Lecture 3: psychostimulants

Question 1

what is a stimulant?

Answer 1

Increases alertness and energy, often elevating mood and the appeal of drug-paired events via increase of catecholamine transmission (DA, NE, E)

Question 2

where do stimulants act on? what are their general effects?

Answer 2

block uptake or induce release of catecholamine transporters

Question 3

what are the different types of stimulants, with a few examples?

Answer 3

• Plant based: cocaine, ephedra, Khat leaves
• synthetic: d-Amphetamine, meth-amphetamine, methylphenidate, MDMA, modafinil

Question 4

do stimulants enhance cognition in healthy individuals?

Answer 4

unclear, mostly expectancy/placebo effect

Question 5

effect of Methylphenidate on cognition in healthy people

Answer 5

small improvements in working memory, processing speed and subjective alertness, but increased perseverative and other errors

Question 6

effect of Modafinil on cognition in healthy people

Answer 6

small improvements in working memory and subjective alertness, but induced overconfidence in sleep-deprived youth

Question 7

effect of Caffeine on cognition in healthy people

Answer 7

small improvements in memory and learning

Question 8

what is the severity of development of substance use disorders of stimulants?

Answer 8

moderate to severe with higher rates people with comorbidities (e.g. other SUDs and psychiatric disorders)

varies with substance:
nicotine (most addictive) > cocaine > alcohol > cannabis

Question 9

how long does it take from dependence to remission?

Answer 9

depends on the substance:
nicotine (slowest) > alcohol > cannabis > cocaine (fastest)

Question 10

what are “internalizing” co-morbidity?

Answer 10

Difficulty regulating inwardly directed emotional turmoil.
e.g. Sadness, fear, self-critical perfectionism

Question 11

what are “externalizing” co-mobidities?

Answer 11

Difficulty regulating outwardly directed emotional turmoil.
e.g Impulsivity, irritable, aggression, etc.

Question 12

what are some environmental factors that can lead to internalizing and externalizing?

Answer 12

physical abuse, emotional abuse, emotional neglect, physical neglect, sexual abuse

Question 13

what disorders do “internalizing” and “externalization” lead to?

Answer 13

internalization: major depression, anxiety, panic disorder, animal phobia, situational phobia

externalization: alcohol dependence, other drug dependence, adult antisocial behavior, conduct disorder

Question 14

what are HiTOPs (Hierarchical Taxonomy of Psychopathology)

Answer 14

“Biological parameters linked to higher levels influence a wider range of related behaviors than those linked to lower levels.

Question 15

what are the main models to see “why they can’t stop”?

Answer 15

1. Increased goal-directed approach (conditioned and sensitized incentive salience).
2. Development of compulsions (an inability to disengage from outcome-insensitive habits).
3. Switch from approach (to reward) to avoidance (of stress & withdrawal)

Question 16

how does cue-induced reinstatement change with the amount of time of withdrawal (for cocaine and Heroin) ?

Answer 16

increases with time:
cocaine: increase up to 2 months after, where it plateaus
heroin: all time high at 2 weeks, where it gradually decreases after

Question 17

effect of withdrawal in drug-seeking behavor

Answer 17

does not induce drug seeking, until you learn that taking the drug helps with withdrawal effects

Question 18

what is the effect of giving a DA antagonist of cocaine self-administration?

Answer 18

• breakpoint is lower (decreases willingness to give effort for the drug)
• injection rate is higher
• Drug-induced reinstatement prevented by DA antagonists
  (cue- and stress-induced reinstatement is decreased)

Question 19

role of the ventral and the dorsal striatum in withdrawal

Answer 19

ventral: linked to reward-seeking behavior
dorsal: linked to habit-like behaviors (willing to go through withdrawal symptoms if it means that they will get a drug afterwards)

Question 20

where in the brain do we see dopamine response with cocaine, amphetamine, and ethanol?

Answer 20

all in the ventral striatum

Question 21

what is the effect of autoreceptors on impulsivity?

Answer 21

the lower the level of auto-receptors, the higher the dopamine release, the higher the impulsivity seen, so dopamine is linked to impulsivity

Question 22

what is the effect of dopamine on pleasure?

Answer 22

it has no effect

Question 23

what is the effect of dopamine on incentive salience/reward seeking?

Answer 23

dopamine is required for incentive salience/reward seeking, depleting dopamine results in drug use (except in cigarette use)

Question 24

why are pharmacotherapies for SUD targeting DA not enough?

Answer 24

does have an effect on reward seeking but no DA effect on pleasure or use of easily available drug (will not seek it but if it is there, they will take it)

Question 25

repeated amphetamine administration causes ________

Answer 25

dopamine sensitization

Question 26

with cocaine, there is a ____________ induced striatal DA release

Answer 26

drug cue-induced

Question 27

DA release co-varies with _______ (with cocaine)

Answer 27

craving

Question 28

low DA autoreceptors (low midbrain DRD2) = what?

Answer 28

High drug cue-induced craving + high DA release

Question 29

striatal DA release can be caused by :

Answer 29

stress, drug cues, cravings

Question 30

what is the effect of naloxone-induced withdrawal?

Answer 30

DA release in the dorsal striatum in people with opioid use disorder

Question 31

what are 4 relapse triggers and what do they cause?

Answer 31

they induce DA release:
low dose of the drug
drug-paired cues
stress
withdrawal

Question 32

what is the DA response when a drug is expected in healthy controls vs in cocaine use disorder?

Answer 32

DA higher in healthy when you expect drug vs placebo, and lower in SUD when expecting drug vs placebo

Question 33

A greater propensity to high dopamine states might ______ risk for
SUDs and associated problems.

Answer 33

increase

Question 34

what is the three-factor diathesis-stress model?

Answer 34

a model to predict early onset DSM-5 disorder looking at midbrain DA autoreceptors, externalizing personality traits, and early life adversity

interview at about 18 years old then follow up 2 to 3 years later

Question 35

what is the mediation analysis?

Answer 35

looking at the effect of childhood trauma and brain response interactions on psychiatric disorder.

Question 36

is there really a contradiction between PET and fMRI data?

Answer 36

PET data suggest low DA cell inhibition.
fMRI data suggest low brain activations

fMRI BOLD signal reflects confluence of multiple transmitters, BUT Dopamine pathway-related psychiatric disorders can show increased and decreased activity depending on the environmental conditions; e.g., presence vs absence of disease relevant cues

Question 37

Model with Alcohol v Juice Cues Predicts __________________ via the binomial logistic regression

Answer 37

Problem Drinking 7 Years Later

Question 38

Young adults at risk for substance use disorders (SUDs) exhibit altered _____________ dopamine.

Answer 38

mesocorticolimbic (MCL)

Question 39

which model provided better sensitivity and specificity?

Answer 39

the PET data (small sample)

Question 40

the combination of what 3 things predicts a wide range of commonly comorbid mental health problem?

Answer 40

(i) altered MCL pathway regulation (as early as age 14), (ii) high early life adversity, and (iii) high EXT behaviors (poor mood and impulse regulation)

Question 41

what are some treatment options for psychostimulant drug addiction?

Answer 41

Contingency Management Therapy*
Motivational therapy / CBT
TSF (Twelve step facilitation)

Methylphenidate
Modafinil
SSRIs
Ketamine
DBS (Deep Brain Stim)
N-acetyl-cysteine
TMS (Transcranial Magnetic Stimulation)
OSU6162
Psychedelics