Pharm 13 - Drugs of Abuse 1 - Cannabis Flashcards
Where in the brain is euphoria induced?
Nucleus accumbens (ventral striatum) - dopamine released here
General pharmacodynamics of drugs of abuse, why is there euphoria?
Ventral tegmental area = area where there are dopaminergic cell bodies
These cell bodies project onto the nucleus accumbent (ventral striatum)
Known as mesolimbic dopamine system –> central reward pathway
Rank the routes of administration from slowest to fastest
- Eat - GI tract, very slow absorption
- Snort - mucous membranes of nasal sinuses. Slow absorption
- Inject - veins, rapid absorption
- Smoke - small airways and alveoli, rapid absorption
What is the classification of drugs of abuse
- Narcotics/painkillers - opiate like drugs e.g. heroin
- Depressants - alcohol, benzodiazepines, barbiturates
- Stimulants - cocaine, amphetamines, caffeine, methamphetamine
- Miscellaneous - e.g. cannabis, ecstasy
Which is the most potent cannabinoid
Delta-9 tetrahydrocannabinoid
D9-THC
Which cannabinoid may reduce some of the negative effects of THC?
Cannabidiol
The negative symptoms of cannabis seem to be more dose related
Y
Describe the bioavailability of cannabis when orally taken and when inhaled
Orally = 5-15%. Delayed onset, slow metabolism, first pass metabolism
Inhalation = 25-35%
Cannabinoids are VERY lipid soluble substances. What does this mean
It slowly accumulates in fatty tissues (poorly perfused), and in long term smokers it can slowly leak back into the blood
What is the metabolite of D9-THC which is even more potent than D9-THC
11-hydroxy-THC
This metabolite of cannabis (metabolised in the liver) is more potent than D9-THC
11-hydroxy-THC more likely to accumulate in fat
What is the problem with enterohepatic cycling and cannabis
Cannabis is very lipid soluble, so if trying to eject cannabis out of the gut in bile, it will just keep getting reabsorbed by the SI
There is a poor correlation between plasma cannabinoid concentration and degree of intoxication.
Y
There is an endogenous cannabinoid system. What are the receptors involved and where are they?
CB1 receptor - hippocampus / cerebellum / basal ganglia / cerebral cortex
CB2 receptor - Immune cells
What type of receptors are cannabinoid receptors and how are they linked to Adenylate cyclase
G-protein coupled receptors
Negatively linked to adenylate cyclase - They are depressants
Name an endogenous cannabinoid-like substance produced
Anandamides - binds to CB receptors
How does cannabis cause euphoria
Central reward pathway (VTA and Nucleus Accumbens) is inhibited by GABA.
Cannabis binds to CB1 receptors and causes disinhibition of GABA - causes dopaminergic neurones to start firing
Which part of the brain does cannabis affect that is to do with performance monitoring and behavioural adjustment?
Anterior cingulate cortex - deals with error detection
Cannabis causes hypoactivity of this area
Why does taking cannabis stimulate hunger?
Cannabis has positive effect on neurones in the lateral hypothalamus
Inhibits GABA (which inhibits Melanin Concentrating Hormone - MCH) - stimulating appetite
Cannabis directly stimulates orexin production (hormone/neurotransmitter which stimulates appetite)
Cannabis is an immunosuppressant, how?
It has a negative effect on various immune cells.
Decreases B/T cell count, decreases cytolytic activity of NK cells, etc
What other effects can cannabis have?
- Memory loss - affects limbic regions and downregulates BDNF
- Pyschomotor performance - cerebral cortex depression
- Tachycardia / vasodilation (conjunctivae) - via TRPV1 receptor which stimulates Ca influx
The medulla has very low CB1 receptor expression. Why
Low CB1 expression means cannabis cannot influence cardio-respiratory control, so you can’t OD on cannabis
When can upregulation of CB receptors be regulatory?
in multiple sclerosis, pain, stroke (ischaemic vasoconstriction)
When can up regulation of CB receptors be pathological?
Fertility / obesity (obesity when up regulation of CB receptors in adipocytes)
When are agonists for CB receptors used?
To treat conditions where up regulation of CB receptors is regulatory
Give examples of CB receptor agonists
- Dronabinol - used to increase appetite in AIDS patients
- Nabilone - antiemetic drug - prevents nausea and vomiting in chemo patients
Both dronabinol and nabilone are types of THC
- Sativex - used to treat severe/moderate spasticity in multiple sclerosis patients
Name a CB receptor antagonist and its purpose
Rimonabant - anti-obesity medication but also caused depression
What percentage of cannabis elimination is gut and what is urine
Gut = 65%
Urine = 25%
What is the Half life of cannabis
7 days in tissue
