Module 1: Drug Craving and neural basis

Question 1

How is addiction defined by NIDA?

Answer 1

“a chronic, relapsing disorder, characterised by compulsive drug seeking, continued use despite harmful consequences, and long-lasting changes in the brain”.

Question 2

What are the latter changes responsible for according to the brain disease model?

Answer 2

Impaired cognitive control functions, emergence of craving and habits, which result in uncontrolled use and relapse

Question 3

Relapse rates and what can influence these?

Answer 3

70% relapse within 3 months for drugs, 30% relapse within 3 years for alcohol. There can be co-morbid factors and there can be spontaneous remission (relapse rates due to only clinical population)

Question 4

Moral model of addiction

Answer 4

Addiction seen as a sign of moral weakness, lead to those with an addiction being sent to prison or institutions

Question 5

Pharmacological model

Answer 5

The idea that addiction was attributed to the addictive substance, so instead there were countermeasures to prevent people from becoming involved with the substances. Now seen as one-sided and out-dated as the availability and use is not enough to develop an addiction

Question 6

Symptomatic model

Answer 6

Addiction not viewed as a condition itself but a symptom of underlying character neurosis or personality disorder. Treatment based on this is long-term and insight-oriented psychotherapeutic treatment

Question 7

Disease model (Jellinek)

Answer 7

Fundamental biological and psychological differences exist. Addiction involves uncontrolled used and psychical dependence (tolerance and withdrawal)

Question 8

Bio-psycho-social development model

Answer 8

here are only relative differences between addicts and non-addicts and smooth transitions between use, overuse, abuse, harmful use and addiction. The onset and ending of addiction is due to the interaction between innate vulnerability, personal development and circumstances

Question 9

Different kinds of drugs

Answer 9

• Sedatives, that tend to make you calm and relaxed. These include alcohol, barbiturates, benzodiazepines, and opiates (opium, heroin, morphine).
• Stimulants, that tend to be invigorating. These include caffeine, nicotine, amphetamine (speed), and cocaine.
• Psychedelics, that alter your state of consciousness and perception of the world around you. These include cannabis, extasy and LSD.

Question 10

How are these drugs similar?

Answer 10

They directly/indirectly result in a release of dopamine in the nucleus accumbens

Question 11

When are individuals less sensitive to rewards?

Answer 11

When they have a low density of D2 receptors in the ventral striatum. Can lead to looking for stronger stimuli to compensate for this, but D2 receptor density could also be down-regulated as a consequence of substance use (reward deficiency syndrome)

Question 12

Incentive sensitization theory

Answer 12

Drug-associated stimuli gain incentive salience, so the stimuli attract attention which leads to more wanting of the drug. This results in targeted behaviour to acquire the drug. While wanting increases, liking decreases. There can be more craving after withdrawal symptoms disappear. Dopamine in mesolimbic system is important for wanting.

Question 13

Tolerance and withdrawal symptoms

Answer 13

Tolerance is the reduction of a certain effect of a substance when administered chronically, the body/brain becomes less sensitive to it and a higher dose is needed. Withdrawal symptoms can occur with abstinence can include: anxiety, irritability, malaise, dysphoria

Question 14

Opponent-processes theory

Answer 14

A drug initially brings pleasure (positive reinforcement), but tolerance occurs and is used to avoid withdrawal symptoms (negative reinforcement)

Question 15

How has the understanding of drug use and addiction improved?

Answer 15

• identified neural circuits, common pathways across drugs
• major receptors for drugs
• biochemical cascades that follow receptor activation
• but, there is a gap in this understanding by the general public and their application in public policy

Question 16

Barriers to transferring scientific knowledge into practice

Answer 16

• stigma of using drugs, seen as weak or bad people who cannot control behaviour and gratifications (but is a compulsive disorder)
• those working in drug abuse have different ideologies

Question 17

How could public health approaches change?

Answer 17

Drug use is a vector for transmission of serious diseases, so can be improved by modifying behaviours of drug use. More education, prevention efforts, treatment and research is needed

Question 18

What was the view about addictive drugs and how is this outdated?

Answer 18

How addictive the drug was judged by the severity of withdrawal symptoms. Outdated as withdrawal symptoms can be managed with medication, and some addictive drugs do not produce severe physical symptoms. Compulsive drug-seeking and use is the most important for treatment

Question 19

Mesolimbic reward system

Answer 19

Extends from ventral tegmentum to nucleus accumbens with projections to the limbic system and orbitofrontal cortex

Question 20

How are addicted brains distinctly different from the non-addicted brain?

