Drugs of Abuse 1: General/Cannabis Flashcards
Why are drugs abused?
They hijack the body’s natural reward pathway
How does the reward pathway work?
There is a collection of dopaminergic neurones that originate in the ventral segmental area (VTA) and they project to the nucleus accumbens- dopamine release here stimulates feelings of reward and euphoria
What causes dopamine release at the nucleus accumbens?
Anything that makes you feel good
How do drugs that are snorted reach the brain?
Drugs go into the nasal sinus where it then diffuses across a mucus membrane into the bloodstream (venous system). It then goes back to the heart then up to the brain
What is the slowest route of administration of a drug?
Oral
What is the fastest route of administration?
Smoking- little difference between smoking and injecting though
How do IV drugs reach the brain?
Drug goes into vein and then to heart and then to brain
How do smoked drugs reach the brain?
It goes into the lungs were a lipid soluble drug will pass with ease across the alveoli. Then the drug goes into the pulmonary circulation then back to the heart and then to the brain- shorter distance than IV
What are the 4 classes of drugs of abuse?
Narcotics/painkillers- opiate like drugs
Depressants (downers)- alcohol etc
Stimulants (uppers) cocaine, nicotine etc
Miscellaneous- e.g. cannabis and ecstasy
What effect do depressants have on brain activity?
Slow it down
What is an alkaloid?
Any of a class of nitrogenous organic compounds of plant origin which have pronounced physiological actions on humans- include drugs (morphine) and poisons (atropine)
Which part of the cannabis sativa plant contains active cannabinoids?
Every part
How many cannabinoids are there in a cannabis plant?
Over 60
What is the most potent cannabinoid there is?
Delta-9 tetrahydrocannabinol (delta9-THC)
What cannabinoid protects against some of the negative effects of delta9-THC?
Cannabidiol- it’s anti-psychotic
How have the concentrations of delta9-THC and cannabidiol changed in recent years? What effect has this had?
Delta9-THC increased and cannabidiol decreased
Joints are more potent
What are the major routes of administration of cannabis?
Inhalation and oral
Why is oral administration of cannabis not very effective?
It is heavily affected by hepatic first pass metabolism
When smoked, what percentage of the cannabis dose will be lost and not even reach the alveoli?
50%
What percentage of cannabis dose reaches the blood normally?
33%
Why does cannabis reach the brain quicker than fat?
The brain is very highly perfused
Why do the peak effects of cannabis on the brain last only a couple of hours?
As it is so well perfused, it will leave quickly as well
Why do cannabinoids build up in the fat slowly?
Cannabis is very lipid soluble- fatty acid conjugates build up
Why are the effects of cannabis very long lasting? (how long?
Adipose tissue is a massive store of cannabinoids which slowly leak back into bloodstream over 30 days
Which metabolite of cannabis is more potent than delta9-THC?
11-hydroxy THC
Where is 11-hydroxy-THC produced?
In the liver
How is 11-hydroxy-THC excreted?
In bile into the GI tract
What can happen to 11-hydroxy-THC in the GI tract?
It can be reabsorbed into the enterohepatic circulation
Why does the concentration of delta9-THC in the blood give a poor measure of the degree of intoxication?
11-hydroxy-THC can exert toxic effects as well as other metabolites
Cannabinoids also leak out of the fat into the blood
When are peak cannabinoid levels in the fat reached?
After around 5 days
What endogenous cannabinoid receptors are there and where are they found?
CB1- Brain
CB2- Peripheral cannabinoid receptors found on immune cells
What sort of receptor are cannabinoid receptors?
G-protein coupled that are negatively coupled with adenylate cyclase
Why is cannabis classified as a depressant?
It slows down cellular activity by depressing the action of adenylate cyclase
What is special about cannabinoid receptors in the brain?
They are the most prevalent G-protein coupled receptor in the brain
What is an example of an endogenous cannabinoid like substance?
Anandamide
What effect does GABA have on central reward pathway?
It has a negative influence on dopaminergic neurones of central reward pathway which prevents reward system from permanently firing
If your brain wants you to feel reward, what does it do?
It inhibits GABA
How does cannabis have an effect on the central reward pathway?
It binds to CB1 receptors in GABA neurones and switches off GABA function leading to euphoria
Who are more vulnerable to psychotic effects of cannabis?
Younger people
What is an important part of the brain that cannabis interacts with which is normally used in performance monitoring with behavioural adjustment?
Anterior cingulate cortex
How does cannabis interact with anterior cingulate cortex?
Causes hypoactivity in the ACC
How does cannabis stimulate food intake?
It has a positive effect on neurones in lateral hypothalamus which are involved in appetite and stimulating hunger
What neurones are involved in stimulating hunger?
Orexinergic and melanin concentrating hormones
How does cannabis have an effect on MCH neurones?
It inhibits GABA neurones which normally have an inhibitory influence on MCH neurones but this is removed by cannabis
What else does cannabis seem to directly stimulate in terms of appetite stimulation?
Orexin production which is an appetite stimulating hormone
What effect does cannabis have on the immune system?
It is a very potent immunosuppressant-
Negative effects on number of immune cells- decreases B and T cell numbers and decreases cytolytic activity of NK cells
How does cannabis cause memory loss?
It affects the limbic regions - depressive effects on hippocampus in particular will lead to amnestic effects
Decreases effects of BDNF
What is BDNF?
Brain derived neurotrophic factor- important peptide in the hippocampus that allows the formation of memories
How does cannabis affect psychomotor performance?
It causes depression of the cerebral cortex
How does cannabis have cardiovascular effects?
It activates the TRPV1 receptor which leads to calcium influx and can cause tachycardia
Why do the eyes become bloodshot?
Vasodilation occurs particularly in conjunctivae
Why can’t cannabis kill you?
CB1 receptors are very prevalent in the brain but their concentration in the medulla is very low and the medulla is responsible for controlling cardio-respiratory function so it can’t really be affected by cannabis use
What happens to CB receptors in a number of disease states?
They’re upregulated
What will upregulation of CB receptors in adipocytes lead to?
Obesity
What are CB agonists mainly used to treat?
Anti-emetics like dronabinol and nabilone
Chemotherapy patients to reduce nausea
What is dronabinol used to treat in people with AIDs?
Loss of appetite and weight loss
What is sativex used to treat?
Symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis
What is rimonabant?
CB receptor antagonist which can be used as anti-obesity medication
