Drugs of Abuse 1 – General/Cannabis Flashcards
Generally speaking, how do the drugs of abuse cause the feeling of euphoria?
Hijack the mesolimbic dopaminergic pathway – the central reward pathway
Describe the structure of the central reward pathway.
Dopaminergic neurones project from the ventral tegmental area to the nucleus accumbens
Dopamine release into the nucleus accumbens stimulates 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 delivers drug to alveoli where it easily crosses the alveoli + enters the pulmonary circulation
There is a shorter distance from the pulmonary circulation to the heart + then brain than from the site of IV injection to the heart + then brain
What are the different classes of the drugs of abuse?
Narcotics/painkillers e.g. opiate like drugs- heroin
Depressants e.g. alcohol
Stimulant e.g. cocaine, caffeine
Miscellaneous e.g. Ecstasy (mixed properties)
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 (> 60 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?
Increase in amount of 9-THC in the cigarette meaning that there is less cannabidiol
Suggests cannabis production is heading towards being more pro-psychotic
What percentage of smoked cannabis will reach the blood stream?
~ 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, cannabis levels in the brain fall rapidly too
Describe the accumulation of cannabis in fat following administration.
Cannabis is very lipid soluble so slowly accumulates in the fat
Thus, will leak from the store in fat for a long time after administration
How long will the effects of cannabis last after smoking a joint?
~ 30 days (because of storage in adipocytes)
What is an important metabolite of cannabis?
11-hydroxy THC (more potent than Delta-9-THC)
What happens to 11-hydroxy THC once it has been produced?
Excreted in bile into GI tract but then undergoes enterohepatic cycling + re-enters 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?
GPCR: negatively coupled with adenylate cyclase
By reducing cAMP, the cell doesn’t function so well (depresses cell activity)
Name one endogenous cannabinoid.
Anandamide
Describe how cannabis causes euphoria.
Cannabis binds CB1 receptors on GABA neurones + inhibits GABA neurones
Thus, remove inhibitory influence of GABA neurones on 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
Hypoactivity in ACC in chronic cannabis users
What is the Anterior Cingulate Cortex responsible for?
Performance monitoring + behavioural adjustment in order to avoid losses
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
