Cannabis Flashcards
What is Cannabis
A genus of flowering plant
What are the primary bioactive compounds studied in Cannabis
Tetrahydrocannabinol (THC)
Cannabidiol (CBD)
Define Cannabinoids
Class of chemical compounds that act act the cannabinoid receptor (Includes THC and CBD)
Define phytocannabinoids
Cannabinoids originating from the natural cannabis plant
What gives cannabis its plant smell
terpenoids
What non-cannabinoid compound is in cannabis, what do they do
Terpenoid and hundreds more, they do not bind to the cannabinoid receptor
Terpenoids have anti-inflammatory, anti-bacterial, and anti-anxiety effects
No clinical trial to support this
Why is Cannabis hard to understand
Cannabis contains hundreds of different chemicals, hard to know all of the chemical interactions
Different strains vary in the compounds they contain and thus, it becomes hard to standerdize
Define absorption, how does it relate to Cannabis
Bioavailability of a drug
Fraction of the administered drug that reaches effectors
Mostly involved in pharmacokinetic info of THC
What is the bioavailability of THC when smoked
How quick to reach peak plasma concentration
25%
6-10 minutes
Pretty good absorption and quick
Liver is not involved
What is the bioavailability of THC when ingested
How quick to reach peak plasma concentration
6%
2-6 hours
Has to pass through digestive tract
Metabolized into metabolites
What is the distribution of THC
Highly lipophilic (Hangs out in fat)
Tissues with high blood flow rapidly take up THC
THC effect in tissues with low blood flow
Accumulate THC slowly and release it over a longer period of time (Adipose tissue (fat))
THC and fat relationship
THC is stored in fat in chronic/frequent cannabis smokers, can be released into the blood for days
Can THC cross the BBB
Yes
What enzyme helps with THC metabolism, where does this occur
Occurs in liver by cytochrome p450 2C9
What are the metabolites created from THC metabolism
Active: 11-OH-THC
Inactive: THC-COOH
THC Dose Elimination
Length: ____
Amount: ____
Composition: ____
Length: 5 days
Amount 80%-90% of THC dose
Composition: Primary in metabolites, 65% feces, 25% urine
How long can low dose THC be detected in urine
2-5 days
How long can chronic daily cannabis smokers THC dose be detected for. Why?
Can detect THC for weeks
THC is lipophilic and can accumulate in adipose tissue
Released slowly
Excretion takes place over a month
What kind of receptors are Cannabinoid Receptors. What kinds of Cannabinoid Receptors are there
Inhibitory G-protein coupled receptors (Gi coupled)
CB1 and CB2
What is the overall effect of Cannabinoid Receptors
Decrease synaptic transmission
Inhibit neurotransmitter release
What is the mechanism of Cannabinoid Receptors
decrease cAMP
Inhibits influx of Ca2+ in the firing neuron
Inhibits neurotransmitter release
What kind of agonist is THC. What receptor?
Partial agonist at CB1
What kind of agonist is CBD. How does it work? What receptor?
Negative allosteric modulator at CB1
Binds outside of the binding pocket to block receptor activation by reducing effects of THC
Not very understood
Potential Use and Issues of CBD
Could blunt psychotropic effects of THC
Hard to study because of placebo
Low bioavailability
Poorly absorbed
Where are CB1 receptors found? How abundant are they?
Among the most abundant of GPCRs
Found in the brain, peripheral organs (Heart, liver, fat, stomach, testes), and peripheral nerves
Where are CB2 receptors found? How abundant are they?
Limited distribution. Distributed mostly on immune cells
Only found in the brain on glial cells
What are the general effects of Cannabis (THC) (6)
Issues?
Euphoria
Relaxation
Disinhibition
Changes in perception
Vasodilation
Increase pulse rate
Doses to achieve therapeutic effects is many folds higher than what is biologically possible in vivo. Such high doses could lead to off target effects
Potential therapeutic effects of Cannabis (THC)
Reduction of nausea
Increased appetite
Decreased intraocular pressure (Eye pressure)
Chronic pain relief
Unwanted effects of Cannabis (THC)
Memory impairment
Dysphoric state (Unhappiness, Anger)
Visual hallucinations
Depersonalization
Psychotic episodes
Adverse Acute effects of high doses of THC
Panic attacks, severe anxiety, psychosis, paranoia, convulsions, hyperemesis (severe nausea)
Adverse Prenatal effects of cannabis use
May cause neuroanatomical and behavioural changes in offspring
Fetal growth affected (specifically neurodevelopment)
No dose-response relationship identified
What kind of cancer can cannabis use cause
Smoked cannabis can cause lung cancer
How has the legalization of Cannabis impacted motor vehicle accident
Probably only a mild effect
Despite impairing perception, cognitive functions, and reaction time there has been no drastic increase in accidents
Cases of overdosing with Cannabis? Why?
