Substance use and addictions

Question 1

How can we group reasons for taking a drug into positive and negative reinforcement?

Answer 1

• positive reinforcement= to gain positive state: escapism, get high, stay awake, like it
• ‘normal’= why not?, rebel, to fit in, curious, everyone does
• negative reinforcement= to overcome adverse state: boredom, to get to sleep, reduce anxiety, feel better

Question 2

How does experimental/recreational use of drugs lead to addiction?

Answer 2

‘like’- experimental/recreational use causes no/limited difficulties (majority of population)
‘want’- increasingly regular use–> harmful (fewer people)
‘need’- spiralling into dependence (smaller number)

Question 3

What is the ICD-10 classification of harmful substance use?

Answer 3

actual damage caused to mental or physical health of user without diagnosis of dependence syndrome
e.g. got into a fight due to alcohol, or recurrent chest infections due to smoking

N.B. hazardous use= likely to cause harm if continues at this level (one step before harmful)

Question 4

What is the ICD-10 diagnostic criteria for dependence syndrome?

Answer 4

• strong desire/sense of compulsion to take substance
• difficulties in controlling substance taking behaviour in terms of onset, termination or level of use (who has control? when did you last take it?)
• physiological withdrawal state when substance stopped or reduced–> negative state
• evidence of tolerance–> need to take more to get same effect
• progressive neglect of alternative interests
• persisting w/ substance despite clear evidence of harm
  ^3 of these in past 12 months

Question 5

What is the difference between addiction and dependence?

Answer 5

• addiction: compulsive drug use despite harmful consequences, characterised by an inability to stop using drug; failure to meet work, social or family obligations; and (depending on drug) tolerance and withdrawal
• dependence refers to physical adaptation to substance (tolerance/withdrawal)–> so can be dependent and not addicted

Question 6

What elements are involved in alcohol/drug use and addiction?

Answer 6

• genetics
• personality traits e.g. emotionally unstable
• strong family history
• social/societal
• environmental factors: price, access
• drug factors: formulation, speed of entry into brain

Question 7

What effect does acute alcohol exposure have on inhibitory and excitatory systems?

Answer 7

• enhances inhibitory GABA-A system–> sedation, anxiolytics

- blocks excitatory NMDA system–> impaired memory/alcoholic blackouts

Question 8

What effect does chronic alcohol exposure have on inhibitory and excitatory systems?

Answer 8

• reduced sensitivity of GABA-A receptor (switch in subunits) to alcohol–> reduced function of inhibitory system–> TOLERANCE
• upregulation of excitatory system (NMDA receptor)
• in absence of alcohol–> WITHDRAWAL state, as GABA and glutamate no longer in balance
  N.B. excess glutamate–> toxic inc. in Ca2+ at NMDAR leading to hyper excitability/seizures and cell death

Question 9

How do we treat alcohol withdrawal?

Answer 9

give benzodiazepines to boost GABA function to counter glutamatergic activity

Question 10

What is acamprosate?

Answer 10

medication to help people remain abstinent (sometimes given during detox)- reduces NMDA function–> reduced glutamate

potentially neuroprotective in alcoholism

Question 11

What area of the brain is involved in addiction with regards to increased levels of dopamine?

Answer 11

vental striatum

also frontal lobe

Question 12

What effect does both cocaine and amphetamine have on the dopamine synapse?

Answer 12

• they directly block the dopamine reuptake transporter–> so more dopamine in synapse
• amphetamine also enhances release of dopamine

(N.B. other drugs of abuse e.g. alcohol inc. dopamine neurone firing - indirect effect)

Question 13

How do dopamine D2 receptor levels in the brain predict someone’s response to psychostimulants?

Answer 13

higher levels of D2 receptors–> unpleasant feeling (anxiety? paranoia?)
whereas fewer receptors–> pleasurable effect- more likely to like stimulant drug

Question 14

What is the reward deficiency hypothesis in addiction?

Answer 14

blunted activation of reward system occurs in those who are more likely to become addicted- i.e. lower brain response during anticipation of winning reward e.g. money in addiction

Question 15

How does positive reinforcement change to negative as addiction/dependence develops?

Answer 15

• positive reinforcement lasts for a while then quickly goes and the ‘high’ point decreases
• negative reinforcement takes over
• motivation becomes primary driven by negative reinforcement

Question 16

What brain regions are associated with withdrawal and negative emotional states in addiction?

Answer 16

• dysregulation in amygdala
• ‘stress’ system: inc. activity in kappa dynorphin system, noradrenaline/arousal system and CRF/stress etc..
• reduced ‘reward’ system (dopamine and mu opined function)

Question 17

What change occurs in the brain from voluntary drug use to habitual and compulsive drug use?

Answer 17

• transition from prefrontal to striatal control (more striatal reward drive)
• shift from ventral (limbic or emotional) to dorsal (habit) striatum as dependence develops
• memory impacted in craving (hippocampus)