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
What effect does cannabis have on MCH and
Orexin neurones?
Cannabis inhibits the inhibitory effect of GABA on MCH neurones, thus leading to increased MCH firing
Also directly stimulates orexin production
This leads to hunger
Describe the effect of cannabis on the immune system.
Cannabis is a powerful immunosuppressant
CB2 receptor on immune cells so depresses their activity
How does cannabis cause memory loss?
Inhibits 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?
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 pathologically associated with?
Obesity
Infertility
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?
Analgesic
Treatment for symptom improvement in adult patients with moderate to severe spasticity due to MS
What can Rimonabant be used for?
Anti-obesity medication (removed from the market because it was shown to cause depression + suicidal thoughts)
What can dronabinol and nabilone be used for?
Stimulating appetite in AIDS/ Chemotherapy patients