No documented evidence of death from purely cannabis
Probably because lack of CB1 receptors in the brain stem region that control respiratory and cardiovascular systems
What is the relationship between schizophrenics and cannabis use (Correlative)
Mostly correlative data that cannabis use predicts development of schizophrenia.
Lots of bias, confounding variables (unknown factor that increases risk of cannabis use and psychosis), and reverse causality (people already with psychosis are more likely to use cannabis)
What is the relationship between psychosis and cannabis use (Conclusion)
In most people cannabis does not lead to the development of schizophrenia
- Cannabis can be a trigger in the development of schizophrenia in at-risk populations (those with the genetic predisposition)
- Cannabis can worsen pre-existing schizophrenia
- Cannabis can elicit acute psychosis
Psychological dependence
Behavioural
Continued compulsive use of a drug for personal satisfaction despite knowing its risks
Physiological dependence
Physical
Withdrawal of drug causes symptoms and signs that are opposite of what the user wants
Weight changes
Flu like symptoms
Depression
Effects of Cannabis withdrawal
Relatively mild and effects are short-lived
Restlessness, Irritability, Mild agitation, Insomnia, Nausea, and Cramping
May be worse in chronic, long term users
What is the definition of Addiction (Substance use disorder)
Inability to control the use of legal/illegal substances despite their negative consequences
How id Addiction diagonesed
11 Diagnostic criteria
2/11 mild
4/11 moderate
6+/11 severe
What percentage of cannabis users develop a substance use disorder
9%
What are synthetic cannabinoids
Manufactured compounds whos properties are meant to imitate the active constitutions of cannabis
Why do we use synthetic cannabinoids
Increased specificity
Decreased off target effects
Easier dosing
Better controlled studies (Clinical studies fail less often)
What is Nabiline, how is it administered
Synthetic analog of THC (Oral)
Partial agonist
What is Dronabinol, how is it administered
Trans-isomer of THC (Oral)
Partial agonist
What does Dronabinol treat
Nausea and vomiting during chemotherapy
Anorexia in AIDS wasting syndrome
What is Nabiximol
Cannabis extract, a botanical drug
What does Nabiximol contain and what does it treat
1:1 mixture of THC and CBD
Multiple sclerosis or Cancer
What has more psychotropic effects
Smoked Cannabis or Sublingual Spray
Smoked Cannabis
What has less psychotropic effects
Smoked Cannabis or Oral THC Analogs
Oral THC Analogs
What is Rimonabant
Inverse agonist at CB1 receptor
What was Rimonabant used for
Used to treat obesity
Had serious side effects (depression and suicide ideation)
Why do Humans evolve to have Cannabinoid receptors
Not because of Cannabis
Endocannabinoids
Endogenous cannabinoids that mediate mood, feeding, and
motor function
What are the two types of endocannabinoids
Anandamide (AEA)
2-arachinoyl glycerol (2-AG)
How are endocannabinoids made
Formed from the phospholipid bilayer of the cell membrane
What are AEA and 2-AG and what are there functions
Retrograde neurotransmitters used in endocannabinoid signaling
Synthesized on demand, and works as a break to shut off neuron
What are the overall effects of endocannabinoid
Similar to THC
Decreases neuronal release of other transmitters. Acts as a break in active neurons
Where are endocannabinoids produced? Why?
Produced in active regions of the brain
Synthesis of 2AG and AEA is initiated by an increase of intracellular Ca2+ which occurs when postsynaptic neuron is depolarized by a neurotransmitter
How are endocannabinoids deactivated? What happens if these enzymes are not around?
Fatty-acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) clear endocannabinoids from the synapse and inactivate them
Suppressing these enzymes will prolong the activity of endocannabinoids
What are the effects
and side effects of FAAH and MAGL inhibitors
Analgesic effects, treatment of chronic pain
Sudden death
What conditions will enhance CB1 activity the most when using FAAH and MAGL inhibitors
A2G and AEA are released on demand at the site of action
Thus, the greater the A2G and AEA levels the greater the CB1 activation when these endocannabinoids are inhabited
What effects do FAAH and MAGL inhibitors not have
Do not have the typical THC effects: sedation, catalepsy, hypothermia, and psychoactive effects in general
