Drugs of Abuse: General/cannabis

Question 1

Why are drugs abused?

Answer 1

• they hijack the rewards system our body
• it originates at dopaminergic neurones that originate at the VTA (ventral tegmental area) and prject into the nucleus accumbens
• the release of dopamine in the nucleus accumbens stimulates the feeling of reward

Question 2

What are the routes of administration for drugs?

Answer 2

• intra nasal
• oral
• inhalation
• inject

Question 3

How rapid is the action via each route?

Answer 3

• intra nasal - mucous membrane of nasal sinuses = slow absorption
• oral - GI tract = v slow absorption
• inhalation = small airways and alveoli = rapid absorption
• injection - veins = very rapid

oral < intranasal< intravenous < inhalation

Question 4

What are the main classes of drugs of abuse?

Answer 4

• narcotics/painkillers - opiate like drugs e.g. heroin
• depressants e.g alcohol, benzodiazepines, barbiturates
• stimulants e.g. cocaine, amphetamine, caffeine, methamphetamine
• miscellaneous e.g. cannabis, ecstasy

Question 5

How many compounds exist in cannabis plants?

Answer 5

• 400 compounds

- 60 cannabinoids

Question 6

How has cannabis dosing changed over time?

Answer 6

• in the 60s and 70s there used to be about 10 mg THC in a joint
• now the amount of THC is a lot higher and there are less cannabinoids = more potent than they used to be

Question 7

What happens as you increase the dose of cannabis?

Answer 7

• as the dose goes up there is more chance of seeing prominent negative effects

Question 8

What are the main routes of administration of cannabis?

Answer 8

-oral ( only 5-15% of the drug accesses the bloodstream) - delayed onset/slow absorption
largely affected by first pass metabolism

-inhalation ( 25-35% of the drug reaches the bloodstream)

Question 9

How long do the effects of cannabis last on the brain and why?

Answer 9

• only a few hours

- it is highly perfused so the drug will reach the brain and also leave it early

Question 10

Why do cannabinoids build up in the fat?

Answer 10

-fats are very poorly perfused but cannabis is VERY lipid soluble this means that cannabinoids very slowly build up and then remain in the fat

Question 11

How long after smoking cannabis will the effects persist in the body?

Answer 11

• 30 days

there is slow leakage into the bloodsteam from the store of cannabinoids in adipose tissue

Question 12

What is the main metabolite of cannabis?

Answer 12

• 11-hydroxy-THC MORE POTENT

Question 13

How is cannabis metabolised?

Answer 13

the liver metabolises it into 11-hydroxy-THC and this is then excreted to the GIT via bile. This then recycles back around the body via enterohepatic cycling

25% is excreted in the urine

Question 14

Why is there a poor correlation between plasma cannabinoid concentration and the degree of intoxication?

Answer 14

• other metabolites will be in the blood that also have an effect
• cannabinoids in the fat will not be detected by a blood test

Question 15

What does the endogenous cannabinoid system in the body mean?

Answer 15

• the body produces various cannabinoid like substances that have various effects in the body

Question 16

Where are the cannabinoid drug receptors in the body and how do they work?

Answer 16

• CB1 in the hippocampus, cerebellum, cerebral cortex, basal ganglia
• CB2 - immune cells
• G -protein receptors negatively coupled with adenylate cyclase

Question 17

Give an example of an cannabinoid like substance that is produced?

Answer 17

anandamide

Question 18

What is the mechanism behind the feeling of euphoria?

Answer 18

• GABA usually inhibits the dopaminergic neurones from releasing dopamine and having a positive effect
• cannabis binds to a CB1 receptor and switches off GABA function

Question 19

How does cannabis abuse lead to psychosis and schizophrenia?

Answer 19

• the anterior cingulate cortex is involved in performance monitoring and behavioural adjustment
• cannabis interferes with this
• there is hypoactivity in the portion of the brain so behavioural performance adjustment is impaired

Question 20

What effect does cannabis have on food intake?

Answer 20

it increases it

Question 21

How does cannabis increase food intake?

Answer 21

• positive effect on orexigenic neurones in the lateral hypothalamus
• presynaptic inhibition of GABA increases MCH neuronal activity
• increased orexin production

Question 22

What are the peripheral effects of cannabis?

Answer 22

• immunosuppressant
• tachycardia
• vasodilation

low CB1 expression on the medulla

Question 23

Which disease is cannabis regulatory for?

Answer 23

-multiple sclerosis/pain/stroke

Question 24

Which disease is cannabis pathological for?

Answer 24

• fertility

- obesity

Question 25

What does dronabinol do?

Answer 25

• treat nausea and vomiting caused by chemotherapy

- treat loss of appetite and weight loss in people with AIDS

Question 26

What does Sativex do?

Answer 26

-treatment for elderly people with MS

Question 27

What does Rimonabant do?

Answer 27

• it is a CB receptor antagonist

anti-obesity medication