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2016/NSDUH-DetTabs-2016.htm#tab1-32B

Balance of CB1 & CB2 activity at any given time

Endocannabinoid DeficiencyIn human studies, ECS deficiencies have been implicated in:

– Schizophrenia, uncompensated – Migraine

– Multiple sclerosis – Huntington’s disease – Parkinson’s, uncompensated – Irritable bowel syndrome – “Failure to Thrive” Syndrome – Anorexia, uncompensated – Chronic motion sickness

– Fibromyalgia – Menstrual symptoms

– Seizure disorders

– Mood disorders, depression and happiness(reviewed in McPartland, 2014 and Russo, 2004)

Gene Transcription Modulation

Research Paper: Differential Transcription profiles mediated by exposure to the Cannabinoids, Cannabidiols, D9 THCol in BV2 microglial cells (British Journal of Pharmacology)

Major Effects on Ox Stress, Inflammation, and Immunity Genes

• CBD much broader effect than THC on a transcription level

• Regulates expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation

• 1200+ genes affected by CBD • 680 gene transcripts upregulated

“turned on” • 584 down regulated “turned off”

CBD reduces brain cancer and breast cancer cell proliferation and metastasis by inhibiting the expression of the ID-1 gene. ID-1 expression is implicated in several kinds of aggressive cancer.

NeuroInflammation

• Mercury • Glyphosate • Mold Toxins • Lyme Toxins • EMF Stress • Dysbiotic Toxins

• Toxic metabolites • Autoimmune • Aging • Microbes • Viruses

Direct Neurotoxins (Glutamate Excitotoxins)

• Traumatic brain injury • Spinal cord injury • Air pollution • Passive smoke

GI and Digestion

• International Journal of Eating Disorders

• modulate appetite (munchies); chemo, anorexia, eating disorders

• reduces nausea

• Studies: Crohn’s, Obesity, Diabetes

Liver• Alcohol-induced steatosis

• unregulated antioxidant pathways

• Prevents accumulation of fats and lipids

• Alcohol-induced steatosis, fatty liver

• unregulated antioxidant pathways

• Prevents accumulation of fats and lipids

Pain Management• Study: The Spine Journal (1 in 5 using CBD for pain w

90% moderate to significant reduction

• chronic management

• neuropathic pain

• affects perception of pain

• mitigates inflammatory process

• affects voltage-gated sodium channels

Opioid WithdrawalCannabis treats symptoms of Opioid withdrawal • Nausea, vomiting, diarrhea, cramping

• Muscle spasm

• Anxiety, agitation, restlessness

• Insomnia

• Runny nose, sweating

J.L. Scavone, R.C. Sterling, and E.J. Van Bockstaele. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neuroscience. 2013 Sep 17; 248: 637–654.

Cannabinoids and Addiction Treatment

Cannabinoids may impact cravings for or negative effects from:

– Nicotine

– Opiates/heroin

– Methamphetamines

– Alcohol

Mental Health• Anxiety (CBD or very low doses of THC)

• Stress

• PTSD

• Insomnia

• Depression

• Alcoholism

• Opiate withdrawal

• Phobias

Brain Health• Neurogenesis and brain plasticity

• Alzheimers

• Parkinsons

• Migraines

• Seizures

• Serotonin, Dopamine Neuroprotective

NeuroprotectionCBD may also play a role in the treatment of

• Stroke

• Psychosis

• Multiple sclerosis

• Bi-polar disorder

Cancer• Alternative to opiates for cancer pain

• THC increases appetite which can be useful in chemo or weight loss from cancer

• CBD and THC reduce nausea resulting from chemotherapy

• CBD and THC seem to sensitize patients to the cancer-killing effects of radiation or chemo

• CBD concentrates may inhibit cancer cell growth

• Whole-plant cannabinoid extracts that are dominant in CBD most promising anticarcinogenic activity

• Medical cannabis well-established as effective for symptoms related to cancer or chemotherapy

• No reliable evidence for using alone as sole treatment for cancer

Other Therapeutic Considerations• Cannabinoid synergism: Cannabinoids, Flavonoids, Terpenes +

• Whole plant vs. single molecule cannabinoids

• Phytocannabinoid-terpenoid “entourage effects”

• Cannabis – as an “adaptogen”

• Tolerance and auto-regulation • Organic

• Grown in the Earth, Under the Sun

• Non-GMO

• Cultivated and prepared properly to ensure bioavailability

TESTING• Potency, spectrum of Cannabinoids • Terpene Profiling • Flavonoid Profiling

• Pesticide Screening • Residual Solvents • Heavy Metal Testing • Mycotoxins Analysis

DELIVERY METHODSMETHOD ONSET DURATION

Inhaled 1-3 min 1 - 3 hrs

NanoTech 1- 5 min 4 - 6 hrs

Tinctures 30 - 60 min 1 - 3 hrs

Ingested/Edible 30 - 90 min 6 - 8 hrs

Topical 30 - 60 min 2 - 3 hrs

Transdermal 15 - 30 min 8 - 12 hrs

Where to Start• CBD is non-psychoactive with numerous potential health benefits • CBD is available OTC • No need to go to a dispensary unless contains THC • At a dispensary, you can find ratio’s (CBD: THC 0:1, 1:1, 4:1, 8:1, 30:1) • If using THC, start with lowest dose needed to relieve symptoms and

beware of side effects • NanoTech is most useful, then Tinctures

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