THC Flashcards
What are the effects of THC?
analgesic (perception of pain)
Euphoriant or sedative (makes you happy or tires you)
Anxiolytic/anxiogenic (change anxiety-levels)
Appetite stimulant
Hallucinogen
What are clinical uses of THC?
treatment of glaucoma
treatment of anorexia
reduce nausea
What is glaucoma?
Damage to optic nerve by buildup of fluid
What is the most pharmacologically active cannabinoid in cannabis?
delta-9 THC
How lipid-soluble is THC?
Very - high depot binding
How long does it take for THC to show behavioral effects when smoked?
5 minutes
peak effects within 30 min
last ~3 hr
Where is THC eliminated?
Mostly urine
But also some in feces (because it’s so lipid-soluble)
What is the 1/2 life of THC?
20-96hr.. 50hr for some metabolites. Stored in fat, released like a time capsule
Are cannabinoid receptors ionotropic or metabotropic?
Metabotropic
Why should there be cannabinoid receptors in the brain?
There are endocannabinoids
e.g. anadamide (stress, pain, learning), 2-AG
Why should there be cannabinoid receptors in the brain?
There are endocannabinoids
e.g. anadamide (stress, pain, learning), 2-AG
How do cannabinoid receptors modulate stress?
HPA axis is chock full of them
How is pain modulated by cannabinoid receptors?
Periaquaductal grey has a lot
Hypothalamus has a lot
Why is nausea modulated by endocannabinoids?
Area postrema is chock full of cannabinoid receptors
Does THC agonize or antagonize cannabinoid receptors?
‘agonist’
Although some studies say partial agonist
Where else are cannabinoid receptors expressed a lot?
Cortex
HC
Cerebellum
Basal ganglia (globus pallidus)
What does CB1 do in regards to GABAergic neurons?
Preferentially reduce inhibitory transmitter release
Why are there pyramidal neurons in the HC?
Hippocampus is part of the cortex! (Old cortex / archicortex - 3 layers instead of 6)
What type of input is on distal dendrites?
Excitatory
What type of input is more on proximal dendrites?
Inhibitory
What releases moderate amounts of endocannabinoids?
Released when we’re learning something (e.g. stress?)
What is the effect of moderate endocannabinoids getting released under stress?
CB1 inhibition of GABA release
What effect does CB1 inhibition of GABA release have?
EPSPs are unfettered because release of GABA is inhibited
More NMDA activation = more AMPA release
Does THC inhibit or excite long-term potentiation?
Inhibits it
Why does THC inhibit LTP?
THC inhibits CB1 receptors on glutamatergic terminals, inhibiting Ca2+ influx and suppressing glutamate release
Are CB1 receptors always activating?
No, they’re like a safety valve
Only under intense stress
What do endocannabinoids do in the HC?
What does THC do in the HC?
Endocannabinoids activate CB1 on GABA terminals, inhibiting GABA and causing excitation
THC agonizes CB1 receptors on GABA terminals, but also on glutamate terminals, causing a NET EFFECT of inhibition
What are some inverse agonists for CB1?
What are some agonists for CB1?
What are some antagonists for CB1?
The point here: CB1 enjoys the full range of pharmacodynamic properties
Inverse agonist: rimonabant
Agonist: WIN 55,212-2
Antagonist: Ibipinabant
What is the functional difference between CB-1 receptors and adenosine receptors?
Very similar..
But CB-1
What does SR141716 to to high people?
Decreases effects
It’s an inverse agonist
What happens to reflexes / motor skills with THC?
Reflexes unaffected
Motor skills compromised, however, by inability to concentrate
What happens to attention/memory with THC?
Inability to pay attention
Short-term memory decreased
What happens to suggestions / associations with THC?
More open to suggestions
More open to seeing associations
What happens to escape latency in morris water maze with CB1-impaired mice?
They learn much more slowly
greater path length, longer escape latency, more returns
What are returns in regards to CB1-knockout mice in Morris water mazes?
They keep going back to the old place the platform was
Don’t learn that it’s changed location
What is the LD50 of THC?
No known LD50. No confirmed instances of brain pathology
Is THC withdrawal a thing?
Yes, although more mild than ethanol
High withdrawal discomfort score after 1-3 days, takes a few weeks for it to disappear
Where in the digestive system are there a lot of CB receptors?
GI tract - tons of them.
Partly increases hedonic value of foods high in fat