Answer 20

There are pervasive changes in brain function like through brain metabolic activity, receptor availability, gene expression and responsiveness to cues. There are likely common brain mechanisms underlying the addictions. A switch can lead to a state of addiction

Question 21

How can the brain change due to drug use?

Answer 21

There can be drug-induced changes which also contribute to addiction, especially mesolimbic sensitization. There is a persistent sensitization or hypersensitivity to incentive motivational effects of drugs and drug associated stimuli

Question 22

Incentive-sensitization theory

Answer 22

The incentive sensitization produces a bias of attentional processing towards the drug-associated stimuli and there is compulsive wanting for the drugs. There is association between the drug and activation of the mesolimbic brain system which leads to more sensitization. There is less liking of the drug as these mechanisms are separate. The wanting can be triggered by cues or mental representations, or contexts or mood states. Combined with impaired executive control can lead to addiction.

Question 23

What is drug sensitization?

Answer 23

Neurobiological changes in the brain mesolimbic dopamine systems and in related structures that mediate the psychological function of incentive salience. Involves an increase in drugs to elevate dopamine transmission

Question 24

Why do only some drug users become addicts?

Answer 24

Some are more susceptible which is determined by genetic, hormonal factors, gender differences, drug experiences, previous experiences with major stresses. Different drugs can all induce sensitization but to different degrees, higher doses lead to more sensitization and if there are periods of abstinence in between usage. Also by speed with which drugs reach the brain

Question 25

How does neural sensitization lead to becoming hyperreactive to drugs?

Answer 25

When exposed to drug or to drug-related cues, effects of drug cues and drugs themselves can interact

Question 26

Traditional withdrawal-based explanations of addiction

Answer 26

Drugs are first taken because they are pleasant and drugs are taken to avoid withdrawal symptoms (pleasure-pain, opponent, hedonic homeostasis etc)

Question 27

Problems with traditional withdrawal theory

Answer 27

-Withdrawal is less powerful at driving drug-taking, positive incentive processes caused by drugs and their cues more powerful. Investigated with rats given a drug to induce withdrawal, but priming a cocaine injection is more effective.
- Relapse can occur with the absence of withdrawal symptoms and cues do not produce conditioned withdrawal

Question 28

How can these anomalies be better explained?

Answer 28

Distinction between liking and wanting as the wanting increases due to neural systems mediating neural process of incentive salience but not neural systems mediating the pleasure of drugs. This can explain that sensitization-related changes persist after withdrawal ends to drive wanting drugs and so liable to relapse

Question 29

How does aberrant learning explain addiction?

Answer 29

Drugs can alter the learning process to transition to addiction and cues can predict availability of rewards. Repeated exposure can trigger neuroadaptations in reward-related neurons

Question 30

Criticisms for learning hypothesis to addiction

Answer 30

• Automatic SR habits do not become compulsive due to being well learned, as habits do not intrude and impose when doing something else. Drug use is more intentional
• addictive behaviour shows targeted flexibility and suggests a motivational component
• SR associations are important for habits in consuming drugs when they have been obtained, and SR habits can develop through dorsal striatum

Question 31

How does learning interact with incentive sensitization?

Answer 31

Once sensitization develops, its expression can be modulated by learning. The focus on drugs is produced by an interaction with incentive-salience mechanisms with associative learning mechanisms which is why sensitization can be expressed in certain contexts. Incentive sensitization can spill over to other targets which suggests a difference in wanting and learning

Question 32

Can incentive sensitization occur in other addictions?

Answer 32

Unclear about whether wanting can occur for those that have never taken drugs or medications, and no evidence for whether occurs in other disorders. But excessive wanting could drive binge eating episodes due to inherited gene variants

Question 33

How does incentive sensitization relate to cognitive dysfunction?

Answer 33

There can be changes in executive functions like how alternative outcomes are evaluated and decisions and choices made for those who take drugs

Question 34

How is incentive salience and wanting different to desire?

Answer 34

Incentive salience can be seen most in cue-triggered wanting and motivational magnet effects to be attracted to a stimuli, and can occur when there is no conscious awareness of reward. There are no declarative and explicit goals for “wanting” which differs to desire, but this can influence cognitive desires. These can disassociate at times. Can also be distinguished as “ wanting” is linked to decision utility while cognitive wants linked to predicted utility. Could be due to incentive salience being mediated by subcortical brain mechanisms while cognitive forms of desire are dependent on higher cortex-based systems

Question 35

How does an incentive stimulus differ from a normal stimulus?

