The Cannabinoids Flashcards
Define cannabinoid.
All substances capable of activating cannabinoid receptors
What are the 3 main pharma coactive constituents?
THC
CBD
CBN
What are the 3 classes of cannabinoids?
Endocannabinoids
Phytocannabinoids
Synthetic
What are the 3 endocannabinoid receptors?
CB1
CB2
GPR55
Where is CB1 found?
Mostly neuronal
Where is CB2 found?
Immune cells
new research suggests neuronal function
What are two types of endogenous ligands?
Anandamide and 2-AG
What are the 3 enzymes needed for synthesis?
Phospholipase D and C and diacylglycerol lipase (DAGL)
What is the precursor for endocannabinoids?
Arachidonic acid
What is the uptake mechanism for endocannabinoids?
Anandamide transporter (?)
What enzymes breakdown endocannabinoids?
Fatty acid amid hydrolase (FAAH) and monoacylglycerol (MGL)
What triggers production of the endocannabinoids 2AG or AEA?
Calcium influx or calcium mobilization in post synaptic cell
What receptor does AEA and 2AG act on?
CB1 receptors on presynaptic terminal
What happens after AEA and 2AG bind to CB1?
Depress neurotransmitter release thus altering neuronal activity
How are endocannabinoids degraded?
Taken up via Cannabinoid transporter and degraded by FAAH
What is an agonist at Cb1 and CB2 receptors?
WIN 55,212-2
What is an antagonist at CB1?
Rimonabant
What does CB1 activate?
Increases activation of inwardly rectifying K+ channels
Decreases activity of N and P/Q calcium channels which decreases neurotransmitter release
What are 5 features of endocannabinoids?
- Synthesised on demand
- Not stored in vesicles
- Not released from presynaptic terminals
- Not specific
- Tonic release of endocannabinoids
How do endocannabinoids act backwards?
Released from postsynaptic cells and act on presynaptic terminals
Where are endocannabinoids metabolized from?
Phospholipid cell membrane - highly lipid soluble
What is Sativex?
Cannabinoid medicine for treatment of spasticity due to multiple sclerosis
What are 4 distinct effects produced by cannabimimetic drugs in animals?
Rigid immobility
Decreased motor activity
Analgesia
Hypothermia
What do endocannabinoids mediate?
GABA release
Depolarization-induced Suppression of Inhibition
How does GABA inhibition occur?
Ca2+ influx into principal pyramidal cell initiates synthesis and release of endocannabinoid that activates Cb1 receptors
What is TRPV1 involved in?
pain transduction
How are cannabinoids kept out of the brain?
CB2 agonists target novel receptors and manipulate the endocannabinoid system
