Cannabis II Flashcards
How do we become tolerant to THC?
with chronic exposure, CB1 receptors become internalized (removed from the neuronal membrane) –> which results in low response to same amount of THC and own endocannabinoid which could result in saddness/depressed moods
what are some of the withdrawal symptoms of THC?
hot flashes (and problems regulating temperature)
sweating
runny nose
loose stools
irritability
anxiety
insomnia
usually not severe because of long half-life of drug and metabolites so it results in very gradual decrease
What is the link between THC and cannabis?
cannabis does not contain overtly toxic materials, but pyrolysis (decomposition due to high temperatures) generates mutagenic polycyclic hydrocarbons, phenols and resold
users exhibit more precancerous lesions and airway inflammation than non-users
largest study shows no correlation between smoking and lung, pharynx, larynx and mouth cancers
using a water-pipe (bong) in which smoke first passes through a water layer may remove cancer-causing components, but also tends to remove THC from the smoke and increase the Tar: THC ratio
What are some of the risk factors for THC causing schizophrenia
heavy users shown to have increased risk of schizo
estimated to be related to 8% of all reported schizophrenia cases
increases risk 2 times the average in longitudinal studies over 15 years (6X the average in subset of heavy users)
linked with high [thc]/ low cannabidiol varieties
increased risk the earlier first exposure occurs (earlier you start smoking weed)
link to mutations in COMT gene which metabolizes dopamine (controversial) and AT, a protein that controls gene transcription and cell death in neurons
weed varieties like ‘skunk’ are not good because of its high THC to low cannabidiol concentrations
What are 5 arguments for causing schizophrenia?
- cannabis precedes schizo by 1-5 years
- cannabis use typically worsen symptoms and progression of disease
- there is a dose-response relationship (greater the dose, the higher the risk)
- positive (e.g. hallucinations) and negative (apathy) aspects of schizophrenia are mimicked experimentally by THC intoxication
- cannabis use is linked to depression, a motivational syndrome, which ares similar to the negative aspects of schizophrenia
what is the link between intelligence and cannabis use?
use of cannabis prior to age 18, is linked to drop of 8 IQ points by age 30
what is synethetic/herbal marijuana? and example
Spice, or K2
it is chemicals found in herbal products that tend to be the cast-offs of various research programs that were trying to find new drugs to characterize CB1 and CB2 receptors
contents are unknown and they are made in labs to mimic effects of marijuana … not clinically tested in animals
What was the trend of popular synthetic marijuana from 2010 to 2014.. what were the names? why is the trend always changing?
in 2010 –> JWH018 was the major synthetic cannabinoid and was legal because the government had no idea about it
in 2012 –> XLR11 become popular as JWH018 became illegal as governments caught on… XLR11 became quite popular till early 2014
in 2014 –> UR144 became popular later in 2014 as XLR11 became illegal in early 2014
these change all the time because governments keep catching onto them late and then new ones are already being made
what makes synthetics so much stronger and more potent?
By changing the ‘X” tail backbone of THC molecule to halogens like fluorine then you get a tighter binding of drugs to CB1 receptors and by changing the “R” subgroup of the THC molecule you can get even more potent effect
what is the hCB1 EC50 ratio number mean?
this reflects the concentration of drug you need to reach half the max effect at the receptor
smaller the number the more potent the drug is and the less of it you need to get high
if you add fluorine to the ‘X’ group, then you get a lower HCB1EC50
What does the term “spiceophrenia” come from?
comes from the effects of spice mimicking schizophrenia because of its high potency to CB1 receptors
can cause seizures, hallucinations, agitation, nausea, vomitting,
and overall opposite effect of organic and non synthetic compounds like cannabis
also the initial BP (blood pressure) for these people is very high, same with pulse and respiration
What are some of the effects of synethic cannabinoids being full agonists at endocannabinoid receptors?
THC is a partial agonist but synthetics are full agnosits and more POTENT agnostic at CB2 receptors than THC (CB2 receptors are more common outside of CNS) therefore, they produce larger effects on the CV system and more pronounced psychological effects
may stimulate intracellular signalling pathways that THC does not normally stimulate since its only a partial agonist
may promote rapid desensitization and internalization of receptors because its a full agonist
What is the purpose of vaporizers? how is it compared to smoking?
the delivery of marijuana when smoked can have negative effects for medicinal use
vaporizers are good because they reduce the carcinogen byproducts that are formed during combustion
vaporizers heat cannabis without burning it
the THC vaporizes at around 180-200 degrees Celsius without combusting the plant material
vaporizers can deliver equivalent amounts of THC compared to smoking
by looking at THC concentration in plasma, theres little difference between how much THC gets in your blood when smoked vs. vaporized
What is the evidence (experiment) that shows that vaporizers produce fewer combustion products compared to smoking?
