Lecture 17: Cannabis Flashcards
What is Cannabis?
A genus of flowering plant that contains many bioactive compounds
What are the most studied bioactive compounds from Cannabis?
THC and CBD
What are Cannabinoids?
A class of chemical compounds that act at the cannabinoid receptors
What are some common non-cannabinoid chemicals?
Terpenoids
What gives cannabis plants their characteristic smell?
Terpenoids
What effects can terpenoids have?
Terpenoids can be anti-inflammatory, anti-bacterial, and anti anxiety
What is absorption or bioavailability?
The fraction of an administered drug that reaches effectors
What is the bioavailability of smoked THC?
25%
What is the bioavailability of ingested THC?
6%
Why is THC rapidly taken up by tissues with high blood flow?
Because it is very lipophilic
Which tissues accumulate THC more slowly and release it over a longer period of time?
Tissues with less blood flow
Where does THC metabolism occur?
In the liver
Which liver enzyme works on THC?
Cytochrome P450 2C9
What kind of receptors ar Cannabinoid receptors?
Inhibitory G-protein coupled receptors
What are the two types of Cannabinoid receptors?
CB1 and CB2
What does activation of CB receptors do?
Because they are inhibitory G protein coupled receptors they decrease cAMP and inhibits the influx of calcium and decreases synaptic transmission and neurotransmitter release
What kind of agonist is THC and the CB1 receptors?
A partial agonists
What is a partial agonist at CB1 receptors?
THC
What is the mechanism of action of CBD?
The mechanism of action of CBD is poorly understood but it is though that is is a negative allosteric modulator at CB1
How does CBD affect THC?
It can blunt the psychotropic effects of THC
What are the most abundant GPCRs in the body?
CB1 receptors
Where are CB1 receptors found?
- Brain
- Peripheral organs
- Peripheral nerves
Where are CB2 receptors mostly found?
On immune cells, glial cells
What are the acute adverse effects of THC?
- Panic attacks
- Severe anxiety
- psychosis
- paranoia
- hyperemesis
How can cannabis affect a fetus?
Cannabis use may lead to neuroanatomical and behavior changes in offspring
How is Cannabis and Schizophrenia related?
Cannabis use can be linked to the development of psychosis. And can worsen psychosis
What is Psychological Dependance?
Compulsive drug seeking behavior in which the individual uses the drug repetitively for personal satisfaction, often in the face of known risks to health
What is COMT?
An enzymes that is important in breaking down the monoamine neurotransmitters
What do people with the valine copies in the gene have?
A much higher risk of developing schizophrenia if they use cannabis during adolescence
What is Physiological dependance revealed?
When withdrawal of the drug produces symptoms and signs that are frequently opposite of those sought by the user
What is Cannabis Withdrawal?
It is mild and short lived. With symptoms of restlessness, irritability, mild agitation, insomnia, nausea and cramping
What is addiction?
The inability to control the use of legal or illegal substances despite negative consequences
What are synthetic cannabinoids?
A manufactured compound whose properties imitate those of the active constituents of cannabis
Why are synthetic cannabinoids developed?
Because it’s easier to determine the dose when there is only one compound present and their are decreased off target effects
What are the some of the types of Synthetic Cannabinoids?
Nabilone
Dronabinol
Nabiximols
Rimonabant
What receptors do synthetic Nabilone and Dronabinol target?
CB1 receptors
What kind of agonists are Nabilone and Dronabinol?
Partial agonists at the CB1 receptor
How is Nabilone and Dronabinol taken?
Orally
What are Nabiximols?
A synthetic cannabinoid that has a 1:1 mixture of THC and CBD
What is Nabiximol used for?
It is used for relief of pain in adult patients suffering from MS or cancer
What is Dronabinol used for?
Nausea and vomiting in patients who undergo chemotherapy and anorexia in AIDS
What does Rimonabant do at the receptor?
It is an inverse agonist at the CB1 receptor
What was Rimonabant used for?
It was approved for obesity but later withdrawn for serious adverse effects by suppressing appetite
What are Endogenous Cannabinoids?
The molecules that the body makes themselves to bind to cannabinoid receptors
What are the two types of Endogenous Cannabinoids?
Anandamide (AEA) and 2-arachidonoylglycerol (2-AG)
What are Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) made from?
The phospholipid bilayer of the membrane
How is Anandamide made from the Phospholipid Bilayer?
N-acetyltransferase converts it into NAPE and Phospholipase D converts Anandamide
How is 2-AG made from the Phospholipid Bilayer?
Phospholipase C converts it to DAG and DAG lipase converts it into 2-AG
What kind of neurotransmitters are AEA and 2-AG?
They are retrograde neurotransmitters
How are AEA and 2-AG synthesized
Neurotransmitters that are not stored in vesicles but are synthesized on demand when needed
Why are AEA and 2-AG retrograde neurotransmitters?
Because they act on the cannabinoid receptors on the presynaptic membrane and inhibit the neuron because they target Gi
How do endocannabinoids affect other neurotransmitters?
They decrease neuronal release of other transmitters
What is synthesis of 2AG and AEA stimulated by?
An increase concentration of intracellular calcium when the postsynaptic neuron becomes depolarized by the action of a neurotransmitters
What are AEA and 2AG cleared from the synapse and inactivated by?
Fatty-acid amide hydrolase (FAAH) or monoacylglycerol (MAGL)
What effects do FAAH/MAGL inhibitors have?
They are analgesic but do not produce typical psychoactive effects of THC, sedation, catalepsy or hypothermia
