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Pharmacology & Therapeutic Potential of Cannabinoids
Presentation · October 2019
DOI: 10.13140/RG.2.2.26641.58725
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Anglia Ruskin University
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Pharmacology & Therapeutic 
Potential of Cannabinoids
Ishan Panagoda
BSc (Ang Rus), MSc (Ang Rus)
Background
Cannabinoids
Cannabinoid Receptors
Therapeutic potential 
Topics
Background
Background
u Humans have been using Cannabis for thousands of years for many purposes, such as medicine, 
fiber and fuel. 
u Evidence suggest its use as early as 2600 B.C.E in China in treating pain and dysmenorrhea. 
u Cannabis is a genus of flowering plants that belongs to the family Cannabaceae. 
u Three main species of cannabis are recognised: Cannabis sativa, Cannabis indica, and Cannabis 
ruseralis. However, all three may be treated as Cannabis sativa (C. sativa)
u First named C. sativa by Leonhart Fuchs in 1542, and it was introduced to British medical 
practice in 19th century as an analgesic, anti-spasmodic, anti-emetic and hypnotic. 
u However, decline of the medicinal cannabis began early in the 20th century
u Decline was hastened by increasing concerns about recreational use. 
u Recent advances in cannabinoid pharmacology alongside the discovery of endocannabinoid 
system (ECS) have re-ignited the interest in cannabis-based medicine. 
u Policy is rapidly changing, and cannabis can now be prescribed for medicinal use in many 
countries, including the UK.
Cannabinoids
Cannabinoids
Cannabinoids are basically derived from three sources: 
A. Phytocannabinoids are cannabinoid compounds produced by cannabis plants.
Cannabis plants contain at least 400 naturally occurring chemical entities and of which more 
than 60 of them are phytocannabinoid compounds
E.g. The principal phytocannabinoids are delta 9-tetrahydrocannabinol (δ-9THC) and 
cannabidiol (CBD).
In contrast to psychotropic THC, non-psychotropic phytocannabinoids, such as CBD, 
cannabigerol (CBG), do not activate potently cannabinoid CB1 and CB2 receptors.
B. Endocannabinoids are neurotransmitters produced in the brain or in peripheral tissues, and act 
on cannabinoid receptors. E.g. 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide
(anandamide) are the best-studied endogenous cannabinoids.
C. Synthetic cannabinoids, synthesized in the laboratory, are structurally analogous to 
phytocannabinoids or endocannabinoids and act by similar biological mechanisms.
Phytocannabinoids
u Phytocannabinoids are lipid-soluble compounds that are synthesised in the disk cells and stored 
in the secretory cavity in glandular trichomes in female C. sativa plants
u Extraction and isolation is followed by high-performance liquid chromatography (HPLC), gas 
chromatography, melting point, infrared spectroscopy analysis for purity. 
Figure 1|Single-photon fluorescence and scanning 
electron microscopy (SEM) images of a glandular 
trichome (a) and of secretory cavity (b) of C. sativa 
var. Bedrobinol with 561 nm excitation. Anatomy of 
glandular trichomes captured with SEM (Ebersbach, et 
al., 2018) 
Figure 2| Glandular Trichome (Booth and Bohlmann, 
2019) Phytocannabinoids accumulate in the secretory 
cavity of the glandular trichomes. Terpenes are 
responsible for the odor and flavor of the different 
Cannabis strains.
Phytocannabinoids (Cont.)
Figure 3|Phytocannabinoids CBD and Δ9-THC (Maroon and Bost, 2018)
(a) Δ9-THC and (b) cannabidiol (CBD) are biosynthesized as 
tetrahydrocannabonolic acid (THC-A) and cannabidolic acid (CBD-A) from a 
common precursor cannabigerolic acid (CBG). 
These phytocannabinoids in their natural acidic form are considered ‘inactive’
When cannabis grows, it produces THC-A and CBD-A, not Δ9-THC and CBD. When 
cannabis is heated, such as through smoking, cooking, or vaporization, THC-A and 
CBD-A are decarboxylated into Δ9-THC and CBD (i.e. “active” forms)
All classes of phytocannabinoid compounds found in marijuana and hemp, 
including Δ9-THC and CBD, are derived from various changes to base molecular 
structure of cannabigerol-type compounds
Cannabinoid Targets on 
CNS Actions
THC
CB1R
Partial
agonist
CB2R
Partial
agonist
CBD
CB1R Antagonist
CB2R Antagonist
Table 1|Comparison of THC and CBD features
Cannabinoid 
Receptors
A
Cannabinoid Receptors
u Two types: cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R)
u CB1 and CB2 are cell membrane receptors that belong to the G-protein coupled receptor (GPCR)
family.
