Substance Use Disorders Flashcards
Tolerance
Progressively diminished physiological response to a drug with repeated drug exposure
o A rightward shift in the dose-effect function.
Sensitization
Progressively augmented physiological response to a drug with repeated drug exposure,
o A leftward shift in the dose-effect function.
Dependence
A physiological state induced by repeated exposure to a drug, in which presence of the drug is required for the system to function normally.
o Removal of the drug often precipitates a withdrawal syndrome.
Craving
A subjective state of intense desire for a particular goal, such as for a drug of abuse.
o Based in subjective experience
o A state of increased motivation to obtain a particular goal, or a narrowing of focus such that one goal is pursued at the expense of others.
Addiction
Includes the following concepts:
o Loss of control over limiting drug intake
o Drug-taking persists despite negative consequences
o A narrowing of the motivational/emotional repertoire such that alternatives to drug-seeking (work, relationships, leisure activities) are no longer pursued
o The potential for relapse throughout the life span, regardless of successful treatment interventions or long periods of drug abstinence.
Reinforcement
The process by which the outcome of a behavior increases the likelihood that the behavior will be repeated.
o Can be positive or negative
Reward
Often defined as the subjective emotional experience (pleasure, euphoria) that can accompany positive reinforcement.
Impulsive Behavior
Two features
1) Tendency to consistently choose immediate reinforcement over delayed gratification, even when the immediate reinforcement is smaller or less beneficial
2) Impairment in the ability to inhibit a course of action once initiated.
o Results from impaired PFC inhibitory control
Compulsive Behavior
Perseveration in a certain behavioral strategy even in the face of unsuccessful or adverse outcomes.
o Result from shift from prefrontal-accumbens motor circuits → dorsal striatal control (dorsal striatum mediates habits)
Describe the role of the dopaminergic system in the nucleus accumbens and related areas in reward and reinforcement.
Drugs of abuse = elevate DA levels in nucleus accumbens → promotes cellular learning mechanisms
o Contributes to neural coding of reward (motivation)
o Stimulate DA region → reward response
o Block DA receptors → blunts reward
So:
• DA for “wanting” (identifying relevant reinforcers and pursuing them)
• Opioids for “liking” (subjective emotional experience of pleasure upon interacting with reinforcer)
DA in substantia nigra and ventral tegmental area (VTA)
• Ascending DA pathways → striatum (includes nucleus accumbens)
o Main cell type in striatum = medium-spiny neuron
• Spiny dendrites = massive capacity to receive and integrate info
o Output = integrates complex, neurochemically specific inputs
• Glutamate input
• DA input
Reward error prediction hypothesis
Electrophysiological firing of DA neurons occurs:
• First time organism experiences new primary reward
• When observing stimuli that reliably predict expected reward
• When previously experienced reward is better than predicted
Describe the neuroanatomy of appetitive behavior, specifically the cortico-striato-
pallidal-thalamic (CSPT) loop.
o Cortico: includes PFC, amygdala, hippocampus
o Striato: nucleus accumbens
o Pallido: ventral pallidum
o Thalamic: MD thalamus → cortical motor-planning regions
Explain how reward, withdrawal, learning and impulse control may play a role in the development of addiction.
Reward-based theories of addiction (anhedonia hypothesis)
o Most drugs = positive reinforcers (are “wanted” and “liked”)
o Most drugs = enhance rewarding electrical brain stimulation
o Opiate drugs and DA drugs = enhance brain stimulation & reward
Withdrawal-based theories
o Drug dependence becomes homeostatic adaptation
o Leads to tolerance
o Without drug = withdrawal (physical and psychological)
o Cycle fueled by attempt to “self-medicate” = alleviate withdrawal
Learning-based theories
o Addiction = chronic, relapsing
o Incentive-sensitization hypothesis: drug use → long-lasting sensitization of DA’s ability to produce “wanting”
o Reward-error prediction hypothesis: enhanced DA release with drug → condition in which all stimuli encountered during use are experienced as “better than expected”
Role of impulsive behavior:
o Tendency to choose immediate reinforcement over delayed gratification (even if less beneficial)
o Impaired ability to inhibit course of action once initiated
o Result: excessive “wanting” of drug so overwhelms inhibitory control mechanisms
Role of compulsive behavior:
o Preservation in behavioral strategy even in face of adverse outcomes
o Result: “wanting” drug even though they “like” it less or have adverse outcomes
