Addiction Flashcards
What is addiction? (Criteria and definition)
- 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)
What factors influence susceptibility for addiction?
Both genetic and environmental factors influence susceptibility
What is addiction best understood as?
- Best understood as a clinical brain disorder with observable physiological manifestations that underlie pathological aspects of behavior
What are the four stages of drug addiction?
- Use
- Heavy Use
- Early dependence
- Late dependence/Neuroadaptation
How is addiction related to positive/negative reinforcement?
As use disorder progresses, negative reinforcement increases while positive reinforcement decreases
What is the cycle of addiction?
- 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)
What is the definition of substance use disorder according to the DSM-5?
“Substance use disorder descrbes a problematic pattern of using alcohol or another substance that results in impairment in daily life or noticeable distress”
How many symptoms do you need for mild, moderate, and severe SUD (according to DSM-5)
- 2-3 symptoms: mild
- 4-5 symptoms: moderate
- 6+: severe
How many total symptoms are there for SUD in the DSM and what are they categorized under?
- Physical dependence
- loss of control
- clinical impairment
What are the physical dependence symptoms of SUDs?
- “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)
Loss of control symptoms
- 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
Clinical impairment symptoms
- 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
SUD Manifestations Ilicit
- Narcotics
- Hallucinogens
- Stimulants
- Cannabis (in most states)
SUD manifestations licit
- Cigarettes
- Alcohol
- Cannabis (legal in over 20+ states and DC)
Manifestations- nonchemical
- Gambling disorder (in DSM5)
- Internet gaming disorder (possible)
- Food, porn, sex, shopping, exercise (under study)
What age group misuses alcohol the most?
Ages 26+, probably because they can legally (66.5%)
What age group misuses weed the most?
12-17 year olds have highest prevalence
What are the main effects with alcohol use disorder?
- Loss of control over alcohol drinking
- Negative emotions when not drinking
- Have to drink more for the same effects
Alcohol use deciles (per week)
- 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
What are the risk factors for alcohol use disorder?
- environment
- genetic predisposition
- early traumatic exposure
What are other risk factors for SUDs?
- Men»_space; women
- Adolescents»_space; adults
- Co-morbidity with other psychiatric illnesses
- Pain disorders and other somatic diseases
Enviornmental risk factors: What does exposure to adverse events during early-life and adolescence increase the risks of?
- affective disorders
- increased risk of alc and substance use disorder
What is an important concept about drugs?
- Drugs are chemical ligands that interact with brain neurotransmitter systems and that can change the way people feel by altering neural signaling
Drugs as a stimulus
- 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
What is dopamine?
- A NT released during a happy event or in the presence of a rewarding stimulus
- Both rewarding and reinforcing
What are the two dopamine pathways?
- Substantia nigra to caudate; motor
- VTA to nucleus accumbens; mesolimbic system
Mesolimbic dopamine system: VTA
- 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
Mesolimbic dopamine system: Nucleus Accumbens (NAc)
- amplifies the response to pleasure, amplifying rewarding as a result of the dopamine flowing there
- involved in stress processing, affect/emotion driven
At the synapse (between VTA and NAc)
- 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
What neuroadaptations occur after frequent drug use?
- PET imaging shows decreased dopamine D2 receptors in addicts (downregulated)
- This is beyond the effect of just the release of NTs
How we figure out dopamine was important in SUDs?
- 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
SHAM lesion as control: same surgery but saline or artificial CSF injected
Is addiction learning?
- 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.
Addiction as learning from a society perspective
- 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
Drug paired cues
- 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
basal ganglia function in SUD
learning and memory
Extended amygdala SUD function
reward and motivation, includes the NAc (which sits at the intersection of the basal ganglia and extended amygdala circuit)
PFC area SUD function
control over behavior
What is the larger story of the brain involvement w SUDs, beyond the mesolimbic dopamine pathway?
- 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
Drug paired cues study
- 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
Instrumental learning and drugs
- because drugs are rewards, they support instrumental learning
- actions associated w drug intake are reinforced, occurring with increasingly higher probability
Instrumental learning study
- 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
Tolerance/non-associative learning
- 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
Non-associative learning study
- 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
What causes compulsive habit formation?
- 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
What is happening neurologically during compulsive habit formation? Research study
- 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
What is happening mentally in terms of compulsive habit formation?
As addiction occurs, person goes from “I want the drug” (rewarding affects) to “I need the drug” (habit formation with less rewarding affects)
