Topic 4: Cannabis Flashcards
bast fibers
hollow stems of cannibus plant
aka hemp fibers
seeds
rich in oil
low in psychoactive chemicals
cannabis sativa
family Cannabacea annual weed native to Caucasus northern India Iran dioecious lots of phenotypic plasticity major source of hemp and oil
cannabinoids
main psychoactive ingredient
lipid soluble, phenolic
cannabinoids are synthesized as
carboxylic acids
smoking causes decarboxylation to neutral form
THC molecule alterations
generally result in deduced activity
BUT by changing the alkyl group of the right and ring, it is possible to produce THC-C variants with increased potency and duration of effect
THC-V is at least as potent as
LSD
CBD
cannabidiol
phytocannabinoid
40% of plant’s extract
diff structure than THC (has double bond)
Pharmacodynamics of CBD
cannabidiol has low affinity for CB1 and CB2
acts as an indirect antagonist to their agonists
potentiate THC effects by increasing CB1 receptor density
extend duration of THC effects
allosteric modulator of mu and sigma opioid
receptors
inhibit FAAH (increase endocannabinoid levels)
synthesis cannabinoids
hexanoyl coA synthase polypeptide synthase aromatic prenyltransferase THCA synthase Heat and CO2 THC!
marijuana vs. hemp enzymatic conversion of CBGA
in marijuana: THCA synthase is expressed much more than cannabidiolic acid (CBDA) synthase
in hemp the app is true
produced in
trichomes
How are cannabinoids produced in trichomes
vacuoles (which contain phenols) and plastids (containing terpenes) make their way up trichome stalk and combine inside the secretory cavity into a fibrous mat. The concentrated mat is hit by UV-B light waves
= cannabinoid creation
heavy trichome production does not mean…
higher potency
bc the resins inside the trichome may or may not contain high levels of THC
to produce euphoria how much THC o you need?
25-50ug/kilo body weight taken into the lungs
to produce a hallucinogenic effect
it is estimated that 200-250ug/kilo boy with THC taken into lungs
consumption of _ joint(s) = mild euphoric effect
1
initial effects of cannabis
mild tension anxiety
filled by pleasant feelings of wellbeing
later effects of cannabis
tranquil
rapid mood changes
moments of hilarity
contemplative silence
THC pharmacodynamics
rapidly absorbed into blood
first reaches brain then redistributed to body
THC effects on NS
- alters electrical properties of nerve membranes
- alters turnover rates of serotonin and dopamine
- effects prostaglandin synthesis
mech of action
receptors are GPCR
7 TM domains
activated by endo, phyto and synthetic cannabinoids
cannabinoids bind reversibly and stereo-selectivity
CB1
expressed in brain (CNS)
lungs, liver, kidneys
CB2
PNS
immune system, hematopoietic cells
activation of receptors
inhibit adenylate cyclase
decrease [cAMP]
inhibition of neurotransmission
cannabinoids that bind more selectively
are more desired for medical usage
where/how are endocannabinoids formed?
w/n neurons via multiple biosynthetic pathways
made “on demand” from FA precursors via PDE enzymes phospholipase C and/or D
Anandamide
endocannabinoid
aka N-arachidonoylethanolamine/AEA
via phospholipase d
name from Sanskrit word ananda = “bliss, delight”
from N-arachidonoyl phosphatidylethanolamine
degraded by FAAH, converted to ethanol amine arachidonic acid
first endocannabinoid discovered in mama brain in 1992
favours CB1
also a TRPV-1 agonist
inhibitors of FAAH
increase anandamide levels
2-arachidonoylglycerol
2-AG
endocannabinoid
agonist of CB1, CB2
ester from omega6 FA arachidonic acid and glycerol
high amount in CNS
neuromodulatory effects
activated by phospholipase C, diacylglycerol lipase
released after neuronal depol (Ca+2 influx)
endocannabinoid degradation
through reuptake by diffusion facilitated transport molecules
hydrolytic ally cleaved by enzymes like FAAH to break them down
THC metabolized by
the liver
major active metabolite of THC
11-hydroxy-9-THC
major product of THC metabolism
THC treats…
asthma, neuralgia
depression, rheumatism, epileptic seizures
glaucoma
nausea after chem
marinol
2.5-10 mg THC
synthetic
for cancer patients
oral
Nabilone
THC analogue
Eli Lily
oral medication
CBD treats
for pain mitigation
CBD and CB receptors
little affinity for CB1 or 2
indirectly stimulates endogenous cannabinoid signaling by suppressing FAAH
opposes the action of THC at CB1 = muted effects of THC
stimulates release of 2-AG
CBD at TRPV-1 receptor
binds to receptor, agonist
therapeutic effect
mediate pain perception, inflammation, body temp
“vanillin receptor” named after vanilla
vanilla and pain
vanilla contains eugenol, an essential oil that has be used to cure headaches, also helps to unclog blood vessels
at high CBD concentrations
activates 5-HT 1 A receptor directly
antidepressant effect
5HT receptor
anxiety, addiction, appetite, sleep, pain perception, nausea, vomiting
both CNS and PNS
excitatory or inhibitory response
addiction and marijuana
heavy pot smokers can be physically addicted and dependent
far less addictive than nicotine
social use does not generally lead to addiction
addiction pattern is more like alcohol
William Randolph Heasrt
1930s
campaign to ban cannabis, blamed hallucinogenic properties
wanted it banned on moral grounds
= canada and US and Europe banned it in 1937, 1938
