Drugs of Abuse 1: General/Cannabis

Question 1

Why are drugs abused?

Answer 1

They hijack the body’s natural reward pathway

Question 2

How does the reward pathway work?

Answer 2

There is a collection of dopaminergic neurones that originate in the ventral segmental area (VTA) and they project to the nucleus accumbens- dopamine release here stimulates feelings of reward and euphoria

Question 3

What causes dopamine release at the nucleus accumbens?

Answer 3

Anything that makes you feel good

Question 4

How do drugs that are snorted reach the brain?

Answer 4

Drugs go into the nasal sinus where it then diffuses across a mucus membrane into the bloodstream (venous system). It then goes back to the heart then up to the brain

Question 5

What is the slowest route of administration of a drug?

Answer 5

Oral

Question 6

What is the fastest route of administration?

Answer 6

Smoking- little difference between smoking and injecting though

Question 7

How do IV drugs reach the brain?

Answer 7

Drug goes into vein and then to heart and then to brain

Question 8

How do smoked drugs reach the brain?

Answer 8

It goes into the lungs were a lipid soluble drug will pass with ease across the alveoli. Then the drug goes into the pulmonary circulation then back to the heart and then to the brain- shorter distance than IV

Question 9

What are the 4 classes of drugs of abuse?

Answer 9

Narcotics/painkillers- opiate like drugs
Depressants (downers)- alcohol etc
Stimulants (uppers) cocaine, nicotine etc
Miscellaneous- e.g. cannabis and ecstasy

Question 10

What effect do depressants have on brain activity?

Answer 10

Slow it down

Question 11

What is an alkaloid?

Answer 11

Any of a class of nitrogenous organic compounds of plant origin which have pronounced physiological actions on humans- include drugs (morphine) and poisons (atropine)

Question 12

Which part of the cannabis sativa plant contains active cannabinoids?

Answer 12

Every part

Question 13

How many cannabinoids are there in a cannabis plant?

Answer 13

Over 60

Question 14

What is the most potent cannabinoid there is?

Answer 14

Delta-9 tetrahydrocannabinol (delta9-THC)

Question 15

What cannabinoid protects against some of the negative effects of delta9-THC?

Answer 15

Cannabidiol- it’s anti-psychotic

Question 16

How have the concentrations of delta9-THC and cannabidiol changed in recent years? What effect has this had?

Answer 16

Delta9-THC increased and cannabidiol decreased

Joints are more potent

Question 17

What are the major routes of administration of cannabis?

Answer 17

Inhalation and oral

Question 18

Why is oral administration of cannabis not very effective?

Answer 18

It is heavily affected by hepatic first pass metabolism

Question 19

When smoked, what percentage of the cannabis dose will be lost and not even reach the alveoli?

Answer 19

50%

Question 20

What percentage of cannabis dose reaches the blood normally?

Answer 20

33%

Question 21

Why does cannabis reach the brain quicker than fat?

Answer 21

The brain is very highly perfused

Question 22

Why do the peak effects of cannabis on the brain last only a couple of hours?

Answer 22

As it is so well perfused, it will leave quickly as well

Question 23

Why do cannabinoids build up in the fat slowly?

Answer 23

Cannabis is very lipid soluble- fatty acid conjugates build up

Question 24

Why are the effects of cannabis very long lasting? (how long?

Answer 24

Adipose tissue is a massive store of cannabinoids which slowly leak back into bloodstream over 30 days

Question 25

Which metabolite of cannabis is more potent than delta9-THC?

Answer 25

11-hydroxy THC

Question 26

Where is 11-hydroxy-THC produced?

Answer 26

In the liver

Question 27

How is 11-hydroxy-THC excreted?

Answer 27

In bile into the GI tract

Question 28

What can happen to 11-hydroxy-THC in the GI tract?

Answer 28

It can be reabsorbed into the enterohepatic circulation

Question 29

Why does the concentration of delta9-THC in the blood give a poor measure of the degree of intoxication?

