Substance use and addictions Flashcards
Give examples of drugs that may cause addiction
Alcohol
Stimulants (amphetamine, cocaine/crack, ecstasy)
Psychedelics (LCD, magic mushrooms)
Opioids (fentanyl, heroin)
Nicotine
NO
Cannabis
Ketamine
Solvents
Benzodiazepenes
What are the three types of reasons people taker drugs?
Positive reinforcement: to gain a positive state (Escapism, get high, stay awake, like it)
Negative reinforcement: to overcome an adverse state (overcome anxiety, feel better, to get to sleep , boredom)
Normal (why not, everyone does it, to fit in, rebel, curious)
What is the typical course of alcohol/drug use, harmful use and addiction?
Initial use of the substance is experimental, causing no/ limited difficulties to the user
This may develop into regular use where dependence is being developed (however patient may revert back to initial experimental state with adequate support)
Patient may develop complete dependence, a state where they need the drug to function
What is the ICD definition of harmful substance use?
The use of a substance in a way that causes damage to the user, be it to their mental or physical health, in the absence of a dependence syndrome
How does hazardous substance use differ from harmful substance use?
- Hazardous use means it’s likely to cause harm if continued use
- Moderate use → hazardous use → harmful use
What are the diagnostic criteria for dependence syndrome using ICD-10?
- Strong desire/ compulsion to take the drug
- Inability to control substance taking behaviour in terms of onset, termination or levels of use (who has control, you or the drug? when did you last have a drink/ drug?)
- State of physiological withdrawal if use is stopped or reduced (this is a negative state ranging from uncomfortable to intolerable/ life-treating so patients will take drug to get relief from it)
- Evidence of tolerance developed (patient needs to take more of the drug to achieve same effect)
- Progressive neglect of alternate interests
- Continued use of drug despite clear harm
Need to meet at least 3 of these criteria within the last 12 months to be classed as dependent
What drug causes the most harm in the UK?
Alchohol
Define addiction
Compulsive use of a drug despite harmful consequences, characterised by an inability to stop using the drug
Failure to meet work/ social/ family obligations
Tolerance/ withdrawal
Define dependence and describe how it is different from addiction
Physical adaptation to a substance
Underpins mechanisms of tolerance and withdrawal
Can be dependent on a substance without being addicted
Give 2 examples of behavioural addictions
Internet gaming disorders:
Added to ICD-11 under behavioural addictions
Is in DSM-5 under ‘conditions for further study’
Gambling disorders:
reclassified as behavioural addiction from ‘impulsive control disorder’ in DSM-5/ICD-11
What 2 factors determine a drugs addictive potential?
The speed with which a drug enters the body
The psychoactive effects of the drug
Give three examples of how a drug can be refined for more rush and addiction
Opium can be refined into injected heroin
Coca leaves can be refined into crack
Chewing tobacco is refined into cigarettes/ vape
What factors are involved in drug use and addiction?
Social and environmental factors (peer pressure, social drinking)
Drug factors
Personal factors (genetic factors, personality traits such as being impulsive/ emotionally unstable
Describe how drug addiction develops
Starts with a pre-existing vulnerability e.g. family history, young age
Initial exposure
Brain has compensatory mechanisms to maintain brain function so that the individual appears to be functioning fine despite having consumed a lot of alcohol
Individual then may either have sustained recovery if drug is stopped or cycles of remission & relapse
What is the excitatory system in the brain and what receptor does is act on?
Glutamate system
NMDA receptor
What is the inhibitory system in the brain and what receptor does is act on?
GABA-benzodiazepine system (GABA-A system)
GABA-A receptor
How does acutely drinking alcohol affect brain’s neurotransmitter systems?
There is a boost in the inhibitory system leading to anxiolysis and a state of sedation
There is a block in the excitatory system leading to memory impairment (alcoholic blackout)
How does chronic alcohol consumption affect the brain?
The brain develops neuroadaptations so that the body becomes used to the consumption of alcohol and there is no imbalance between the GABA-A and glutamate systems
There is an upregulation of the glutamate system
There is reduced function in the GABA-A system (GABA-A receptors switch subunits to be less sensitive to alcohol) leading to tolerance
Increased alcohol consumption is needed to achieve a state of sedation
What happens to chronic alcohol consumers in the absence of alcohol and how is this treated?
Imbalance- there is reduced function in the inhibitory system and up regulation of the excitatory system
This increased calcium ion binding to NMDA receptor leads to hyper excitability (seizure) and cell death (atrophy)
Treated with benzodiazepines to boost GABA function
How does acamprostate help people remain abstinent?
