Drugs of Abuse 1 – General/Cannabis Flashcards
Generally speaking, how do the drugs of abuse cause the feeling of euphoria?
The hijack the mesolimbic dopaminergic pathway – the central reward pathway
Describe the structure of the central reward pathway.
The dopaminergic neurones project from the ventral tegmental area to the nucleus accumbens
Dopamine release into the nucleus accumbens will stimulate the feeling of euphoria
Put the routes of administration of drugs in order of speed of absorption.
Smoking > IV > Snorting > Oral
Why is smoking slightly quicker than IV injections?
Smoking brings the drug to the alveoli where it easily crosses the alveoli and enters the pulmonary circulation
There is a shorter distance from the pulmonary circulation to the heart and then to the brain than from the site of IV injection to the heart and then to the brain
What are the different classes of the drugs of abuse?
Narcotics/painkillers – e.g. opiate like drugs
Depressants – e.g. alcohol
Stimulant – e.g. cocaine, caffeine
Miscellaneous
What is an alkaloid?
Any class of nitrogenous organic compound of plant origin that has profound physiological actions on humans
What are the active components of the Cannabis sativa plant?
Cannabinoids (there are over 60 of them in the plant)
What is the most potent cannabinoid in the plant?
Delta-9-tetrahydrocannabinol (Delta-9-THC)
What is another important cannabinoid that appears to counteract some of the negative effects of the potent cannabinoid?
Cannabidiol
How has cannabis production changed over the last 10-15 years?
There has been an increase in the amount of 9-THC in the cigarette meaning that there is less cannabidiol
This suggests that cannabis production is heading towards being morepro-psychotic
What percentage of smoked cannabis will reach the blood stream?
Around 30%
Describe the accumulation of cannabis in the brain following administration.
Cannabis levels in the brain rise very quickly after administration but, because the brain is highly perfused, the cannabis levels in the brainfall rapidly as well
Describe the accumulation of cannabis in fat following administration.
Cannabis is very lipid soluble so it slowly accumulates in the fat
This means that cannabis will leak from the store in the fat for a long time after administration
How long will the effects of cannabis last after smoking a joint?
Around 30 days (because of the storage in adipocytes)
What is an important metabolite of cannabis?
11-hydroxy THC (this is more potent than Delta-9-THC)
What happens to this metabolite once it has been produced?
It is excreted in the bile into the GI tract but then it undergoes enterohepatic cycling and re-enters the blood stream where it can exert its physiological effects
Because of this, plasma Delta-9-THC levels are a poor measure of intoxication
Where are the different cannabinoid receptors found?
CB1 – brain
CB2 – peripheral immune cells
What type of receptor is the cannabinoid receptor?
G protein coupled receptor – negatively coupled with adenylate cyclase
Name one endogenous cannabinoid.
Anandamide
Describe how cannabis causes euphoria.
Cannabis binds to CB1 receptors on GABA neurones and inhibits the GABA neurones
This means that they remove the inhibitory influence of GABA neurones on the dopaminergic neurones of the rewards pathway, hence there is increased firing of the dopaminergic neurones –> euphoria
What area of the brain does cannabis interact with that is linked to its psychotic effects?
Anterior Cingulate Cortex
There is hypoactivity in the anterior cingulate cortex in chronic cannabis users
What is this part of the brain responsible for?
Performance monitoring and behavioural adjustment
Which part of the brain does cannabis act on to stimulate food intake?
Lateral hypothalamus
What are the two main groups of neurones that are involved in stimulating appetite?
MCH (melanin concentrating hormone) neurones
Orexin neurones
What effect does cannabis have on these neurones?
Cannabis inhibits the inhibitory effect of GABA on MCH neurones, thus leading to increased MCH firing
Cannabis also directly stimulates orexin production
This leads to hunger
Describe the effect of cannabis on the immune system.
Cannabis is a powerful immunosuppressant
How does cannabis cause memory loss?
It inhibits the production of BDNF (brain derived neurotrophic factor), which is important in the hippocampus in forming memories
In general, cannabis has a depressant effect on the hippocampus
How does cannabis cause impaired psychomotor performance?
It depresses the cerebral cortex
How does cannabis cause cardiovascular effects?
Cannabis acts via the TRPV1 receptor to cause calcium influx
What are the cardiovascular effects of cannabis?
Activating the TRPV1 receptor leads to calcium influx –> tachycardia
In which part of the body does cannabis cause a lot of vasodilation?
Conjunctivae (bloodshot eyes)
Why is it not possible to overdose on cannabis?
There is very low expression of CB1 in the medulla (which is where you find the cardio-respiratory centres)
What is the upregulation of cannabinoid receptors in the adipocytes associated with?
Obesity
State 4 drugs that are either cannabinoid agonists or antagonists.
Dronabinol - Delta-9-THC
Nabilone - Delta-9-THC
Sativex - Delta-9-THC + cannabidiol
Rimonabant – CB1 antagonist
What can cannabinoid receptor agonists be used for?
Treatment of nausea due to chemotherapy
What is Sativex used for?
Treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis
What can Rimonabant be used for?
Anti-obesity medication (it was removed from the market because it was shown to cause depression and suicidal thoughts)
