General drugs and cannibis

Question 1

What are the general pharmacodynamics of drugs?

Answer 1

• dopaminergic neurones from VTA are stimulated to release DA (reward) into NAcc

Question 2

what are the methods of admin of drugs? how fast are they?

Answer 2

• intranasal (mucous membranes of nasal sinus = slow)
• oral = very slow
• inhalational = rapid
• intravenous = rapid

Question 3

what is the fastest route to the brain? Why?

Answer 3

• inhalation

- pulmonary circuit is very short wherease IV must do systematic circuit before accessing the brain

Question 4

what are the classifications of drugs?

Answer 4

• narcoitics (painkillers): opiate like drugs e.g. Heroin
• depressants e.g. alcohol, benzodiazepines
• stimulants e.g. cocaine, amphetamine, caffeine
• miscellaneous e.g. cannabis, ecstasy (drugs have effects from multiple classes)

Question 5

describe the methods of admin in ascending order of onset of euphoria

Answer 5

• oral
• intranasal
• IV
• inhalational

Question 6

what are cannibis, hashish and hash oil?

Answer 6

• cannabis = plant
• hasish/resin = trichomes
• hash oil = solvent extract

Question 7

what does cannabis contain?

Answer 7

• over 400 compounds

- >60 are cannabinoids

Question 8

what do the positives aspects of smoking weed come from?

Answer 8

• from cannabidiol

- balance between cannabidiol vs delta9-THC

Question 9

what is the most potent cannabinoid?

Answer 9

delta9-THC

Question 10

how has the dosing of cannabis changed throughout the years?

Answer 10

• in 60’s was 10mg of THC
• now it is 150-300mg of THC
• inc. potency
• delta9-THC and cannabidiol inc.
• negative effects are more pronounced than positive

Question 11

what are the routes of admin of cannabis?

Answer 11

• oral (5-15% THC delivered): delayed onset, first pass metabolism
• inhalation (25% THC delivered)

Question 12

why does cannabis slowly accumulate in body?

Answer 12

• very lipid soluble
• builds up as fattu acid conjugates
• takes 30 days for effects to cease on body

Question 13

describe the metabolism of cannabis

Answer 13

• liver converts THC –> 11-OH-THC (more potent)
• GIT excretes 65%
• much of THC undergoes enterohepatic recycling due to lipid solubility
• urine excretes 25%

Question 14

describe the plasma conc vs degree of intoxication of cannabis

Answer 14

• THC much more concentrated in brain matter than in blood as very lipid soluble
• leads to poor correlation b/ plasma cannabinoid conc and degree of intoxication

Question 15

where are the cannabis receptors located?

Answer 15

Brain - CB1R (hippocampus, cerebellum, cortex and basal ganglia)
Peripheral: CB2R (immune cells)

Question 16

describe the cannabis receptor

Answer 16

inhibitory GPCR linked to AC

Question 17

what is the body’s version of THC?

Answer 17

endogenous anadamide

Question 18

describe how cannabis causes euphoria

Answer 18

• stimulation of Gi CB1 receptor
• inhibits release of GABA
• disinhibition
• inc. release of dopamine by inhibiting the inhibition of release of DA

Question 19

describe how cannabis causes psychosis and schizophrenia

Answer 19

• one target is ACC
• ACC involved in performance monitoring with behavioral adjustment
• cannabis causes hypoactivity in ACC

Question 20

how does cannabis act to inc. hunger?

Answer 20

2 actions on lateral hypothalamus:

• presynaptic inhibition of GABA –> inc. MCH neuronal activity
• inc. orexin production

Question 21

how does cannabis cause immunosuppression?

Answer 21

depress immune system by agonising CB2Rs on macrophaes, mast cells, B cell, T cell, NK cell

Question 22

what are the general central effects of cannabis?

Answer 22

• psychosis, schizophrenia
• food intake
• memory loss (limbic regions)
• psychomotor performance (cerebral cortex)

Question 23

what are the peripheral effects of cannabis?

Answer 23

• immunosuppressant

- tachycardia/vasodilation via TRPV1 receptors ( not CBRs) –> leads to red eyes as conjuctiva vasodilate

Question 24

why is it impossible to overdose on cannabis?

Answer 24

• medulla has a LOW CB1R expression

- means cardio-resp centre is not affected much

Question 25

when is there an upregulation of CBRs?

Answer 25

• MS/pain/stroke patients (to regulate pain)

- fertility/obesity (pathological and may contribute to obesity/infertility)

Question 26

how do drugs influence levels of delta9-THC?

Answer 26

• autoprotection: dronabinol/nabilone inc. levels and are anti-emetics in cancer, sativex treats MS pain
• autoimpairment: rimonabant dec. delta9THC, blocks feeling of hunger so anti-obesity