Figure 4| Topology of a Class A GPCR (Morales, Hurst and Reggio, 2017) Figure (A) An extracellular (EC) N 
terminus; (2) seven transmembrane alpha helices (TMHs) arranged to form a closed bundle; (3) loops connecting 
TMHs that extend intra- and extracellularly; and, (4) an intracellular (IC) C terminus that begins with a short helical 
segment (Helix 8)oriented parallel to the membrane surface. Ligands for Class A GPCRs are generally thought to 
enter the receptor via the extracellular space. Figure (B) illustrates an extracellular view of the receptor structure. 
Here you see the opening that allows the ligand, beta-funaltrexamine to descend into the receptor binding pocket 
A B
Cannabinoid Receptors (cont.)
u CB1 and CB2 cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the 
enzymes that synthesize and degrade endocannabinoids are collectively known as the 
endocannabinoid system (ECS)
Figure 5| CB2 Cannabinoid Receptors as a Therapeutic Target
(Dhopeshwarkar and Mackie, 2014)
Activation of CB2 
receptors by natural 
or synthetic ligands 
favors a range of 
receptor 
conformations that 
can variably affect 
different signaling 
pathways 
Therapeutic 
Potential 
Nonpsychoactive Cannabinoids: Role against 
Oxidative Stress, Inflammation, and Cancer
Figure 6| General representation of the 
signaling pathways involved in CBD anti-
inflammatory effects (Pellati, et al., 2018). 
Cannabinoids reduce peripheral inflammation by 
acting at TRPV1, CB2, and GPR55 receptors; these 
interactions lead to downregulation of enzymes 
involved in the production of prostaglandins, 
reactive oxygen species, and cytokines. MAPK 
inhibition and NF-kB downregulation, together 
with PPARγ-mediated reduction of lipid 
peroxidation, are also involved in the anti-
inflammatory effects of cannabinoids in the CNS.
Novel therapeutic use of CBD in Treatment 
Resistant Epilepsy (TRE)
u Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are forms of epilepsy, which are rare 
and particularly difficult to treat. 
u Epidiolex, 99% pure, oil-based CBD extract has proven to be an attractive treatment option.
u Treatment with Epidiolex is associated with a meaningful reduction in seizure frequency in a high 
proportion of patients with severe TRE.
u Open label study in children with TRE showed that after 12 weeks of treatment, overall seizure 
frequency was reduced by 54% in all patients, and by 63% in DS patients. 
Figure 7| Median % Reduction in Total Seizures
References
Booth, J.K. and Bohlmann, J., 2019. Terpenes in Cannabis sativa–From plant genome to humans. Plant
Science.
Dhopeshwarkar, A. and Mackie, K., 2014. CB2 Cannabinoid receptors as a therapeutic target-what does
the future hold? Molecular pharmacology, 86 (4), pp.430-437. 10.1124/mol.114.094649 [doi].
Ebersbach, P., Stehle, F., Kayser, O. and Freier, E., 2018. Chemical fingerprinting of single glandular
trichomes of Cannabis sativa by Coherent anti-Stokes Raman scattering (CARS) microscopy. BMC plant
biology, 18 (1), pp 275.
Elliott, W. and Chan, J., 2018. Cannabidiol Oral Solution (Epidiolex). Internal Medicine Alert, 40 (16).
Maroon, J. and Bost, J., 2018. Review of the neurological benefits of phytocannabinoids. Surgical
neurology international, 9, pp.91. 10.4103/sni.sni_45_18 [doi].
Morales, P., Hurst, D.P. and Reggio, P.H., 2017. Molecular targets of the phytocannabinoids: a complex
picture2017. Phytocannabinoids. Springer. , pp.103-131.
Pellati, F., Borgonetti, V., Brighenti, V., Biagi, M., Benvenuti, S. and Corsi, L., 2018. Cannabis sativa L.
and nonpsychoactive cannabinoids: their chemistry and role against oxidative stress, inflammation, and
cancer. BioMed research international, 2018.
Sekar, K. and Pack, A., 2019. Epidiolex as adjunct therapy for treatment of refractory epilepsy: a
comprehensive review with a focus on adverse effects. F1000Research, 8.
Thank You! Any 
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