Exam 3: Cannabinoids Flashcards
1
Q
for the cannabinoid system was the receptor iscovered first or the endogenous ligand for the receptor
A
receptor first in 1988 - recent
2
Q
psychoactive cannabinoids exert their effects by interacting with the ____
A
endocannabinoid neurotransmitter system
3
Q
what are the 2 natural endocannabinoids
A
anandamide
2-AG (2-arachidonylglycerol)
4
Q
on-demand synthesis and release of cannabinoids requires
A
increased calcium ions in postsynaptic neuron!!!
5
Q
endocannabinoids are generated from
A
inositol phospholipids in the membrane that have fatty acid arachidonic acid
6
Q
what converts NAPE into anandamide
A
phospholipase D
7
Q
what is the precursor to 2-AG
A
DAG
8
Q
2-AG and anandamide are taken up by
A
endocannabinoid membrane transporters on glial cells
9
Q
COX-2
A
breaks down both 2-AG and anandamide
10
Q
FAAH
A
breaks down anandamide into arachidonic acid and ethanolamine
11
Q
MAGL
A
breaks down 2-AG into arachidonic acid and glycerol
12
Q
2 cannabinoid receptors
A
CB1 and CB2
13
Q
general description of cannabinoid receptors
A
inhibitory
metabotropic
- inhibit cAMP formation, voltage sensitive Ca channels, and they open K channels
presynaptic heteroreceptors - retrograde signaling
14
Q
CB1 receptors
A
located on axon terminals
presynaptic - typically on glutamate or GABA neurons
concentrated in brain and spinal cord!!
15
Q
CB2 receptors
A
most abundant outside CNS (for in CNS it is hippocampus and cerebellum)
immune system, bone, fat, GI tract
expressed by microglia
16
Q
what is a partial agonist at CB1 receptors ONLY
A
anandamide
17
Q
what is a full agonist at CB1 and CB2 receptors
A
2-AG
18
Q
3 endocannabinoid signaling mechanisms discovered
A
- retrograde signaling
- anandamide remains in postsynaptic cell and activates a canabinoid receptor or TRPV1 receptor
- endocannabinoids activate receptors on nearby astrocytes, resulting in release of glutamate
19
Q
endocannabinoid always synthesized in…
A
POSTSYNAPTIC element!!!
inc in intracellular Ca in postsynaptic triggers it
20
Q
endocannabinoid retrograde signaling
A
CB1 receptors are activated by 2-AG and inhibit Ca mediated neurotransmitter release
CB1 receptors found on synapses with MGlu5 receptors in hippocampus and cerebellum
21
Q
negative feedback mechanism for regulating glutamate
A
- glutamate activates MGlu5 receptor
- this inc intracellular Ca and triggers 2-AG synthesis and release
- 2-AG diffuses across synapse and activates presynaptic CB1 receptors
- inhibits voltage gates Ca channels and reduces glutamate release
22
Q
TRPV 1 receptors in brain
A
regulate pain processing, mood, motor function, learning and memory
- spicy foods
23
Q
cannabis
A
marijuana and hemp produced from the cannabis plant
24
Q
2 most abundant cannabinoids
A
THC and CBD
25
what is marijuana potency dependent on
THC content
| it varies deending on growing conditions and the genetic strain of the plant
26
cannabis indica
female plant, 3-7 ft tall, less than 5% THC - growing towards 10%
stringer/smellier "skunk weed"
27
cannabis sativa
most common
grows up to 18ft tall
produces 1-5lb of buds/smokable leaves
low level of THC (less than 3%)
28
what differs between cannabis indica and sativa
indica is more potent has more THC
| both have same pharmacodynamics
29
sinsemilla
without seeds
no pollination
highest level of THC (5-11%) very potent THC
30
resin (hashish) thc content
15-20%
31
hash oil THC content
exceeds 60%!! - moe potent than smoking a bud from the actual plant
32
what has happened to the potency of thc cannabis overtime
it has dramatically increased
33
what class is marijuana
schedule 1 drug
- recretional use legal in 18 states
medical use lgeal in 37 states
BUT federally it has no accepted medical use
34
ROA for marijuana
inhalation: smoking (joints, pipes, bongs)
- typical joint has 0.5-0.8g cannabis with 8% THC
- vaporization: inhalation, ingesting water vapor
oral: edibles - pills, brownies, gummies
topical: oils/creams marketed for local activity, high CBD, low THC
Dabbing: cannabis extracted with butane to form waxy residue with high THC
35
absorption of marijuana
smoking:
- THC easily absorbed by lungs
- 20-70% original THC in joint reaches lungs (only 30% enters circulation)
oral administration: GI tract, delayed onset of action, dec bioavailability
- first pass metabolism - low and variable blood concentrations
- 50% THC metabolized to 11-OH-THC before entering circulation
36
distribution of marijuana
high lipid solubility - cannabinoids persist in body for long time - weeks to months if chronic user (crosses BBB and placental)
THC carried by blood and deposited in organs
Depot binding!!! - accumulates in fat stores over long period of time it is released into circulation - can detect on drug test for a while
smoked/vaped: rapid onset of action
oral: delayed onset but lasts longer
37
metabolism of marijuana
oral: first pass metabolism
| - 50% THC metabolized to 11-OH-THC
38
excretion of marijuana
55% excreted as feces!!!
20% in urine
blood THC levels decline quick but complete elimination is much slower due to fat tissue
39
psychoactive annabinoids exert their effects by interaction with the ____
endocannabinoid neurotransmitter system
40
where are CB1 and CB2 receptors found?
