2-cannabis and cannabinoids Flashcards
what is cannabis
genus of flowering plant, contains many bioactive compounds (THC and CBD)
what is the primary psychoactive compound in cannabis
THC
what are cannabinoids
class of chemical compunds that act at the cannabinoid receptors
are all cannabinoids cannabis
no
are cannabis all cannabinoids
yes i think
are THC and CBD cannabis or cannabinoids
cannabinoids that came from cannabis
what are phytocannabinoids
things that cannabis contain hundreds of
what are terpenoids
in cannabis, a non-cannadiboid constituent which gives the characteristic smell
maybe also anti-inflammatory, bacterial and anxiety
why is it difficult to harness clinical utility
because there are so many compounds with synergistic effects and many different strains
what is bioavailalability
absorption, fraction of an administered drug that reaches effectors (receptors, plasma, CNS)
what is bioavailalability
absorption, fraction of an administered drug that reaches effectors (receptors, plasma, CNS)
what is bioavailability and time to reach peak plasma concentration time for smoking weed
25%
6-10mins
what is bioavailability and time to reach peak plasma concentration time for eating weed
6%
2-6 hours
what kind of molecule is THC (philic/phobic to what)
highly lipophilic
where is THC rapidly taken up by
tissues with high blood flow
where does THC accumulate slowly
tissues with less blood flow and release it over a longer period of time
how is THC metabolized and into what
in the enzyme by CYP 2C9 into 11-OH_THC and THC-COOH
how is most of the THC excreted
as metabolites, 65% in feces and 25% in urine
how many days for 80-90% of THC to be excreted
5
how many days can you detect THC in the urine for low dose THC
2-5 days
how many days can you detect THC in the urine for chronic daily THC users
for weeks because it stores in the adipose tissues
which G protein is cannabinoid receptors
Gi
what are the types of cannabinoid receptors
CB1 and CB2
how do CB receptors work (pathway after G protein)
decrease cAMP accumulation which decreases Ca++ in firing neuron, increases K+, inhibits neurotransmitter release and synaptic transmissions
what ions are affected by cannabinoid receptor activation
inhibits influx of Ca and promotes outflux of K
what does THC do to the receptors and which receptors
THC is a partial agonist at CB1
what does CBD do to what receptor
not totally understood
but maybe negative allosteric modulator of CB1
what does CBD do to the effects of THC
it can blunt the effects of THC
where are CB1 receptors found
some of the most abundant GPCR
brain, peripheral organs (heart, liver, fat, stomach, testes) and peripheral nerves
where are CB2 receptors found
mostly on immune cells
what are the psychoactive effects of CB2 receptors
none
where are there high CB1 receptors in the brain
areas of thought, reward, memory, motor
cerebral cortex, hippocampus, cerebellum, etc
where are there low CB1 receptors in the brain
in the brain stem (autonomic reflexes)
what are the general effects of THC
euphoria, relaxation, disinhibition, changes in perceptrion, vasodilation, increase pulse rate
what are the potential theuraputic effects of THC
nausea, appetite increase, decreased ocular pressure, pain releafe
what are the unwanted effects of THC
memory impairment, dysphoric state, hallucination, depersonalization, psychosis
what can be a therapeutic potential for CBD
inflammation, anxiety, emesis, nausea, inflammatory pain, epilepsy
what are the acute effects of weed
panic attacks, anxiety, psychosis, paranoia, convulsions, hyperemesis, RARE
what are the prenatal effects of weed
maybe neuroanatomical and behavioural changes
why is weed not deadly
CB1 receptors are very sparse in the brain stem region (controls respiratory and cardiovascular)
is there a correlation with schizophrenia and cannabis
there is a lot a correlative data for schizophrenics to use more cannabis, and early cannabis use predicts later onset schizophrenia (dose dependent)
but not causation
when is cannabis use a risk for schizophrenia
when it may be a trigger for people that are genetically at risk
what is tolerance
decreased response to the effects of the drug, necessitating ever larger doses to achieve the same effect
how does tolerance work for CB1 receptors
chronic activation of CB1 receptor uncouples from intracellular downstream signal transduction events or receptor downregulation (internalization or degradation of receptor)
what is psychological dependence
compulsive drug-seeking behaviour in which the individual uses the drug receptively for personal satisfaction, often in the face of known risks to health
what is physiological depende
revealed when withdrawal of the drug produces symptoms and signs that are frequently opposite of those sought by the user
what is cannabis withdrawal like
mild, short lives
restlessness, irritability, mild agitation, insomnia, nausea, cramping
what are synthetic cannabinoids
a manufactured compounds whose properties imitate those of the active constituents of cannabis
why do synthetic cannabinoids
increased specificity
decreased off target effects
easier dosing
better controlled studies
what are the most well confirmed clinical effects
help with nausea, appetite loss
what is nabilone
synthetic analog of THC
whast is Dronabinol
a trans isomer of THC (enantiomer), approved nausea for chemo patients and weight loss for AIDs
how are nabilone and dronabinol taken?
orally
why does nabilone and dronabinol have less psychotropic effects than cannabis
b/c they are taken orally and also because the strictures are different. also because this is pure, not with the other stuff in it
what is nabiximol (sativex)
botanical drug, cannabis extract 1:1 mixture of THC and cannabinol sublingual spray pain relief for MS or cancer less psychotropic effects than smoked
what is rimonbant
how does it work
inverse agonist at the CB1 receptor
thought it would be good for obesity. it was but then people got depressed
what are the 2 types of endocannabinoids
anadamide (AEA) and 2-arachinoyl glycerol (2-AG)
what are endocannabinoids
what do they do
endogenous cannabinoids that mediate mood, feeding and motor function
how are AEA and 2-AG made
from the phospholipid bilayer of the cell membrane
what kind of neurotransmitters are AEA and 2-AG
retrograde neurotransmitters
whats a retrograde neurotransmitters
they are not stored in vesicles, but are synthesized in demand when needed
released by a postsynaptic dendrite or cell body, and travels “backwards” across a chemical synapse to bind to the axon terminal of a presynaptic neuron
how do endocannabinoids affect neuronal release
like THC, it decreases neuronal release of other transmitters
how is synthesis of 2AG or AEA stimulated
by an increase in intracellular Ca (when synaptic neuron becomes depolarized by the action of a neurotransmitter)
this is how it is only produced in activated brian regions
how are AEA and 2AG rapidly cleared from the synapse and inactivated
rapidly by FAAH
fatty-acid amide hydrolase) and MAGL (monoacylclycerol lipase
what does suppression of FAAH and MAGL cause
a prolongation of the activity of endocannabinoids (enhance CB1 activation) where AEA and 2AG levels are the highest
how were FAAH and MAGL thought to work
maybe for chronic pain
but some show severe side effects
does FAAH and MAGL produce the typical psychoactive effects of THC
no
but it does do analgesia
