Addiction

Question 1

What is addiction? (Criteria and definition)

Answer 1

• Addiction is a clinically-impairing (meaning, the individual cannot function without the substance) pattern of inflexible reward pursuit and consumption
• The patient must participate actively in “getting” this disorder (like type 2 diabetes or cardiovascular disease)

Question 2

What factors influence susceptibility for addiction?

Answer 2

Both genetic and environmental factors influence susceptibility

Question 3

What is addiction best understood as?

Answer 3

• Best understood as a clinical brain disorder with observable physiological manifestations that underlie pathological aspects of behavior

Question 4

What are the four stages of drug addiction?

Answer 4

• Use
• Heavy Use
• Early dependence
• Late dependence/Neuroadaptation

Question 5

How is addiction related to positive/negative reinforcement?

Answer 5

As use disorder progresses, negative reinforcement increases while positive reinforcement decreases

Question 6

What is the cycle of addiction?

Answer 6

• Initial use, then abstinence (withstanding from drug with possible withdrawal symptoms), then relapse.
• This cycle continues, leading to the progressive stages of addiction.
• Most begin with a balanced mood, but when taking the drug experience high/euphoria… then experience mild withdrawal. Overtime, euphoria magnitude decreases as magnitude of withdrawal increases. This continues until no euphoria is reached (considered late dependence with significant neuroadaptations present)

Question 7

What is the definition of substance use disorder according to the DSM-5?

Answer 7

“Substance use disorder descrbes a problematic pattern of using alcohol or another substance that results in impairment in daily life or noticeable distress”

Question 8

How many symptoms do you need for mild, moderate, and severe SUD (according to DSM-5)

Answer 8

• 2-3 symptoms: mild
• 4-5 symptoms: moderate
• 6+: severe

Question 9

How many total symptoms are there for SUD in the DSM and what are they categorized under?

Answer 9

• Physical dependence
• loss of control
• clinical impairment

Question 10

What are the physical dependence symptoms of SUDs?

Answer 10

• “Craving” the substance
• Building up a tolerance to the substance: either needing to use noticeably larger amounts over time to get the desired effect, or noticing less of an effect over time after repeated use of the same amount
• Experiencing withdrawal symptoms after stopping use (this increases as you use over time)

Question 11

Loss of control symptoms

Answer 11

• Consuming more substance than originally intended
• Worrying about stopping or consistently failed efforts to control one’s use
• Spending a large amount of time using, or doing whatever is needed to obtain them
• Continuing the use of a substance despite health problems caused or worsened by it

Question 12

Clinical impairment symptoms

Answer 12

• Use of the substance results in failure to “fulfill major role obligations” (home, work, or school)
• Continuing the use of a substance despite its having negative effects in relationships with others
• Repeated use of the substance in a dangerous situation
• Giving up/reducing activities in a person’s life because of the substance use

Question 13

SUD Manifestations Ilicit

Answer 13

• Narcotics
• Hallucinogens
• Stimulants
• Cannabis (in most states)

Question 14

SUD manifestations licit

Answer 14

• Cigarettes
• Alcohol
• Cannabis (legal in over 20+ states and DC)

Question 15

Manifestations- nonchemical

Answer 15

• Gambling disorder (in DSM5)
• Internet gaming disorder (possible)
• Food, porn, sex, shopping, exercise (under study)

Question 16

What age group misuses alcohol the most?

Answer 16

Ages 26+, probably because they can legally (66.5%)

Question 17

What age group misuses weed the most?

Answer 17

12-17 year olds have highest prevalence

Question 18

What are the main effects with alcohol use disorder?

Answer 18

• Loss of control over alcohol drinking
• Negative emotions when not drinking
• Have to drink more for the same effects

Question 19

Alcohol use deciles (per week)

Answer 19

• 1-3 decile: 0 drinks
• 4 decile: 0.02 drinks
• 5 decile: 0.14 drinks
• 6 decile: .63 drinks
• 7 decile: 2.17 drinks
• 8 decile: 6.25 drinks
• 9 deciles: 15.28 drinks
• 10 decile: 73.85 drinks

Question 20

What are the risk factors for alcohol use disorder?

Answer 20

• environment
• genetic predisposition
• early traumatic exposure

Question 21

What are other risk factors for SUDs?

Answer 21

• Men»_space; women
• Adolescents»_space; adults
• Co-morbidity with other psychiatric illnesses
• Pain disorders and other somatic diseases

Question 22

Enviornmental risk factors: What does exposure to adverse events during early-life and adolescence increase the risks of?

Answer 22

• affective disorders
• increased risk of alc and substance use disorder

Question 23

What is an important concept about drugs?

Answer 23

• Drugs are chemical ligands that interact with brain neurotransmitter systems and that can change the way people feel by altering neural signaling

Question 24

Drugs as a stimulus

Answer 24

• When consumed, drugs produce internal feeling states/stimulus effects (positive, negative, mixture)… ex. cocaine produces euphria, energy, sympathomimetic activation and anxiety
• These stimulus effects are due to the pharmacological actions of the drug (what receptors the drugs interacts with)
• Liking the positive reinforcing stimulus effects of the drug, or disliking the aversive effects, is not “learned” (so the drugs act as unconditioned stimuli)
• This involves the mesolimbic dopamine system

Question 25

What is dopamine?

Answer 25

* A NT released during a happy event or in the presence of a rewarding stimulus * Both rewarding and reinforcing

Question 26

What are the two dopamine pathways?

