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LCRS Pharmacology and Therapeutics > Drugs of Abuse 1: General/Cannabis > Flashcards

Drugs of Abuse 1: General/Cannabis Flashcards

1
Q

Why are drugs abused?

A

They hijack the body’s natural reward pathway

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2
Q

How does the reward pathway work?

A

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

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3
Q

What causes dopamine release at the nucleus accumbens?

A

Anything that makes you feel good

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4
Q

How do drugs that are snorted reach the brain?

A

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

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5
Q

What is the slowest route of administration of a drug?

A

Oral

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6
Q

What is the fastest route of administration?

A

Smoking- little difference between smoking and injecting though

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7
Q

How do IV drugs reach the brain?

A

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

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8
Q

How do smoked drugs reach the brain?

A

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

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9
Q

What are the 4 classes of drugs of abuse?

A

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

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10
Q

What effect do depressants have on brain activity?

A

Slow it down

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11
Q

What is an alkaloid?

A

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

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12
Q

Which part of the cannabis sativa plant contains active cannabinoids?

A

Every part

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13
Q

How many cannabinoids are there in a cannabis plant?

A

Over 60

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14
Q

What is the most potent cannabinoid there is?

A

Delta-9 tetrahydrocannabinol (delta9-THC)

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15
Q

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

A

Cannabidiol- it’s anti-psychotic

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16
Q

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

A

Delta9-THC increased and cannabidiol decreased

Joints are more potent

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17
Q

What are the major routes of administration of cannabis?

A

Inhalation and oral

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18
Q

Why is oral administration of cannabis not very effective?

A

It is heavily affected by hepatic first pass metabolism

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19
Q

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

A

50%

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20
Q

What percentage of cannabis dose reaches the blood normally?

A

33%

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21
Q

Why does cannabis reach the brain quicker than fat?

A

The brain is very highly perfused

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22
Q

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

A

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

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23
Q

Why do cannabinoids build up in the fat slowly?

A

Cannabis is very lipid soluble- fatty acid conjugates build up

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24
Q

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

A

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

25
Q

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

A

11-hydroxy THC

26
Q

Where is 11-hydroxy-THC produced?

A

In the liver

27
Q

How is 11-hydroxy-THC excreted?

A

In bile into the GI tract

28
Q

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

A

It can be reabsorbed into the enterohepatic circulation

29
Q

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

A

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

30
Q

When are peak cannabinoid levels in the fat reached?

A

After around 5 days

31
Q

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

A

CB1- Brain

CB2- Peripheral cannabinoid receptors found on immune cells

32
Q

What sort of receptor are cannabinoid receptors?

A

G-protein coupled that are negatively coupled with adenylate cyclase

33
Q

Why is cannabis classified as a depressant?

A

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

34
Q

What is special about cannabinoid receptors in the brain?

A

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

35
Q

What is an example of an endogenous cannabinoid like substance?

A

Anandamide

36
Q

What effect does GABA have on central reward pathway?

A

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

37
Q

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

A

It inhibits GABA

38
Q

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

A

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

39
Q

Who are more vulnerable to psychotic effects of cannabis?

A

Younger people

40
Q

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

A

Anterior cingulate cortex

41
Q

How does cannabis interact with anterior cingulate cortex?

A

Causes hypoactivity in the ACC

42
Q

How does cannabis stimulate food intake?

A

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

43
Q

What neurones are involved in stimulating hunger?

A

Orexinergic and melanin concentrating hormones

44
Q

How does cannabis have an effect on MCH neurones?

A

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

45
Q

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

A

Orexin production which is an appetite stimulating hormone

46
Q

What effect does cannabis have on the immune system?

A

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

47
Q

How does cannabis cause memory loss?

A

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

48
Q

What is BDNF?

A

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

49
Q

How does cannabis affect psychomotor performance?

A

It causes depression of the cerebral cortex

50
Q

How does cannabis have cardiovascular effects?

A

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

51
Q

Why do the eyes become bloodshot?

A

Vasodilation occurs particularly in conjunctivae

52
Q

Why can’t cannabis kill you?

A

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

53
Q

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

A

They’re upregulated

54
Q

What will upregulation of CB receptors in adipocytes lead to?

A

Obesity

55
Q

What are CB agonists mainly used to treat?

A

Anti-emetics like dronabinol and nabilone

Chemotherapy patients to reduce nausea

56
Q

What is dronabinol used to treat in people with AIDs?

A

Loss of appetite and weight loss

57
Q

What is sativex used to treat?

A

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

58
Q

What is rimonabant?

A

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

LCRS Pharmacology and Therapeutics (33 decks)

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