Science of substance misuse

Question 1

What two mechanisms are key to our misuse of substances?

Answer 1

• Tolerance
• Reward centre

Question 2

How is tolerance defined?

Answer 2

“Reduced responsiveness to a drug caused by previous administration”

It can be thought of like homeostasis, where the body wants to return to what was happening before.

Tolerance can develop in response to various drugs, such as ethanol, opioids, barbituates and benzos.

Question 3

Describe dispositional tolerance:

Answer 3

Less drug reaches the active site

• decreased rate of absorption
• increased rate of metabolism to inactive metabolites
• decreased rate of metabolism to active metabolites
• increased rate of excretion

Question 4

Describe pharmacodynamic tolerance:

Answer 4

Drug has less action at the active site

AKA tissue or functional tolerance

• down-regulation or internalisation of drug receptors
• reduced signalling downstream of drug receptors
• some other compensatory mechanism

Question 5

What is the role between drug effect and adaptive response?

Answer 5

• Say that the drug’s effect was: reduced transmitter release
• The physiological reponse: is an increased sensitivity to the transmitter, to try and negate the effect of the drug.
• However, when the drug is removed this physiological response will remain = withdrawal symptoms

This explains why in many cases the withdrawal symptoms are more less the opposite of the effect of the drug.

See image for clarification :)

Question 6

Please explain withdrawal phenonmena:

Answer 6

• The withdrawal effect of a drug is usually the reverse of the acute effect.
• Tolerance & dependence are closely linked
• Development of tolerance may lead to physical dependence in order to avoid the (unwelcome) withdrawal effects

For example

• Acute effect of opiod is constipation, and the withdrawal effect is diarrhoea (opposites)
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Question 7

Please explain briefly the reward pathway:

Answer 7

• Neurones project from the ventral tegmental area to the nucleus accumbens & prefrontal cortex
• When VTA neurones are stimulated they release dopamine is released.
• This causes a sensation of pleasure/reward.

Question 8

Why has the reward centre evolved?

Answer 8

• The reward pathway is normally activated by eating, drinking and sex
• It therefore encourages those “healthy” behaviours that lead to propagation of your genes

Question 9

How can drugs affect the reward centres?

Answer 9

Drugs can tap into the reward pathway and increase dopamine levels.

• heroin increases firing rate of dopaminergic neurones
• amphetamine increases dopamine release
• cocaine inhibits dopamine uptake
• alcohol
• This produces the psychological component of addiction - “craving”