Cannabinoids Flashcards
cannabinoids
the 80 plus compounds that are unique to cannabis sativa
What is the most active molecule in the hemp plant?
delta9-tetrahydrocannabinol (THC)
Function of THC
protects plants from herbivores and UV light
Order of most to least resin found in plant
flowering tops > leaves > fibrous stalks
What part of the plant is used to create hemp?
the stalks
potency varies based on ____
the part of the plant used
hashish
pure resin, 10% - 15% THC
ganja/sinsemilla
tops of non-pollinated female plants, 5-10% THC
bhang
remain of plant follwing the removal of top leaves < 1% THC
Behavioral effects of THC
- inebriant
- euphoriant
- exitant (increased talking)
- hypnotic
low/moderate doses of THC
- relaxation
- increased talkativeness
- reduced coordination
- disruption in attention & cognitive function
- altered sense of time and space
high doses of THC
- hallucinatiosn & delusions
- impaired memory
- disorientation
TCH is the ___ most popular drug
3rd (behind alcohol & nicotine)
oral administration
slow absroption, highly variable, long duration of action than other routes
Why does oral administration of cannibnoids produce highly variable effects?
its difficult to regulate the dose
smoking cannibinoids
fast absorbtion
Why is smoking cannabis potentially more harmful than smoking tobacco?
- higher toxin level than tobacoo
- smoke is held in for a long time
Why is distriubtion of THC uneven?
it has high lipid solubility
Where is THC metabolized?
the liver
delta9-THC is broken down into _______
11-hydroxy-delta9-THC
How does THC and its metabolite compare?
the activity is approximatley equivalent
cannabidol
-a metbolite of THC –prolongs duration of action of delta9-THC, -blocks liver enzymes
Half-life of THC
approx 30hrs, but traces of delta9-THC and active metabolites can persist from days to weeks due to high lipid solubility
What allowed researchers to map the location of cannabinoid receptors in the brain?
radiolabeled cannabinoids
Are cannabinoid receptors metabotropic or ionotropic?
metabotropic
CB1 receptor
- located in the nervous system
- 100x more concentrated than opiate receptors
- most common metabotropic receptor
CB2 receptor
- primarily located on immune cells (T & B cells)
- low levels in CNS
CB1 receptors are highly concentrated in areas involved in:
- mood & memory
- movement
- pain processing
mood and memory
frontal cortex, hippocampus
movement
cerebellum & basal ganglia
pain processing
spinal chord, PNS, peri-aquaductal grey
CB1 receptors are in low concentrations in areas controlling:
vegetative functions
vegetative functions
brain stem
Cannabinoid receptor action
- inhibits adenylate cyclase
- close Ca2+ channels
- open K+ channels
examples of endocannabinoids
anadamide, 2-AG, PEA, noladin ether
2-AG
2-arachidonoylglycerol
PEA
palmitoylethanolamine
endocannabinoid synthesis/storage
- not stored in vesicles
- synthesized on demaned from membrane phospholipids
how is endocannabinoid signaling stopped?
enzymatic degradation
endocannabinoids are _____ messengers
retrograde
retrograde messenger
- synthesized & released by postsynpatic neuron
- acts presynaptically
retrograde signaling in endocannabinoids
close Ca2+ channels, thus decreasing GABA release and increasing pyramidal cell activity
disinhibition
inibiting an inhibitor
GABAa
ionotropic
GABAb
metabotropic
triadic configuration
input from excitatory projectionto dendritic spine, inhibitory input onto dendrite, postsynaptic side of dendritic spine inputs to excitatory projection and inhibitory projection
activation of mGlu1 on pyramidal neuron:
- results in production of endocannabinoids
- these endocannabinoids interact with the inhibitory GABA neuron
- endocannabinoid interacting with CB1 receptors on GABA neuron closes calcium channels so less GABA is released
lower 2-AG levels
GABA release is inhibited and glutamtae release is unaffected; this is the basis for long term plasticity/learning
higher 2-AG levels
GABA and glutamate release are inhibited, impaired learning
Why does THC impair memory?
its the same as having high 2-AG levels, CB1 receptors on both the GABAergic neuron and the glutamatergic neuron are activated, resulted in impaired release of GABA and glutamate
marinol
dronabinol; synthetic THC, an appetite stimulant and antiemetic (reduces vomiting)
Sativex
derived from the plant (THC & CBD),
What is Sativex used to treat?
- a mouth spray used to treat neuropathic main and spaticity in MS
- cancer pain
rimonabant
- CB1 agonist
- used to treat obesity (Europe)
- ultimatley dropped due to side effects
drug x gene interaction in THC-induced psychosis
when one is homozygous for Val/Val, cannabis use results in increased risk of developing schizophreniform disorder
