Drugs of Abuse - Cannabis Flashcards
Outline the reward pathway
- Dopaminergic neurones that originate in the ventral tegmental area and project down to the nucleus accumbens in the ventral striatum
- Dopamine secretion at the nucleus accumbens in the ventral striatum causes the euphoria
1) Mention the 4 different routes of administration of these drugs of abuse and outline the path they take
2) Which one of these is the fastest route and why?
- Nasal (snorting)
- Oral
- Inhalation (smoking)
- Intravenous (injecting)
- Inhalation has the fastest route to the brain
What are the 4 classifications of the drugs of abuse and give examples
- Depressants - alcohol, benzodiazepams, barbiturates
- Stimulants - cocaine, amphetamine, methamphetamine
- Narcotics / painkillers - opiates e.g. heroin
- Miscellaneous - cannabis, ecstasy
What are the 2 main cannabinoids found in cannabis and which one is more potent?
- Cannabidiol
- Delta9 - THC - MOST POTENT
Cannabidiol is believed to have a ….. ….. from the ….. ….. of Delta9 - THC
Cannabidiol is believed to have a protective effect from the negative effects of Delta9 - THC
Which one of these cannabinoids - cannabidiol or delta9 - THC is the harmful cannabinoid?
- Delta9-cannabidiol
Why is there low and slow absorption if you intake a drug using oral administration?
- Low absorption due to first pass metabolism by the liver
- Slow due to the time it takes for it to pass through the digestive tract and enter the circulation in order for it to reach the brain
Why don’t you get complete absorption with the inhalational (smoking) route of drug administration?
- Because not all of the smoke will reach far down enough into the lungs and lots of it is breathed out
1) Where does cannabis accumulate and why?
2) In what form does it accumulate in these tissues?
1)
- In poorly perfused tissues
- In fatty tissues - as it is very lipophilic
2)
- As fatty acid conjugates of 11-OH-THC - a metabolite of delta9-THC which is even more potent
What is the metabolite of cannabis which is even more potent than the most potent cannabinoid prior to metabolism?
- 11-OH-THC is a metabolite which is even more potent than delta9-THC which is the most potent cannabinoid
Give 2 ways that cannabis can persist in the system
- Enterohepatic cycling
- Bio-accumulation of fatty acid conjugates of 11-OH-THC in fatty tissue and poorly perfused tissue
Why do chronic cannabis users get more high than non-chronic users?
- Because of the stores of the very very potent 11-OH-THC metabolite which bio-accumulates in fatty tissue and in the poorly perfused tissues
- It even accumulates in the fatty tissue of the brain
What is the most prevalent endogenous cannabinoid?
- Endogenous anandamide
What are the 2 types of cannabinoid receptors and where are they located?
What type of receptors are these cannabinoid receptors?
1)
- CB1 receptors - in brain areas
- CB2 receptors - in peripheral immune cells
2)
- Gi-protein coupled - and negatively coupled to adenylate cyclase
Explain the mechanism for how endogenous cannabinoids or even exogenous cannabinoids can cause euphoria
- Anandamide (endogenous cannabinoid) or the exogenous cannabinoids e.g. delta9-THC can bind CB1 receptors, particularly on GABAergic neurones in the brain which have many CB1 receptors
- These CB1 receptors are negatively coupled with adenylate cyclase, thereby depressing the function of these GABAergic neurones
- Therefore less inhibition of the dopaminergic neurones which would otherwise be greatly inhibited by the GABAergic neurones
- So more active dopaminergic neurones in the reward pathway - remember this originates in the ventral tegmentum and terminates in the nucleus accumbens within the ventral striatum
