drugs of abuse- general/cannabis

Question 1

general mechanism of these drugs

Answer 1

dopaminergic neurones from the ventral tegmental area, projecting to the nucleus accumbens in the ventral striatum, causing dopamine release

Question 2

routes of administration and speeds and why

Answer 2

intranasal (snort), oral (eat), inhalation (smoke), intravenous (inject) snort- mucous membranes of nasal sinuses (gets into venous system but has to travel to heart): SLOW eat- GI tract: VERY SLOW ie minutes inject- veins: RAPID (but still has to go to pulmonary) smoke: alveoli: VERY RAPID (as immediately gets to pulmonary, then arteries) ie secs

Question 3

classification of drugs

Answer 3

nacrotics/painkillers- opiates ie heroin/morphine depressants- alcohol, benzodiazepines, barbiturates (slow things down) stimulants- cocaine, amphetamine, metamphetamine (meth), caffeine miscellaneous- eg cannabis

Question 4

what’s in cannabis- different types of weed and possible negative effect

Answer 4

has protective cannabidiol, and delta 9 THC normal weed has 10mg THC, new skunkweed has 150mg THC to have stronger effects: may lead to negative effects, as skunkweed has less protective cannabidiol

Question 5

pharmacokinetics of cannabis- types of administration

Answer 5

oral- 5 to 15% active due to slow absorption/first pass metabolism inhalation- 25-35% (most exhaled)

Question 6

pharmacokinetics of cannabis- major property and accumulation

Answer 6

very lipid soluble- gets to blood, brain and high perfusion tissues fast, and leaves fast as well, but because lipid soluble, slowly accumulates in poorly perfused fatty issue, leading to heavy accumulation in chronic users

Question 7

pharmacokinetics of cannabis- liver and gut

Answer 7

converted via phase q into 11-hydroxy-THC (even more potent than THC) majority excreted via bile in gut- problem as lipid soluble, so easily diffuses back into blood (enterohepatic cycling)- some excreted via urine

Question 8

relationship between plasma cannabis conc and amount of intoxication

Answer 8

plasma cannabis conc. doesn’t tell you degree of intoxication, as doesn’t tell us 11-hydroxy-THC level in fatty tissue ie brain or how much enterohepatic cycling has occurred brain mostly fat so lot can accumulate there- thus blood can show low THC and hydroxy-THC, but levels in brain can show high levels

Question 9

how long after smoking cannabis cig will it be in blood

Answer 9

30 days, as although blood cannabis levels go down rapidly, cannabis that gets into blood SLOWLY leaks out into blood

Question 10

types of receptors that cannabis acts on

Answer 10

cannabinoid receptors called CB1 (central as in brain) and CB2 (peripheral- in immune cells)

Question 11

why cannabis a depressant- relate to mechanism

Answer 11

G protein mediated inhibition on adenylate cyclase= less cellular activity

Question 12

endogenous substance ie in body that has same mechanism as cannabis

Answer 12

anandamide

Question 13

mechanism for euphoria of cannabis

Answer 13

binds to CB1 receptor on a GABA neurone, INHIBITING GABA GABA inhibits dopaminergic pathway from VTA to NA, so if inhibited, this pathway is enhanced

Question 14

mechanism of cannabis for psychosis/ schizophrenia

Answer 14

anterior cingulate corex involved in error detection, and changing behaviour depending on the situation cannabis users have less activity there= possible psychosis and schizophrenia (doing things which may be behaviourally inappropriate/ hallucinations)

Question 15

DIAGRAM mechanisms of cannabis for food intake

Answer 15

orexigenic neurones (ie AgRP) enhanced: they act on lateral hypothalamus, which increases MCH neuronal activity and increases orexin production inhibits GABA, which inhibits MCH, thus MCH enhanced= more hungry orexin binds to CB1= more hungry

Question 16

mechanisms of cannabis as immunosurpressants

Answer 16

acts on CB2 receptors present on cells like B/T cells, inhibiting them

Question 17

effects of cannabis- central and peripheral

Answer 17

psychosis/schiz food intake memory loos (inhibitory on hippocampus due to less BDNF) less psychomotor performance ie general performance (inhibitory on cerebral cortex) peripheral- immunosurpressant, tachycardia/vasodilation (bloodshot eyes),

Question 18

effect of cannabis on medulla and thus benefit

Answer 18

low CB1 receptors in medulla, so can’t have much effect in medulla good as medulla needed for cardioresp control, so because doesn’t effect medulla, can’t die from cannabis

Question 19

effect of cannabis in health and drugs

Answer 19

in MS/pain/stroke, CB receptors go up, thus drugs that +VE act on CB receptor used for these conditions- SATIVEX, DRONABINOL AND NABILONE

Question 20

effect of cannabis in disease and drug

Answer 20

in fertility/obesity, CB receptors go up, which can worsen these pathologies- thus drug that INHIBITS CB receptor used- RIMONABANT

Question 21

half life of cannabis in tissue

Answer 21

7 days