17 Cannabis Flashcards
What is cannabis?
Genus of flowering plant;
- contains many bioactive compounds but most studied are tetrahydrocannabinol (THC) and cannabidiol (CBD)
- THC is primary psychoactive compound
What are cannabinoids?
Class of chemical compounds that act at the cannabinoid receptors
What constituent of cannabis gives it its characteristic smell?
Terpenoids
In vitro and in vivo studies have found that some terpenoids have _________, _________ and _________ effects, but no clinical trials have been conducted to support this
In vitro and in vivo studies have found that some terpenoids have anti-inflammatory, antibacterial and anti-anxiety effects, but no clinical trials have been conducted to support this
Why is it difficult to create a clinically appropriate form of cannabis?
Cannabis contains hundreds of phytocannabinoids at varying concentrations between different plants and the effect of cannabis is possibly due to surround effect, or synergy between the compounds
Pharmacokinetics of THC:
ADME
- Bioavailability of smoked THC vs ingested
- Time to peak plasma concentration?
Absorption (bioavailability):
- smoking provides rapid and efficient delivery from lungs to the brain
- bioavailability of smoked THC is 25%, reaching peak plasma concentration in 6-10 minutes
- Ingested:
- bioavailability ~6% (because of 1st pass metabolism)
- Time to peak plasma concentration is 2-6 hours
Pharmacokinetics of THC:
ADME
How is THC distributed?
- THC is highly lipophilic so rapidly taken up by tissues with high blood flow (heart, lungs, brain, liver)
- Tissues with less blood flow accumulate THC more slowly and release it over a longer period of time (eg adipose tissue)
- THC stored in fat in chronic, frequent smokers can be released into the blood for days
THC metabolism occurs mostly in the ______ by the enzyme __________
THC metabolism occurs mostly in the liver by the enzyme cytochrome P450 2C9 producing the metabolites:
- 11-OH-THC
- THC-COOH
THC metabolism occurs mostly in the liver by the enzyme cytochrome P450 2C9 producing what 2 metabolites?
THC metabolism occurs mostly in the liver by the enzyme cytochrome P450 2C9 producing the metabolites:
- 11-OH-THC
- THC-COOH
How long does it take for THC to be excreted and in what form?
Within 5 days 80-90% of a THC dose is excreted, primarily as metabolites
- 65% in feces
- 25% in urine
Can detect THC in urine 2-5days for low dose, and longer (weeks) for chronic users (because it accumulates in fat tissue)
What kind of receptors are cannabinoid receptors?
What are the 2 “flavours”?
Inhibitory G-protein coupled receptors (Gi coupled)
- CB1
- CB2
What effect does an agonist binding to a CB receptor have?
CB receptors leads to decrease in cAMP (cyclic adenosine monophosphate) accumulation which inhibits the influx of Ca2+ in the firing neuron and inhibits NT release
(↓cAMP → ↓Ca2+ → ↓NT release
What effect do CB receptors have on synaptic transmission and NT release?
decrease synaptic transmission
inhibit NT release
THC is a _________ at CB1
(partial agonist, full agonist, antagonist)
THC is a partial agonist at CB1
(partial agonist, full agonist, antagonist)
Cannabidiol (CBD) is poorly understood but some evidence suggests that it acts as a ______ at CB1
Cannabidiol (CBD) is poorly understood but some evidence suggests that it acts as a Negative Allosteric Modulator at CB1 (binds outside the binding pocket to block receptor activation)
How do CBD and THC compete at the CB1 receptor?
CBD can blunt psychotropic effects of THC
Which of the two CB receptors are more abundant in the brain?
- CB1 receptors are among the most abundant GPCRs
- Found in brain, peripheral organs (heart, liver, fat, stomach testes) and peripheral nerves (ie found almost everywhere)
- CB2 mostly on immune cells
- glial cells in the brain
What does preclinical research suggest about CBD therapeutic potential?
CBD has potential for management of inflammation, anxiety, emesis, nausea, inflammatory pain, and epilepsy
- may influence effects of THC
- No clinical data for these claims
What are 6 general effects of THC?
- euphoria
- relaxation
- disinhibition
- changes in perception
- vasodilation
- increase pulse
What are four potential therapeutic effects of THC?
- attenuation of nausea
- increased appetite
- decreased intraocular pressure
- chronic pain relief
What are five unwanted effects of THC?
- memory impairment
- dysphoric state
- visual hallucinations
- depersonalization
- psychotic episodes
What are four adverse effects of cannabis use?
- Acute effects (rare and usually associated with high doses of THC)
- Panic attacks
- severe anxiety
- psychosis
- paranoia
- convulsions
- hyperemesis
- Prenatal effects
- may lead to neuroanatomical and behavioural changes in offspring
- fetal growth, particularly neurodevelopment, but dose-response relationship not identified
- Lung cancer : particularly through smoked cannabis
- Driving:
- increase risk of MVA
- Impairs perception, psychomotor performance, cognitive functions and affective functions
- Decreased rxn time
What is the probable reason why there have been no documented evidence of death exclusively linked to cannabis overdose?
Because of sparsity of CB1 receptors in the brain stem region that controls respiratory and cardiovascular systems
How is cannabis linked to schizophrenia?
Strictly through correlation
- correlative data suggests schizophrenics are more likely to use cannabis and early cannabis use dose-dependently predicts the development of schizophrenia later on
- these studies do not indicate causation
- Majority of cannabis users do not develop schizophrenia
- however, cannabis can elicit acute psychosis and can worsen course of pre-existing schizophrenia
- may be trigger in the development of schizophrenia in at-risk populations (ie those with genetic predisposition)
- however, cannabis can elicit acute psychosis and can worsen course of pre-existing schizophrenia
