The Endocannabinoid System for Nurses

PresentersDr. Denise A. Foster, PhD, MSN, RN, CNE

Dr. Alexandra Christodoulou, DNP, FNP-BC, BSN, RN

June 2019

TM

ACNA Mission

To advance excellence in cannabis nursing practice through advocacy, collaboration, education, research,

and policy development.

TM

HousekeepingWelcome to our first CE Webinar!

○ All attendees are muted○ Q&A session at end - type questions in chat box

○ Moderator will read questions at end of presentation○ Process for obtaining CE Certificate of Completion

○ Evaluation survey will be emailed to you○ Complete Webinar Evaluation survey○ ACNA will send your Certificate of Completion to your email

Agenda

○ Housekeeping○ Introduction of presenters○ Endocannabinoid System (ECS)

○ Presenter: Dr. Denise A. Foster○ Therapeutic Effects of ECS

○ Presenter: Dr. Alexandra Christodoulou

Learning OutcomesAt the end of this presentation, the attendee will be able to:

1. Describe the anatomy and physiology of the endocannabinoid system.2. Classify the endocannabinoid receptors cannabinoid receptor 1 (CB1),

cannabinoid receptor 2 (CB2), and cannabinoid receptor 3 (CB3) and their locations throughout the body systems and organs.

3. Describe the endocannabinoids arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (AEA or anandamide), including synthesis and degradation.

4. Describe the function and physiology of the endocannabinoid system as it relates to two main human body systems.

5. List three therapeutic effects of the endocannabinoid system within two main human body systems.

ECS Anatomy & Physiology

Image credit: Aizpurua-Olaizola, O., Elezgarai, I., Rico-Barrio, I., Zarandona, I., Etxebarria, N., & Usobiaga A. (2017).Targeting the endocannabinoid system: Future therapeutic strategies. Drug Discovery Today, 22(1), 105-110.

Cannabinoid Receptors● CB1● CB2

Putative Endocannabinoid Receptors● CB3● CB4● CB5● TRPV1

ECS Anatomy & Physiology

Image credit: Aizpurua-Olaizola, O., Elezgarai, I., Rico-Barrio, I., Zarandona, I., Etxebarria, N., & Usobiaga A. (2017).Targeting the endocannabinoid system: Future therapeutic strategies. Drug Discovery Today, 22(1), 105-110.

Endocannabinoids● 2-AG● AEA (anandamide)

Putative Endocannabinoids● NaGly● NE● Oleamides (OS, OG)● Virodhamine● NADA● OEA

Endocannabinoid Receptor - CB1

Image credit: Zou, S., & Kumar, U. (2018). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. International Journal of Molecular Sciences, 19(833), 1-23.

○ G-protein coupled receptors

○ External stimuli Intracellular signals

○ 2-AG = Full agonist

○ AEA = Partial agonist

○ Neurotransmitter inhibition via Ca2+ channel inhibition, activation of K+ channels

Endocannabinoid Receptor - CB1 System Physiological Response

CNS Neuronal development & synaptic plasticityReduced pain transmissionRegulation of learning & memory

Immune Reduction of localized neuroinflammation and degeneration

CV Initial tachycardia, hypotension, remodeling of cardiac tissue

GI Motility, gastric acid & fluid secretion, appetite stimulation

Metabolic Regulation of lipid metabolism & glucose regulation

Skeletal Regulation of bone mass

Endocannabinoid Receptor - CB2

○ 2-AG = Full agonist○ AEA = Partial agonist, low affinity○ Peripheral immune cells○ Microglia, brainstem, skin, spleen○ Inhibit inflammatory mediators○ Reduce pain○ Mediate stress response○ Bone loss○ Neuroprotective

Image credit: Pacher, P., & Mechoulam, R. (2011). Is lipid signaling.through cannabinoid 2 receptors part of a protective system? Progress in Lipid Research, 50, 193-211,

Endocannabinoid Receptors GPR18, GPR55, GPR119

Image credit :https://mcanz.org.nz/the-endocannabinoid-system/

○ GPR18 ○ NaGl, AEA○ Migration of immune cells, BP, apoptosis

○ GPR55○ Virodhamine, AEA, 2-AG○ Inhibit inflammatory mediators○ Regulate vascular tone○ Lipid metabolism & glucose regulation○ Bone mass, neuroprotective

○ GPR119○ Pancreas & GI tract○ Lipid metabolism & glucose regulation○ Obesity & diabetes

Endocannabinoid Receptors TRPV1

Image credit: Zador, F., & Wollemann, M. (2015). Receptome: Interactions between three pain-related receptors or the “triumvirate” of cannabinoid, opioid and TRPV1 receptors. Pharmacological Research, 102, 254-263.