Describe the three stages of addiction
Binge/intoxication
o Acute euphorigenic properties = critical
o DA release promotes cellular learning and memory
Withdrawal/negative affect
o Alleviate physical/emotional symptoms with drug-seeking behavior
Anticipation/preoccupation
o Overlearned drug cues promote relapse
o Frontal deficits promote impulsive and compulsive behavior
o Lasts over lifespan
Symptoms of alcohol intoxication
Low levels:
- pleasant, sometimes euphoric state
- diminished coordination
- impaired judgement
Severe levels:
- aggression
- poor judgement
- somnolence
- severe decrease in coordination
- slurring of words
- loss of gag reflex
- apnea
Symptoms of opioid intoxication
Low levels:
-euphoria followed by somnolence, miosis
Severe levels:
- somnolence
- apnea
- death
Symptoms of cocaine/psychostimulant intoxication
Low levels:
- euphoria
- inaomnia
- intense concentration
- loss of appetite
Severe levels:
- anxiety
- psychosis
- agitation
- seizures
- cardiac/cerebral ischemia
Symptoms of hallucinogen intoxication
Low levels:
-intense change in perceptual state leading to unusual visual, auditory, and other sensory experiences
Severe levels:
-intense, more hallucinatory state bordering on psychosis with impulsive acts related to perceptions
Symptoms of alcohol withdrawal
Common symptoms:
- anxiety
- nausea
- tremors
- sweating
- sleeplessness, restlessness
- headaches
- rapid pulse and high BP
Dangerous symptoms:
- Psychosis
- Delirium
- Seizures
Timeline:
-Common symptoms usually subside in 72-96 hours; DT can last 10+ days
Symptoms of benzodiazepine withdrawal
Common symptoms:
- anxiety
- nausea
- tremors
- sweating
- sleeplessness, restlessness
- headaches
- rapid pulse and high BP
Dangerous symptoms:
-seizures
Timeline:
-dependent on half-life of drug and its metabolites (days to weeks)
Symptoms of opioid withdrawal
Common symptoms:
- nausea
- vomiting
- craving
- rhinorrhea
- diarrhea
- tearing
- muscle aches and cramps
- gooseflesh
- dilated pupils
Dangerous symptoms:
- dehydration from diarrhea and vomiting
- leaving care to get more drug
Timeline:
-dependent on half-life of drug and its metabolites (varies from day: heroin/morphine to weeks: methadone)
Symptoms of cocaine/psychostimulant withdrawal
Common symptoms:
- tired
- prolonged sleeping
- amotivational
- depressed
- overeating
- craving
Dangerous symptoms:
-will leave to get more drug
Timeline:
-cocaine is shorter than methamphetamine, which has longer 1/2 life
Alcohol use disorder: epidemiology
o 8.7% population diagnosed with substance use disorder
o Most started in adolescence
o Trends: decrease in cigarettes and cocaine, no change in alcohol, increase in marijuana, ecstasy, and prescription painkillers
o Majority of drug users remain in control of use
Alcohol use disorder: pathophysiology
Genetics:
• Heritability of 55-60% for alcohol use disorder
• Inheritance of impulsivity (low levels of serotonin)
Environmental factors:
• Community where substance use is accepted
• Parental use
• Earlier the use begins = more likely to have loss of control
Defense mechanisms
• Denial
• Rationalization
Biological = Dopamine and reward
Alcohol use disorder: prognosis
o Relapse = frequent, frustrating, and expectable
o 1st months to year = most relapse-prone time
o Increased risk: stress, anger, exposure to drugs or drug cues
Treatment for alcohol withdrawal syndrome
o Most common = Benzodiazepine taper: offset unopposed opponent process of decreased GABA/increased glutamate function
o Anticonvulsants: offset unopposed state by modulating glutamate function
Psychosocial treatment:
Relapse prevention/CBT
• Avoid stimuli/triggers
• Deal with anger and other negative affective states
• Choose “positive” over “negative habits”
3 main types: • Relapse prevention • Motivational enhancement • 12-step facilitation Each = 80% reduction in drinking days after 1 year
Pharmacologic treatment
Treatment for benzodiazepine withdrawal syndrome
- most common = switch to long-acting benzodiazepine and taper
- some now use anticonvulsants
Treatment for opioid withdrawal syndrome
- can use buprenorphine or methadone with special license
- can use clonidine/benzodiazepine regimen
- intense psychosocial support
Treatment for stimulant withdrawal syndrome
- support
- get into treatment for abstinence as soon as possible
Naltrexone
Blocks effects of endogenous opioids released with alcohol use and cravings
• Interferes with positive reinforcement
• Result: “slips” less likely to lead to full-relapse, less frequent and intense cravings
Acamprosate
- Modulates glutamate system
* Lessens relapses related to negative affect
Disulfiram
- Antagonizes aldehyde dehydrogenase → toxic build-up of aldehyde
- Result: noxious, painful, frightening state → decreased alcohol intake
- Toxic: cardiorespiratory collapse and death