The higher the temp of vaporizer, the more THC it yields but also yields other products like by-products
When THC is vaporized at the highest temperature (230 degrees C with a Volcano) it produces a THC concentration that is higher than what is produced with the cigarette smoking AND it has fewer byproducts formed than cigarettes which shows that vaporizers might be a better alternative to medicinal marijuana
also yields much less carbon monoxide
what is munchies and what are three mechanisms of why it occurs?
- increased olfaction
- increased pleasure when eating food high
- increased activity of hunger signaling pathways
In what ways are the CB1 receptors linked to heightened olfaction?
cannabinoids control food intake by affecting olfaction (smell)
this is via CB1 receptors on glutamate releasing neurons that normally stimulate inhibitory neurons in the main olfactory bulb
normally, hunger circuits stimulate these receptors via endocannabinoids to trigger feeding
THC mimics this response and does it when your not supposed to be hungry which leads to think you’re hungry
What is the olfactory pathway for when you are not hungry?
- glutamate is released from glutamergic neurons
- this stimulates release of GABA from GABAergic neurons
- this has an inhibitory effect on mitral cells and their ability to transmit olfactory information to other brain regions
what is the olfactory pathway for when you are in presence of cannabinoid (or just very hungry)?
- glutamate release is prevented due to CB1 activation on glutamate-releasing nerve endings
- this results in GABAergic cells not to be stimulated and release little gABA
- this removes the inhibitory effect on mitral cells and they are able to transmit olfactory information to other parts of the brain
Describe the experiment done to show that THC increases sensation of pleasure/reward from food?
Control rats were given no sucrose (vehicle)
experimental rats where either given 20% sucrose with no THC beforehand or 20% sucrose with THC beforehand
usually 20% sucrose is not enough to cause a hedonistic (pleasurable response in rats)
the rats who were primed with THC before 20% sucrose administration, felt heightened dopamine increase towards the sucrose and increase pleasure and more of a hedonistic response than rats who were not given THC
What are the effects of cannabinoids on endogenous appetite signaling pathways like Grhelin?
Grehelin is a peptide synthesized in the gut that is a hunger signal, and acts in the hypothalamus
it can stimulate appetite and eventually increase body weight
this is partially due to its effects on AMP (AMP-activated protein kinase) regarded as an energy sensor in cells
Cannabinoids have similar effects on APK as gremlin does… it tells you that you are hungry
it is proposed that the grhelin receptor and cannabinoid receptor pair up as part of a hunger signal pathway
what is the Cannabinoid and ghrelin pathway?
Normally CB1 and GHS-R1A (grhelin receptor) need to be activated both simultaneously to activate AMPK (activated in hypothalamus to trigger hunger) and increase feeding and hunger signals
the receptors may physically link together and form a dimer instead of being two separate monomers and then increase a bigger AMPK response in the hypothalamus and a larger hunger response
In what ways can cannabinoids be used as treatment for nausea/vomitting
the primary signal for N/V seems to be 5-HT
Delta-9 THC prevents 5HT release and also binds to 5HT3 receptors and decreases their activity
cannabidiol is an agonist at 5HT1A auto receptors and prevents 5HT release
what is Cannabinoid hyperemesis syndrome?
in long term frequent users
constant vomitting and stomach pains
compulsive hot showers to releave these symptoms
all symptoms of this vanish when stopping cannabis use
cause is unknown but body temp controlled in hypothalamus where there are many CB1 receptors
What do the stats of cannabis use and motor vehicle accidents show?
seems to have most severe effects on automated tasks in driving like staying in lane compared to concentration intensive tasks like reversing and distance keeping
from meta analysis –> acute cannabis risk nearly doubles risk of severe injury and death
other studies show that effects of alcohol and cannabis are additive and if taken separately they might have a small dose to not cause any harm but when taken together can have additive dose and have a more dangerous impairment