CB1: cns, lungs, liver, kidneys
- presynaptic heteroreceptors regulate releas of other neurotransmitters
CB2: immune system, GI tract
41
mechanisms of reinforcement
- activation of mesolimbic DA system
| - cannabinoids INDIRECTLY stimulate firing of DA neurons in VTA an enhance DA release in nucleus accumbens
42
are CB1 receptors expressed by DA neurons?
NO
- cannabinoids activate CB1 receptors in GABAergic neurons of VTA reducing local GABA release
which releases DA neurons from inhibitory effects of GABA increasing cell firing
43
THC effect on user: amygdala
panic/paranoia
44
THC effect on user: basal ganglia
slower reaction time
45
THC effect on user: brain stem
antinausea effects (medulla) and suppressed pain
46
THC effect on user: cerebellum
impaired coordination
47
THC effect on user: hippocampus
impaired memory, forgetful
48
THC effect on user: neocortex
altered thinking, judgement, sensation, PFC changes
49
THC effect on user: nucleus accumbens
euphoria - indirectly activate DA
50
THC effect on user: spinal cord
altered pain sensitivity
51
THC: learning and memory
cannabinoids suppress induction of long term potentiation (needed for learning) in the hippocampus by inhibiting glutamate neurons
long term potentiation aka learning requires glutamate!!
- spect imaging shows reduced blood flow to hippocampus
52
THC: pain
CB receptors in the PAG in brainstem on cells that process pain signals - lots of CB1 in PAG, lots of CB2 in spinal cord
activating CB1 will shut down the PAG and block pain signals from getting to brain
CB1 and CB2 receptors regulate both pain perception and the cognitive-affective responses to pain
53
what receptors does CBD oil target vs THC
CBD oil targets CB2R
| THC targets both CB1 and CB2
54
effects of cannabinoid use depend on
dose
frequency of use
characteristics of user - male or female
setting
55
what is the "high" associated with
euphoria, exhiliration, sense of disinhibition
56
relaxation is the most common reported effect of being___
stoned
| sensroy rxns: floating sensations, enhances visual and auditory perception, visual illusions, slowing of time
57
how much to smoke and eat to get mild euphoria
2mg smoked
| 5mg eaten
58
how much to smoke or eat to get perceptual and time distortions
7mg smoked
| 17mg eaten
59
how much to smoke or eat to get hallucinations, delusions, disortions of body image
15mg smokes
| 25mg eaten
60
is there a lethal dose?
NO
LD50 ~ 1:40,000
nearly 1,500 lbs of marijuana in about 15 min to kill onself - you wuld die of smkoe inhalation first
61
acute effects
inc flushing of skin, blood flow o skin, inc HR, vasodilator (blood shot eyes), pupils dilate
inc hunger
reduced motor activity/drowsiness
62
what brain regions involved in THC effects on hunger/feeding behavior
VTA and Nucleus Accumbens: enhanced pleasure from eating (why does this taste so good)
Limbic system: enhanced palatability (getting creative in kitchen)
Stomach and SI: regulates ghrelin, appetite stimulating hormone
Hypothalamus: inc craving/food intake
63
effects of cannabinoids on psychomotor performance
acute exposure produces deficits in driving ability
- slow rxn time, poor coordination, drowsiness
bigger effects when marijuana combined with alcohol or other drugs
64
smoking marijuana can sometimes produce transient psychotic symptoms
agitation, paranoia
- expectation also plays role in what effects the drug will produce
65
acute effects cannabinoid
```
impaired verbal learning and memory
impaired working memory
impaired attention
impaired inhibitory control and other executive functions
impaired psychomotor function
```
66
chronic effects cannabinoids
impaired verbal learning and memory
impaired attention; attentional bias
possibly impaired psychomotor function
possibly impaired executive function
67
recovery of function with abstinence
likely persistent effects on attention and psychomotor function
possibly persistent effects on verbal learning and memory
68
amotivational syndrome
chronic cannabis use associated with aimlessness, dec motivation, lack of planning, dc productivity
69
cannabis and educational performance
inverse relationship
inc cannabis dec educational performance
poor academic performance can also inc canabis use
70
tolerance
regular users report tolerance to behavioral and subjective effects
memory impairment, motor coordination, accelerated time passage
71
PET imaging shows
widespread decreases in brain CB1 receptor binding in regular marijuana smokers
- receptor binding recovered following abstinence from cannabis within a few days
72
chronic cannabis exposure could change brain
unclear if brain abnormalities occurred prior to or after marijuana use
impaired striatal dopamine function: long term disturbances in mood, motivation, cognition
73
physical health
smoking marijuana damages lungs
- smoke contains tar, carcinogens, carbon monoxide
regular marijuana smoking is associated with various respiratory symptoms
risk of heart attack significantly elevated during the hour after smoking marijuana, even ppl in 20s or 30s
74
reproductive consequences
| males and females
males: developing breast tissue due to inc release of breast-feeding hormone prolactin
- reduced sperm production and motility, erectile dysfunction
females: menstrual cycle irregularities
if used during pregnancy crosses placenta to fetus
- adverse effects may persist through adulthood
75
medical uses of cannabis: cancer
reduces nausea and vomiting associated with chemo
| limited evidence showing reduced tumor growth in patients
76
medical uses of cannabis: weight
promotes weight gain in disorders that diminish appetite
77
medical uses of cannabis: pain
reduces neuropathic pain from trauma or surgery
78
medical uses of cannabis: glaucoma
relieves intraocular eye pressure
79
medical uses of cannabis: autoimmune disease
inhibits immune system functioning
| appears effective for multiple sclerosis
