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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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