Answer 35

Transforms sensory shapes, smells or sounds in attractive stimuli, it becomes difficult to avoid noticing

Question 36

When is a stimulus attributed with incentive salience?

Answer 36

• motivational magnet property so stimuli has to be approached
• wanted so people work to get them and support learning of new actions to get them (conditioned reinforcers)
• can trigger momentary peaks of intense motivation to obtain a reward

Question 37

How can compulsive be defined?

Answer 37

This is a sense of an external force to move against outcomes against the desire so seems to be internal. But a compulsive “ want” arises due to disassociation of components, so incentive salience is outside of their control and there can be contradictory desires. If the cues are in the right setting, there can be cue-triggered wanting. “ wanting” can overtake a dominant cognitive intention or desire

Question 38

What evidence can support this idea?

Answer 38

• when rats were administered a dopamine-blocking drug, this prevents “wanting” but has no effect on cognitive wants
• “wanting” can change as when a rat has elevated dopamine activation, “wanting” is expressed with cues while “ wanting” did not change. Suggests separation from cortex which mediates stable cognitive goals

Question 39

What is the criteria of substance use disorder?

Answer 39

2 of 11 features occurring within 1 year
(2-3: mild; 4-5: moderate; ≥6: severe):
1. Taking the substance in larger amounts or for longer than you’re meant to.
2. Wanting to cut down or stop using the substance but not managing to.
3. Spending a lot of time getting, using, or recovering from use of the substance.
4. Cravings and urges to use the substance.
5. Not managing to do what you should at work, home, or school because of substance use.
6. Continuing to use, even when it causes problems in relationships.
7. Giving up important social, occupational, or recreational activities because of substance use.
8. Using substances again and again, even when it puts you in danger.
9. Continuing to use, even when you know you have a physical or psychological problem that
could have been caused or made worse by the substance.
10. Needing more of the substance to get the effect you want (tolerance).
11. Development of withdrawal symptoms, which can be relieved by taking more of the substance

Question 40

Lifetime prevalence of substance use disorder in the Netherlands

Answer 40

17%, Alcohol is 12.8% and drugs is 6.6%

Question 41

Sociodemographic factors related to substance use

Answer 41

Younger age, unemployment, men, living alone, more urbanization, not income and country of origin

Question 42

Risk factors

Answer 42

• substance use by caregivers
• low refusal skills
• poor social skills
• availability
• community poverty
• aggressive behaviour in childhood
• lack of parental supervision
• early drug use
• genetic predisposition
• personality traits like impulsivity and difficulty regulating
• comorbidity

Question 43

Protective factors

Answer 43

• self-efficacy (belief in ability)
• academic performance
• parental monitoring and support
• positive relationships
• anti-drug policies
• neighborhood resources

Question 44

Barriers to seeking treatment

Answer 44

• attitudinal
• stigma
• readiness for change
• structural (do not know where to start or go)
• financial/costs

Question 45

Common triggers for substance use

Answer 45

• stressful circumstances
• pre-existing conditions
• returning to a place or person linked to drug use

Question 46

Striatum

Answer 46

A small group of subcortical structures in
the basal ganglia, including:
1. Caudate
2. Putamen
3. Nucleus Accumbens
(often referred to as ventral striatum)

Question 47

Liking

Answer 47

Hedonic experience of the substance

Question 48

Wanting

Answer 48

Extreme craving which does not have to be experienced consciously but triggered with associated cues

Question 49

How have motivational magnets been studied?

Answer 49

Through conditioned place preference paradigm. Associate certain areas with vehicle or alcohol, then revisit them, spend more time on the alcohol side. Link to VTA and increase in dopamine in NA

Question 50

How can cues becoming reinforcers be studied?

Answer 50

Through conditioned reinforcement paradigm which is that when light is linked to drugs, rats will work harder to get it by using a response to lead to the light.

Question 51

Incubation of craving

Answer 51

That craving can increase during extinction

Question 52

How has reinstated drug-seeking been operationalized?

Answer 52

Conditioning of drug with response, then extinction and reinstating it leads to more performing of that response. But can be prevented by manipulating VTA and nucleus accumbens

Question 53

How has motivation to work for drug increasing been studied?

Answer 53

Progressive ratio experiments and maximum number of response to get the substance is the break point. The number of responses needed to get the substance gradually increases and has been found to be higher for those with addiction