Answer 26

1. Substantia nigra to caudate; motor 2. VTA to nucleus accumbens; mesolimbic system

Question 27

Mesolimbic dopamine system: VTA

Answer 27

* dopamine is produced here and flows outward along neurons distributed throughout the brain's reward system * activated when there is a pleasure/rewarding/reinforcing stimulus present, and then releases dopamine to the NA

Question 28

Mesolimbic dopamine system: Nucleus Accumbens (NAc)

Answer 28

* amplifies the response to pleasure, amplifying rewarding as a result of the dopamine flowing there * involved in stress processing, affect/emotion driven

Question 29

At the synapse (between VTA and NAc)

Answer 29

* Where everything that happens in drug addiction occurs (junction between VTA and NAc) * In a typical person, certain amount of dopamine is released upon stimulation * When drugs are present, exacerbated release of dopamine from the presynaptic terminal, getting way more dopamine release and increasing the levels of DA

Question 30

What neuroadaptations occur after frequent drug use?

Answer 30

* PET imaging shows decreased dopamine D2 receptors in addicts (downregulated) * This is beyond the effect of just the release of NTs

Question 31

How we figure out dopamine was important in SUDs?

Answer 31

* 6-OHDA= neurotoxin that kills catecholaminergic neurons and/or their terminals * When injected in the medial forebrain bundle, it changes cocaine intake behavior in rats * Animals with 6-OHDA lesions (which causes dopamine depletions within the ventral striatum aka NAc) reduce cocaine taking as it reduces dopamine availability making the drug not feel reinforcing ## Footnote SHAM lesion as control: same surgery but saline or artificial CSF injected

Question 32

Is addiction learning?

Answer 32

* Drugs naturally have unconditioned stimulus properties (you feel the effects no matter what, don't have to lern the biological response) * However, because they drive a biological response, they suppport learning. If you like what you feel, you will repeat the behavior (drug intake/press lever). Addiction is dependent on action outcome being positive.

Question 33

Addiction as learning from a society perspective

Answer 33

* In our society, we associate awards with celebration (and alcohol), now this is a conditioned reponse (drug paired cues) * Drug associated cuse can gain "incentive value," including places and smells (associative learning) * Ex. Before having starbucks, no repsonse to seeing cup. After enjoying a starbucks drink, now when you see the cup you want the drink. A cup with previously not incentive value now has incentive value

Question 34

Drug paired cues

Answer 34

* drugs can be the unconditioned stimulus in a stimulus-stimulus association * Drug associated cues gain incentive value and elicit craving * Cues include the sight of the drug and paraphernalia, people with whom drugs are used, places where drugs are used, smell and/or taste of drug

Question 35

basal ganglia function in SUD

Answer 35

learning and memory

Question 36

Extended amygdala SUD function

Answer 36

reward and motivation, includes the NAc (which sits at the intersection of the basal ganglia and extended amygdala circuit)

Question 37

PFC area SUD function

Answer 37

control over behavior

Question 38

What is the larger story of the brain involvement w SUDs, beyond the mesolimbic dopamine pathway?

Answer 38

* First, you need the rewarding motivation to get the substance (if not reinforcing no one would use the substance again)... reward and motivation/extended amygdala * Then, as a result you learn what makes you feel good and bad (learning and memory portion/basal ganglia) * Finally, you exert control (you wouldn't drink 5 cups of coffee in a row even if dependent on caffeine)... control over behavior PFC

Question 39

Drug paired cues study

Answer 39

* Showing cocain addiction patients pictures of things that remind them of cocain dramatically increases blood flow in the amygdala and the anterior cingulate cortex * Amygdala is the fear, anxiety of the brain... activation because the individual cannot use the drug and are craving to a great degree * Not sure what is happening with the anterior cingulate cortex

Question 40

Instrumental learning and drugs

Answer 40

* because drugs are rewards, they support instrumental learning * actions associated w drug intake are reinforced, occurring with increasingly higher probability

Question 41

Instrumental learning study

Answer 41

* Experiment meausred dopamine on rats who can activate cocaine via pump attached to lever * With cocaine infusion, dopamine increases for a coulple of hours before it dies down * Because cocaine elevated dopamine and dopamine is generally reinforcing, it drives the positive behavior. Rat learns to associate pushing the lever to a good feeling

Question 42

Tolerance/non-associative learning

Answer 42

* not related to lever or anything like that * certain aspects of the drug's effect diminish with repeated intake * tolerance to the rewarding effects is a common phenomena | part of DSM criteria

Question 43

Non-associative learning study

Answer 43

* rats given chronic access to cocaine will show less of an effect to dopamine reuptake inhibition * cocaine is no longer as effective in blocking dopamine transporters * or, dopamine receptors have down regulated

Question 44

What causes compulsive habit formation?

Answer 44

* because people suffer from tolerance, it becomes habitual * people will go back and want to feel the high level, so they go back to the drug * End up taking the drug every morning or every evening, now it is a habit

Question 45

What is happening neurologically during compulsive habit formation? Research study

Answer 45

* Measuring dopamine in vivo (live) rats. One electrode placed in the ventral striatum (NAc) and another in the dorsolateral striatum (caudate). Rats trained to self-administer cocaine, happening over a period of three weeks * NAc (ventral striatum) affect: Week 1 get really good response of dopamine as soon as cocaine is self-administered. Week 2 slight reduction in response. Week 3, even bigger reduction, around half of first week. Cocaine is no longer effective in elevating dopamine levels * Caudate (dorsolateral striatum) affect: Week 1, no dopamine response/signal initially. Week 2, slight increase. Week 3, continued elevation

Question 46

What is happening mentally in terms of compulsive habit formation?

Answer 46

As addiction occurs, person goes from "I want the drug" (rewarding affects) to "I need the drug" (habit formation with less rewarding affects)