Substance Abuse and Addictions

Question 1

Define Harmful Substance Use

Answer 1

Actual damage should have been caused to the mental or physical health of the user in the absence of diagnosis of dependence syndrome.

Question 2

Define Hazardous Use

Answer 2

Likely to cause harm if continued at this level

Question 3

What are the criteria for Dependence Syndrome?

Answer 3

a strong desire or sense of compulsion to take the substance
difficulties in controlling substance taking behaviour in terms of its onset, termination, or levels of use
who has control, you or ‘the drug/behaviour’?
when did you last have a drink/drug?

a physiological withdrawal state when substance use has stopped or been reduced
- a ‘negative’ state (from uncomfortable to intolerable) so user takes drug/alcohol to ger relief from it or ‘treat’ it
evidence of tolerance: need to take more to get same effect

progressive neglect of alternative interests
persisting with substance use despite clear evidence of overtly harmful consequences

Question 4

Define Addiction

Answer 4

compulsive drug use despite harmful consequences, characterized by an inability to stop using a drug; failure to meet work, social, or family obligations; and, (depending on the drug) tolerance and withdrawal.

Question 5

Define Dependence

Answer 5

dependence refers to a physical adaptation to a substance
Tolerance/withdrawal
Eg opioid, benzodiazepine, alcohol
So can be dependent and not addicted

Question 6

What are some common Behavioural Disorders?

Answer 6

Gambling Disorder

Internet Gaming Disorder

Question 7

How many people drink more than 14 units?

Answer 7

21%
6% Dependent
10.4 million drink at a level that increases their risk of health problems

Question 8

What symptoms characterize Dependence?

Answer 8

Tolerance & Withdrawal

Question 9

What is the relationship between faster brain entry and addiction?

Answer 9

Faster brain entry = more “rush” and more addiction Faster onset related to speed of reaching the brain, crossing the blood-brain barrier, lipophylic.

Question 10

What is the journey from alcohol use to addiction?

Answer 10

Pre-existing vulnerability; Family history, age

Drug exposure; Compensatory neurpoadaptations to maintain brain function

Question 11

What is the Brain’s Excitatory system?

Answer 11

Glutamate system

NMDA Receptor

Question 12

What is the Brain’s Inhibitory System?

Answer 12

GABA-benzodizepine
(GABA-A) System
Sedation
Anxiolysis

Question 13

What does alcohol do to the brain?

Answer 13

Alcohol alters the balance between brain’s inhibitory and excitatory system

Question 14

What happens to the GABA-A system, acutely, when you drink alcohol?

Answer 14

Boosts Inhibitory activity, more benzodiazepine coupling, while at the same time blocking excitatory system (impaired memory)

At the same time you have upregulation of the NMDA System so you have a new balance

Question 15

What ar the adaptations to chronic alcohol use?

Answer 15

Reduces GABA-A system sensitivity, subtype switched to one that is less sensitive to alcohol.

Question 16

What is one of the genetic underpinnings of alcohol?

Answer 16

You have a less sensitive GABA receptor

Question 17

What gives you the symptoms of alcohol withdrawal?

Answer 17

Disturbance to this system means you have a downregulated inhibitory system, and an upregulated excitatory system, this imbalance causes alot of the toxic side effects.

Question 18

How can you get a seizure as a result of alcohol withdrawal?

Answer 18

Disturbance in system balance
NMDA Upregulation
NMDA is a Ca channel
More calcium channels open
Hyperexcitability can lead to seizures

Question 19

Why is benzodiazepine given as a treatment?

Answer 19

Boost the GABA system to achieve a balance

Question 20

What drug reduces NMDA function?

Answer 20

Acamprosate is a medication to help people remain abstinent – it reduces NMDA function

Question 21

What is a key modulator of the dopamine pathway?

Answer 21

A key modulator is opioid system
– particularly mu opioid that 
mediates pleasurable effects (eg 
of alcohol, ‘endorphin ‘rush’); 
others include GABA-B, cannabinoids, 
glutamate etc that are targets 
for treatment

Question 22

What can addiction be conceptualized as?

Answer 22

Award Deficient state

Question 23

Describe the dopamine pathway?

Answer 23

Dopamine released, attatches onto receptor on post-synaptic cell, dopamine reutpake in presynaptic terminal.

Drugs such as cocaine block re-uptake, Amphetamine releases more dopamine. they directly block re-uptake which makes them so potent.

Other drugs increase dopamine neuron firing.

Question 24

How can you predict people liking a drug’s effects?

Answer 24

Less D2 receptors, more pleasant feeling to stimulant

Question 25

What is the relationship between Higher activity in the reward pathway and abstinence?

Answer 25

in abstinent addicts, those with blunted response in the brain to ‘anticipation of reward’ are more likely to relapse
consistent with ‘reward deficiency’ theories of addiction

Question 26

What are the three stages of negative pathways?

Answer 26

Binge/intoxication
Withdrawal/Negative affect
Preoccupation/Anticipation craving

Question 27

What is involved in the Withdrawal/Negative affect stage?

Answer 27

Amygdala involved, Hypothalamus + Brainstem effectors (autonomic/somatic). Disregulation of the amygdala IS KEY, hormones peptides go into oeride.

Question 28

How do you go from positive to negative drug effects?

Answer 28

Become more tolerant
High gets less, withdrawal becomes bigger, more about overcoming negative state than getting high. Motivation is primarily driven by negative enforcement

Question 29

What are the systems associated with negative emotional states in addiction?

Answer 29

The ‘stress’ system: increased activity in many including kappa opioid (dynorphin), noradrenaline (arousal system) CRF (stress) etc

Question 30

What are the systems involved in the positive emotional states of alcohol?

Answer 30

The ‘reward’ system:

reduced dopamine and mu opioid function

Question 31

How do you assess amygdalar function with fMRI?

Answer 31

Emotional processing of aversive images

Heightened brain response in left amygdala in abstinent polydrug addicts to aversive images but not in alcoholism

Question 32

What transition is involved from voluntary to compulsive drug use?

Answer 32

Change from voluntary drug use to more habitual and compulsive drug use involves transition from:

prefrontal to striatal control over drug taking
i.e. prefrontal ‘top-down’ control is diminished with greater striatal reward drive
ventral (limbic or emotional) to dorsal (habit) striatum.

Role for ‘memory’ (eg hippocampus) in craving

Question 33

How do you assess neurocircuitry involved in inhibitory control with fMRI?

Answer 33

go-nogo task

Question 34

What is the response in alcoholics with greater abstinence?

Answer 34

Greater response in frontal pole/inferior frontal gyrus during inhibiting response in abstinent alcoholics:
greater response associated with longer abstinence