drugs of abuse- CANNABIS Flashcards
describe the reward pathways in the brain activated by drugs of abuse?
a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain, to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle.
what are some common methods of taking drugs of abuse? and their pharmacokinetics
intra nasal (snort)- slow absorption
oral (eat)- very slow absorption
inhalation (smoke)- rapid absorption
intravenous (inject)-rapid absorption
which route of drug administration will lead to the fastest drug affect on the brain?
inhalation
what are the different classifications of drugs of abuse and give examples for each?
narcotics/ pain killers eg opiates
depressants eg. alcohol, benzodiazepines(valium)
stimulants eg. cocaine, amphetamine, meth
miscellaneous eg. cannabis, MDMA
what are the pharmacokinetics of cannabis?
oral-
5-15% bioavailability
delayed onset
fair amount of first pass metabolism before it even gets to systemic circulation
inhalation-
25-35% bioavailability
when you inhale, most of the time you exhale 50% back out again. then of the remaining 50% you need to inhale it deep into the lungs to the alveoli
very lipid soluble
accumulates into poorly perfused fat tissue
in chronic cannabis use you get a huge accumulation of cannabis in the fat tissue
how is cannabis metabolised and removed from body?
metabolised in the liver to 11-hydroxy-THC (phase 1 metabolite which is very potent)
excretion of cannabis in the GIT- bile enterohepatic recycling
25% excreted in urine
how long is cannabis detectable in the body after smoking a cannabis cigarette?
30 days
how does cannabis carry out its effects? pharmacodynamics
cannabinoid receptors in the body
2 classes
CB1 receptors found in the hippocampus/cerebellum/cortex/basal ganglia
CB2r found on immune cells
inhibitory g protein coupled receptors
down regulates adenyl cyclase
CB1r stimulates GABA neurones which reduces reward pathway
cannabis binds to the CB1r
CB1r down regulates GABA neurones
leading to an increase in the reward pathway firing
DISINHIBITION
how can psychosis occur in cannabis users?
the anterior cingulate cortex (ACC) is involved in performance monitoring with behavioural adjustments in order to involve losses
drives behaviour to get best out comes
in cannabis users there is reduced activity in the ACC
so ability to monitor and change behaviour decreases
how does cannabis stimulate food intake?
presynaptic inhibition of GABA increases MCH neuronal activity in lateral hypothalamus, which has a positive effect on food seeking behaviour
increases orexin production which has a positive effect on food seeking behaviour
how does cannabis act as an immunosuppressant?
CB2 receptors present on most immune cell types
cannabis suppresses activity of these cells
what is the relevance of low CB1 receptor expression in the medulla?
this is where the cardio-respiratory system is controlled
drugs that have an effect on this region can have very dangerous effects–> cardio-resp failure
cannabis is a much safer drug than alcohol as it does not effect this area. you cant overdose on cannabis to the point of death.
what are the medical uses of cannabis?
in certain disease states, CB1 receptors increase (MS, stroke) and shown to have a positive effect.
cannabis decreases fertility- reduces testosterone, inhibits pituitary gonadal control, reduces sperm formation
what drugs are CB1 receptor agonists?
Dronabinol- stimulate appetite in AIDS patients, anti emetics
sativex- used in MS, neuropathic pain
give an example of a CB1 receptor antagonist
Rimonabant
anti obesity agent
decreases weight
no longer available as increase in depression and suicide incidents
