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Hemp as a plant: Research Perspective
Dr. Eric Downer Assistant Professor in Human Health & Disease,
Director BSc Human Health & Disease, Dept. Physiology, Trinity College Dublin,
IRELAND
Topics of talk
*What are cannabinoids?
*What are the effects of cannabinoids on the body?
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Topics of talk
*What are cannabinoids?
*What are the effects of cannabinoids on the body?
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Topics of talk
*What are cannabinoids?
*What are the effects of cannabinoids on the body?
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Topics of talk
*What are cannabinoids?
*What are the effects of cannabinoids on the body?
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Cannabinoids Plant-derived (phyto) cannabinoids
Tetrahydrocannabinol (THC)
Cannabinol (CBN)
Cannabidiol (CBD)
Cannabichromene (CBC)
Endocannabinoids
R(+)WIN 55,212-2
CP 55940
JWH 133
Anandamide
2-AG
Synthetic cannabinoids Terpenoids
Limonene
Myrcene
Pinene
Linalool
Biosynthesis of cannabinoids/terpenoids
5-Carbon isoprenoids
isopententyl diphosphate (IPP)
dimethylallyl diphosphate (DMAPP)
Adapted from Booth & Bohlmann,
2019
olivetolic acid
farnesyl diphosphate (FPP)
geranyl diphosphate (GPP)
geranyldiphosphate:olivetolate geranyltransferase
Cannabigerolic acid (CBGA)
monoterpene synthases (mono-TPS)
monoterpenes
sesquiterpene synthases (sesqui-TPS)
sesquiterpenes
Tetrahydrocannabinolic acid (THCA)
cannabidiolic acid (CBDA)
cannabichromenic acid (CBCA)
CBC CBD THC CBN
Cannabinoids
*Cannabis contains a family of ~ 100-120 related compounds termed “cannabinoids”
psychoactivity No psychoactivty
Tetrahydrocannabinol Canabidiol Cannabinol
Role of endogenous cannabinoids
* Precise physiological role unknown
* Inhibit neurotransmission
* Regulation of cell signalling
* Role in CNS development
Topics of talk
*What are cannabinoids
*What are the effects of cannabinoids on the body
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Topics of talk
*What are cannabinoids
*What are the effects of cannabinoids on the body
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Cannabinoid receptors - CB1 and CB2
7 transmembrane domains
CB1 – CB2 homology -68% sequence homology in transmembrane -44% throughout entire protein
extracellular
intracellular
N H 2
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a) Ion channel changes
What happens after receptor activation
b) Neurotransmission
c) Signal transduction cascades
Topics of talk
*What are cannabinoids
*What are the effects of cannabinoids on the body
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Bonini et al., 2018
Emperor Chen Nung Diodorus Siculus
Carl Linnaeus
William O’Shaughnessy
Medical use of C. sativa
Sativex
THC and canabidiol combination Treat spasticity and neuropathic pain associated with MS
Therapeutic options
Epidiolex Therapeutic options
Cannabidiol solution Treat early-onset, treatment-resistant epilepsy syndromes
Chandra et al., 2017
Topics of talk
*What are cannabinoids
*What are the effects of cannabinoids on the body
*Therapeutic potential of cannabinoids
*What is cannabinoid research indicating
Cannabinoids and inflammation
Contro
l 10 0 0.1 1 10
0
2000
4000
6000
8000
CBD (µM)
IL1α + TNFα
**
+
IL-6
( ρg/
mL)
Data from Prof. Maeve Caldwell lab
Take home message
*Large array of cannabinoids in the plant
*Cannabinoids have diverse effects on the body
*Therapeutic angles for cannabinoids exist
*Downer lab – peripheral and central analysis
Take home message
*Large array of cannabinoids in the plant
*Cannabinoids have diverse effects on the body
*Therapeutic angles for cannabinoids exist
*Downer lab – peripheral and central analysis
Take home message
*Large array of cannabinoids in the plant
*Cannabinoids have diverse effects on the body
*Therapeutic angles for cannabinoids exist
*Downer lab – peripheral and central analysis
Take home message
*Large array of cannabinoids in the plant
*Cannabinoids have diverse effects on the body
*Therapeutic angles for cannabinoids exist
*Downer lab – peripheral and central analysis
Research group Current: John-Mark Fitzpatrick Sarah Duggan Dr. Sonia Pereira Dr. Johana Velasquez Industry collaborators GW Research Ltd Clinical collaborators Dr. Orla Hardiman (TCD/Beaumont) Dr. Lisa Costelloe (Beaumont) Dr. Orna O’Toole (MUH) Dr. Brian Sweeney (CUH) Dr. Aisling Ryan (CUH) Dr. Owen Cronin (CUH) Dr. Joe McKenna (CUDSH) Dr. Christine McCreary (CUDSH) Contact edowner@tcd.ie @downerlab
Funding
Acknowledgements
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