Answer 29

11-hydroxy-THC can exert toxic effects as well as other metabolites Cannabinoids also leak out of the fat into the blood

Question 30

When are peak cannabinoid levels in the fat reached?

Answer 30

After around 5 days

Question 31

What endogenous cannabinoid receptors are there and where are they found?

Answer 31

CB1- Brain | CB2- Peripheral cannabinoid receptors found on immune cells

Question 32

What sort of receptor are cannabinoid receptors?

Answer 32

G-protein coupled that are negatively coupled with adenylate cyclase

Question 33

Why is cannabis classified as a depressant?

Answer 33

It slows down cellular activity by depressing the action of adenylate cyclase

Question 34

What is special about cannabinoid receptors in the brain?

Answer 34

They are the most prevalent G-protein coupled receptor in the brain

Question 35

What is an example of an endogenous cannabinoid like substance?

Answer 35

Anandamide

Question 36

What effect does GABA have on central reward pathway?

Answer 36

It has a negative influence on dopaminergic neurones of central reward pathway which prevents reward system from permanently firing

Question 37

If your brain wants you to feel reward, what does it do?

Answer 37

It inhibits GABA

Question 38

How does cannabis have an effect on the central reward pathway?

Answer 38

It binds to CB1 receptors in GABA neurones and switches off GABA function leading to euphoria

Question 39

Who are more vulnerable to psychotic effects of cannabis?

Answer 39

Younger people

Question 40

What is an important part of the brain that cannabis interacts with which is normally used in performance monitoring with behavioural adjustment?

Answer 40

Anterior cingulate cortex

Question 41

How does cannabis interact with anterior cingulate cortex?

Answer 41

Causes hypoactivity in the ACC

Question 42

How does cannabis stimulate food intake?

Answer 42

It has a positive effect on neurones in lateral hypothalamus which are involved in appetite and stimulating hunger

Question 43

What neurones are involved in stimulating hunger?

Answer 43

Orexinergic and melanin concentrating hormones

Question 44

How does cannabis have an effect on MCH neurones?

Answer 44

It inhibits GABA neurones which normally have an inhibitory influence on MCH neurones but this is removed by cannabis

Question 45

What else does cannabis seem to directly stimulate in terms of appetite stimulation?

Answer 45

Orexin production which is an appetite stimulating hormone

Question 46

What effect does cannabis have on the immune system?

Answer 46

It is a very potent immunosuppressant- | Negative effects on number of immune cells- decreases B and T cell numbers and decreases cytolytic activity of NK cells

Question 47

How does cannabis cause memory loss?

Answer 47

It affects the limbic regions - depressive effects on hippocampus in particular will lead to amnestic effects Decreases effects of BDNF

Question 48

What is BDNF?

Answer 48

Brain derived neurotrophic factor- important peptide in the hippocampus that allows the formation of memories

Question 49

How does cannabis affect psychomotor performance?

Answer 49

It causes depression of the cerebral cortex

Question 50

How does cannabis have cardiovascular effects?

Answer 50

It activates the TRPV1 receptor which leads to calcium influx and can cause tachycardia

Question 51

Why do the eyes become bloodshot?

Answer 51

Vasodilation occurs particularly in conjunctivae

Question 52

Why can't cannabis kill you?

Answer 52

CB1 receptors are very prevalent in the brain but their concentration in the medulla is very low and the medulla is responsible for controlling cardio-respiratory function so it can't really be affected by cannabis use

Question 53

What happens to CB receptors in a number of disease states?

Answer 53

They're upregulated

Question 54

What will upregulation of CB receptors in adipocytes lead to?

Answer 54

Obesity

Question 55

What are CB agonists mainly used to treat?

Answer 55

Anti-emetics like dronabinol and nabilone | Chemotherapy patients to reduce nausea

Question 56

What is dronabinol used to treat in people with AIDs?

Answer 56

Loss of appetite and weight loss

Question 57

What is sativex used to treat?

Answer 57

Symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis

Question 58

What is rimonabant?

Answer 58

CB receptor antagonist which can be used as anti-obesity medication