17. Drug dependance

Question 1

What is meant by ‘addiction’?

Answer 1

Chronic disease

Characterised by drug seeking and use that is compulsive or difficult to control, despite harmful consequences

Question 2

Define ‘drug abuse’

Answer 2

Pattern of drug use in which the users consume the substance in amounts or use methods which are directly or indirectly harmful to themselves or others

Question 3

Define ‘drug dependence’

Answer 3

An adaptive state that develops after repeated drug use - results in withdrawal symptoms upon cessation of drug use

Question 4

Define ‘drug tolerance’

Answer 4

The diminishing effect of a drug which results after repeated administration at a set dose

Question 5

Define ‘psychological dependence’

Answer 5

Dependence that involves emotional and motivational withdrawal symptoms e.g. depression, anhedonia, restlessness

Question 6

Define ‘physical dependence’

Answer 6

Dependence that involves significant physical-somatic withdrawal symptoms e.g. fatigue, nausea, seizures, pain

Question 7

What is the effect of drug use on public health?

Answer 7

Has a major impact on public health due to hospital admissions and mental illness diagnoses resulting from drug abuse

Question 8

What are the different legal classifications of drugs (illegal drugs)?

Name some drugs that fall into each category

Answer 8

Classes A to B: A represent those that are deemed most dangerous and carry the harshest legal consequences and C represent those thought to have the least capacity for harm

Class A - heroin, methadone, cocaine, crack cocaine, ecstasy, LSD, magic mushrooms
Class B - amphetamnes, barbiturates, ketamine, cannabis, codeine
Class C - anabolic steroids, benzodiazepines

Question 9

What receptors do opiates act on and how?

Answer 9

Agonists to mu and delta opioid receptors

Question 10

What receptors does cocaine act on and how?

Answer 10

Antagonist to Da, NAd and 5-HT uptake systems

Question 11

What receptors do amphetamines act on and how?

Answer 11

Monoaminergic transmission uptake systems

Question 12

What receptors does ethanol on and how?

Answer 12

Modulator of GABAa and NMDA receptors

Question 13

What receptors does nicotine act on and how?

Answer 13

Agonist to nicotinic receptors

Question 14

What receptors do cannabinoids act on and how?

Answer 14

Agonist to CB1 receptors

Question 15

What receptors do ketamine act on and how?

Answer 15

Antagonist to NMDA glutamate (excitatory) receptors

Question 16

What receptors do hallucinogens act on and how?

Answer 16

5-HT receptors

Question 17

What receptors do barbiturates and benzodiazepines act on and how?

Answer 17

Positive allosteric modulators of GABAa receptors

Question 18

Which organ is affected and undergoes change in addiction?

Answer 18

The brain

Question 19

Which factors determine the development of addiction?

Answer 19

Environment e.g. social circle smoking?
Drug-induce effects
Genetics - ability of becoming addicted to a drug and of getting over the addiction

Question 20

What is the dopamine pathway in the brain important for?

Which specific region is involved in this?

Answer 20

Dopaminergic pathways are important for the reward system e.g. the nigra striatum pathway

The ventral tegmental area (VTA) is responsible for the linkage of the dopaminergic fibres to the nucleus accumbens

Question 21

What is the ventral tegmental area?

Answer 21

Aka. The ventral tegmentum is a group of neurones located close to the midline on the floor of the midbrain

This is the origin of dopaminergic cell bodies

Question 22

Describe and explain the addiction cycle

Answer 22

Addicts go through cycles and cycles - addiction is chronic

Stage 1 - Binge/Intoxication - exposure to the substance brings you pleasure - the positive reinforcement makes you feel good
Stage 2 - Withdrawal/negative affect - the substance stops and washes away from the system - you feel awful and there is a stage of withdrawal from the experience - negative reinforcement of not taking the drug
Stage 3 - Preoccupation and anticipation - become preoccupied with how you can start to feel the pleasurable experience again and this takes you back to stage 1

Question 23

Give the cellular mechanisms that underlie why over time, people feel a need to increase their drug dosage

Answer 23

The drug results in dopaminergic release onto the dopamine receptors at the nucleus accumbens - neurones from here project straight back to the ventral tegmentum in a complete circle and they release GABA here
This results in a inhibition of the initial dopaminergic release to the accumbens neurones - simple mechanism of negative feedback
The GABA release will attempt to dampen down the activity of the dopaminergic cells and so the dosage required for the same hit will need to increase

Question 24

Name all the regions of the brain that are affected by addiction

Answer 24

Ventral tegmental area
Nucleus accumbens
Amygdala 
Insula 
Prefrontal cortex
Hippocampus 

All these regions become dysfunctional in an addicted brain - the connectivity becomes distorted

Question 25

What is the main region of the brain that is effected in addiction and what is it’s normal function?

Answer 25

Prefrontal cortex

Self-control !!
Emotional regulation 
Motivation 
Attention and flexibility 
Working memory 
Decision making
Awareness and insight
Learning and memory 
Salience attribution

Question 26

Chronic drug abuse and gene regulation

Answer 26

Get from mimi

Question 27

What effect does alcohol have on the brain and why is this different to most other drugs?

Answer 27

Alters the excitability of NMDA (glutamate) receptors and also can change the influx of Cl- ions through GABAa receptors and SO it can modulation both excitatory and inhibitory conditions - makes it such a powerful drug

NB. alcohol abuse has both an acute effect spectrum and can also lead to long term consequences

Question 28

What is the effect of alcohol on the size of the brain?

Answer 28

Alcohol abuse has also shown to lead to a shrinkage of the rain - leads to 12% less grey matter

Question 29

What are the neuronal targets of ecstasy (MDMA)?

Answer 29

5-HT uptake system
Dopamine uptake system
5-HT2 receptors
H2 histamine receptors
a2 adrenergic receptors

There is also a loss of serotonin fibres and an overall loss of serotonin innervation

Results in a pleasure sensation and an increased energy

Question 30

Which receptors do cannabinoids bind to and where are they located?

Answer 30

CB1 (g-protein coupled receptor) and CB2 receptors

CB1 - CNS
CB2 - peripheral organs and are associated with the immune system

Cannabinoids are mainly inhibitory

Question 31

What are the key stages in the management of addiction?

Answer 31

Detoxification of the drug from the body
Psychological support i.e. counselling
Medication when available e.g. for opioids, tobacco, alcohol
Evaluation and treatment for co-occuring mental health problems
Long term follow up

Question 32

What medication can be used to treat alcohol addiction?

Answer 32

Opiate antagonist nalmefene

Question 33

What medication can be used to treat nicotine addiction?

Answer 33

Varencline - a2B2 selective partial agonist at nicotine receptors