Reduces NMDA function by reducing glutamate
What is the function of dopamine neurotransmitter in the brain?
Involved in the ‘pleasure-reward-motivation’ system.
Where is the dopamine pleasure-reward-motivation system found in the brain?
Ventral striatum
What increases dopamine levels in the brain?
Natural rewards like food and sex
Drugs of abuse
What are the key modulators of the dopamine system in the brain?
Opioids, particularly mu opioids which mediate pleasurable effect e.g. from alcohol or endorphin rush from exercise
Also cannabinoids, GABA-B and glutamate that are also targets for treatment
How is addiction described in the context of the dopamine system?
As a reward deficient state so people take drugs to make them feel better
What drugs block dopamine reuptake?
Cocaine, amphetamines
What effects do amphetamines have on the dopamine system?
Enhances dopamine release
Blocks dopamine reuptake
What effect do other drugs e.g. alcohol, opiates, nicotine have on the dopamine system?
Increase dopamine neuron firing in ventral tegmental area (VTA) by reducing inhibition of release
What was found about the effect of giving D2 agonists on people with different levels of D2 receptors in brain?
Those who had higher levels of D2 receptors didn’t like the feeling from the D2 agonist
Those who had lower levels of D2 receptors were more likely to like the agonist
This could be because the low D2 receptor level patients have lower dopaminergic function in their natural pleasure reward system so taking a drug that increases dopamine feels good
But if you already have a good level of activity, excessive dopamine can instead cause anxiety/paranoia (e.g. like in schizophrenia excess dopamine causes psychosis)
How can the dopamine reward pathway be assessed?
- Functional MRI can be used to assess function
- It records the delay between the cue and target release
- This can indirectly measure brain response during anticipation of winning money i.e. a ‘reward’ in addiction → monetary incentive delay task
What is the effect of substance use on reward pathway in abstinent addicts?
What are the implications of this?
Substance use will blunt activation of reward system in abstinent addicts compared with control
Less reward means that the individual will continue to take substance and experience their adverse affects
In abstinent addicts, those with blunted response in the brain to ‘anticipation of reward’ are more likely to relapse
This is consistent with reward deficiency theories of addiction
How may abstinence affect reward pathway?
With enough abstinence, the response of the reward pathway can be restored to a level similar to that of controls
what regions of the brain are involved in bingeing/intoxication?
thalamus, dorsal striatum
what regions of the brain are inolved in withdrawal?
brainstem, hypothalamus
what regions of the brain are involved in craving?
prefrontal cortex,
hippocampus,
insula,
basolateral amygdala
How does reinforcement change as addiction develops?
Changes from positive to negative
As neuroadaptations develop the “highs” become less and the “lows” become greater
Therefore patients consume more of the substance in order to reach the highs/ overcome the lows
As reinforcement changes from positive to negative in substance abuse, how do these patients present in clinic?
They are in a state of fear/anxiety/aggression
This is because their access to the drug has been cut off- they are highly motivated to get it but they know they can’t
What cerebral structure is dysregulated in states of negative reinforcement in addiction?
Amygdala
What systems are affected when amygdala is dysregulated and how?
- Reward system is suppressed: reduced dopamine and mu opioid function
- Stress system is activated: consists of kappa opioid (dynorphin), noradrenaline (arousal system), corticotrophin releasing factor (stress) etc
How may we assess amygdala function?
What did we see in healthy vs polydrug and vs alcohol?
- fMRI of brain to look at amygdala
- Look at patients’ emotional processing of neutral and aversive images → these weren’t images of alcohol/drugs though
- Polydrug group had heightened reaction and found images very aversive
- Didn’t see reaction in alcohol group, maybe because they’re abstinent and have gone past initial phase of being highly reactive
- How does brain function transition as voluntary drug use changes to more habitual and compulsive drug use?
- Transition from prefrontal to striatal control over drug taking
- i.e. prefrontal ‘top-down’ control is diminished with greater striatal reward drive
- Relationship between dorsal striatum & frontal cortex becomes dysregulated
- Ventral (limbic or emotional) to dorsal (habit) striatum
- Role for memory (e.g. hippocampus) in craving the substance
How may staying abstinent reinforce an individual staying abstinent?
- Diagram shows a greater BOLD response (inhibitory response) exhibited by abstinent patients
- The longer one stays abstinent, the greater inhibitory response they can produce
- This greater inhibitory response can allow them to resist drug taking and stay sober for longer
