Lecture 16 - Cannabinoids Flashcards
a genus of flowering plant which contains many bioactive compounds
cannabis
what are the two major bioactive compounds that come from the cannabis plant that have been studied?
tetrahydrocannabidiol (THC) and cannabidiol (CBD)
what is the primary psychoactive compound in cannabis?
THC
a class of chemical compounds that act at the cannabinoid receptors
cannabinoids
cannabis contains hundreds of non-cannabinoid constituents, including _____ which give the plant its characteristic smell
terpenoids
in vitro and in vivo studies found some terpenoids to have:
anti-inflammatory, anti-bacterial and anti anxiety effects
have any clinical studies been conducted on terpenoids?
no
why are cannabis constituents difficult to study?
there is the possibility of synergy between compounds
the fraction of an administered drug that reaches its effectors
absorption/bioavailability
what is the most rapid and efficient method of delivering THC to the body?
smoking
the bioavailability of smoked THC is _____, reaching peak plasma concentration in _____
25%, 6-10 minutes
the bioavailability of ingested THC is _____, reaching peak plasma concentration in _____
6%, 2-6 hours
why is THC so readily taken up by the body tissues (particularly those with high blood flow)?
it is highly lipophillic
true or false: tissues with low blood flow accumulate THC more slowly and release it over a long period of time
true
in frequent cannabis smokers, THC is stored in _____ and can be released into the blood for _____
fat, days
THC metabolism occurs mostly in the liver by:
cytochrome P450 2C9 (CYP 2C9)
metabolism of THC produces:
11-OH-THC and THC-COOH
within five days, ____% of a THC dose is excreted
80-90
cannabinoid receptors are:
inhibitory GPCRs (Gi coupled)
what are the two types of cannabinoid receptors?
CB1 and CB2
CB receptors lead to decreases in ______ accumulation which inhibits _______
cAMP, the influx of calcium in the firing neuron (inhibits neurotransmitter release)
overall, activating cannabinoid receptors will:
decrease synaptic transmission and inhibit neurotransmitter release
THC is a:
partial agonist at CB1
while the CBD mechanism of action is poorly understood, there is some evidence to suggest that it can act as:
a negative allosteric modulator at CB1
true or false: CB1 receptors are among the most abundant GPCRs
true
where are CB1 receptors found?
the brain, peripheral organs (heart, liver, fat, stomach, testes), and peripheral nerves
where are CB2 receptors found?
mostly on immune cells
what are the general effects of THC?
- euphoria
- relaxation
- disinhibition
- changes in perception
- vasodilation
- increased pulse rate
what are the potential therapeutic effects of THC?
- attenuation of nausea
- increased appetite
- decreased intraocular pressure
- chronic pain relief
what are the unwanted effects of THC?
- memory impairment
- dysphoric state
- visual hallucinations
- depersonalization
- psychotic episodes
the only condition in which high quality data exists to show the therapeutic effects of CBD`
pediatric epilepsy (Dravet syndrome)
list four adverse effects of using THC
- acute effects (ex: panic attacks and psychosis)
- prenatal effects (neuroanatomical and behaviour changes)
- lung cancer
- increased risk of vehicle accidents
is there any evidence to show that cannabis use leads to death?
no
does cannabis use (particularly in adolescence) increase the risk of later developing psychotic disorders, such as schizophrenia?
overall, no. however, cannabis can elicit acute psychosis, can worsen the course of pre-existing schizophrenia, and may be a trigger in the development of schizophrenia in at-risk populations
a manufactured compound whose properties imitate those of the active constituents of cannabis
synthetic cannabinoids
why create synthetic cannabinoids?
- increased specificity
- decreased off-target effects
- easier dosing
- better controlled studies
three conditions in which clinical trials have confirmed that THC can be an effective treatment
- refractory nausea/vomiting
- anorexia appetite loss
- HIV/AIDS
a synthetic analog of THC
nabilone
trans isomer of delta9-THC, approved for nausea and vomiting treatment in patients undergoing chemotherapy and anorexia in AIDS wasting syndrome
dronabinol
both nabilone and dronabinol are:
partial agonists at the CB1 receptor
rimonabant is an:
inverse agonist at the CB1 receptor
taking rimonabant leads to a reduction in:
appetite
why was rimonabant withdrawn from market shelves?
associated with serious adverse effects (depression and suicidal ideation)
what are endocannabinoids?
endogenous cannabinoids produced by the body to act at CB receptors
what are the two types of endogenous cannabinoids?
anandamide (AEA) and 2-arachinoyl glycerol (2-AG)
anandamide (AEA) and 2-arachinoyl glycerol (2-AG) are made from:
the phospholipid bilayer of the cell membrane
what type of neurotransmitters are anandamide (AEA) and 2-arachinoyl glycerol (2-AG)?
retrograde neurotransmitters (synthesized on postsynaptic neuron and act on presynaptic neuron)
AEA and 2-AG are not stored in vesicles, but rather:
synthesized on demand when and where they are needed
like THC, endocannabinoids _____ release of other neurotransmitters
decrease
synthesis of AEA and 2-AG is stimulated by:
increases in concentration of intracellular Ca++ when the postsynaptic neuron becomes depolarized by the action of a neurotransmitter
endocannabinoids are only produced in the regions of the brain that are:
activated
AEA and 2-AG are rapidly cleared from the synapse and inactivated by:
fatty-acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL)
fatty-acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors do not produce the typical psychoactive effects of THC, but do have:
analgesic effects