○ Sensory neurons, brain○ Senses for tissue damage

○ Molecular target for CBD anti-hyperalgesia○ Paradoxical analgesic effects

via desensitization○ Anti-nociception○ AEA = full agonist

Known Endocannabinoids - 2-AG

Image credit: Wikimedia Commons

○ Immunomodulator○ Anti-nociception○ Anti-cancer○ Blood cell growth○ Microglia ‘clean-up crew’○ Food intake & energy metabolism○ Anxiety, depression, addiction

2-AG

Known Endocannabinoids - AEA

Image credit: Wikimedia Commons

AEA○ Anti-nociception○ Anti-inflammatory○ Anti-cancer○ Hypotension, vasodilation○ Anabolic regulator○ Body temperature○ Apoptosis○ Infectious response

Putative Endocannabinoids

○ N-arachidonoyl glycine (NaGly) - brain anti-inflammation, cancer○ 2-arachidonoyl glyceryl ether (noladin ether [NE]) -

anti-inflammatory, chronic nociception○ Oleoyl serine (OS) - bone, osteoblasts, osteoclast apoptosis○ Oleoyl glycine (OG) - adipogenesis, insulin sensitivity, hyperphagia○ O-arachidonoyl ethanolamine (virodhamine) - cardioprotective,

anti-inflammatory○ N-arachidonoyl dopamine (NADA) - pain, renal & cardiovascular

function, COX-2 production, prostaglandins○ Oleoylethanolamine (OEA) - food intake, weight loss

Retrograde Signaling

Image credit: Zou, S., & Kumar, U. (2018). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. International Journal of Molecular Sciences, 19(833), 1-23.

○ Act backwards

○ Postsynapse Presynapse

○ Increased intracellular Ca2+ or GPCRs

○ Inhibit release of neurotransmitters

○ Decrease excitatory or inhibitory effects of neurotransmitters

Endocannabinoid Synthesis & Degradation

NAPE AEADAG 2-AG

Glycerol

2-AG FLAT MAGL AA

2-AGAEA EthanolamineImage credit: Manira, A. E., & Kyriakatos, A. (2010). The role of

endocannabinoid signaling in motor control. Physiology, 25(4), 230-238.

FAAH

Therapeutic Effects of the ECS:Homeostasis and Metabolism

○ Maintaining homeostasis and regulation of human body systems

○ Metabolic syndrome and overactivation of the ECS

○ Alteration of gut microflora○ GPR55 deficiency in relation to endocrine

function and energy metabolism

Therapeutic Effects of the ECS:Central and Peripheral Nervous System

○ Cognitive processes, emotions, fear/anxiety○ Memory and learning ○ Alzheimer’s Disease○ Mental Illness○ Neuroprotection○ Pain○ Anti-Inflammatory effects of CNS

Therapeutic Effects of the ECS:Immune System

○ Gatekeeper of the immune system○ Autoimmune Diseases○ ‘Subduing’ the immune system (anti-inflammatory)○ Allergies○ Antitumor/Anticancer properties

Therapeutic Effects of the ECS: Cardiovascular System

○ Vasodilation○ Myocardial contractility○ Cardioprotection○ Reducing blood pressure

Therapeutic Effects of the ECS:Respiratory System

○ AEA and pro-inflammatory effects on airway epithelial cell permeability

○ CBD anti-inflammatory and lung remodeling in allergic asthma

○ THC and antitussive, anti-inflammatory activity○ CB2 activation and restriction of subsequent

allergic inflammation

Therapeutic Effects of the ECS: Gastrointestinal System

○ Motility, smooth muscle contractility, anti-propulsive effects, and visceral sensitivity

○ Intestinal inflammation ○ Mucosal barrier permeability○ Apoptosis and colon cancer ○ Hepatic lipogenesis on nonalcoholic fatty liver

disease○ Implications for mucosal healing in IBD

Therapeutic Effects of the ECS: Musculoskeletal System

○ CB1 antagonists and mitochondrial function○ Potential role in bone formation ○ CBD reduces bone loss○ CB1 receptors in DMD

Therapeutic Effects of the ECS: Integumentary System

○ Keratinocyte, melanocyte, and sebocyte homeostasis

○ Pain○ Anti-inflammatory effects - pruritis, atopic

dermatitis, and acne○ Regulate growth of skin appendages○ Treat and prevent dermal fibrosis in Systemic

Sclerosis

Thank you for attending!

Questions?Please type your question into the chat box!

Our moderator will read questions as time permits.

TM

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