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Chapter 9: Drug Abuse and Addiction - Coggle Diagram
Chapter 9: Drug Abuse and Addiction
Schedule of Controlled Substances
Schedule 1: Substances that have NO ACCEPTED MEDICAL USE, have high abuse potential
ex. Heroin, LSD, mescaline, marijuana, THC, MDMA, psilocybin
MDMA in phase 3 trials for PTSD
THC legalized in 33 states
psilocybin: major effects in depression from cancer diagnosis
LSD: effective in clinical depression
Substance 2: have a high abuse potential with severe PSYCHIC/PHYSICAL dependence liability
ex. opium, morphine, cocaine, amphetamine, oxycodone, fentanyl
Schedule 3: have an abuse potential lower than schedules 1 and 2, including quantities with limited quantities of narcotics and nonnarcotics
barbiturates
Schedule 4: lower abuse potential than schedule 3
Schedule 5: have lower abuse potential than schedule 4, containing limited amounts of certain narcotics for antitussive (cough suppressant) and antidiarrheal purposes
Drug Abuse and Addiction
Addiction potential of a substance: influenced by its route of administration
PO: relatively SLOW absorption of the drug
IV, inhalation/smoking: RAPID drug entry into brain and FAST ONSET of drug action
"Soldier's disease": inject themselves with morphine through hypodermic needle
3 Categories of harm/Criteria to assess harmfulness
physical harm to the individual user caused by the drug
long-term health effects
HIV, hepatitis, infection
lung cancer
impaired brain function
ability to perform cognitive or motor tasks
lethality
how common is overdose --> margin of safety
tendency of the drug to induce dependence
dependence liability
how likely is the user to become addicted (CAPTURE RATIO)
tobacco: 33%, heroin: 23%, cocaine: 17%, alcohol:15%
effect of drug use on families, communities, and society
harm to family and community
domestic violence, theft, medical costs
Most abused drugs are POSITIVE REINFORCERS
consuming drug STRENGTHENS whatever PRECEDING behavior was performed
Substances that are strong reinforcers when taken IV/inhaled have STRONG ABUSE POTENTIAL
Drug reward: the positive experience associated with the drug (i.e. the "high")
Craving: strong URGE to take the drug
Some drugs lead to PHYSICAL DEPENDENCE
attempts at abstinence lead to WITHDRAWAL
motivates user to take the drug again
negative reinforcement: alleviation of withdrawal symptoms
leads to a continuous loop of repeated attempts at abstinence followed by relapses
Transition to Addiction in Humans
Why don't the negative aspects of drug addiction counteract the positive reinforcement of drug use
drug-induced euphoria occurs VERY QUICKLY after consumption
negative consequences occur LATER and are usually linked to a LONG PATTERN OF USE
Koob and Le Moal Model
drug taking behavior: an "impulsive" stage to a "compulsive stage"
impulsive stage
primary motivation: substance's positive reinforcing effects
goal-oriented reward
compulsive stage
primary motivation: negative reinforcement (relief from drug withdrawal)
behavior is habit-like
Conditioned withdrawal
withdrawal symptoms may be clasically conditioned if they repeatedly occur in the SAME ENVIRONMENT
The Disease Model
Addiction: "a chronically relapsing disorder" characterized by compulsion to seek and take the drug, loss of control in limiting intake, emergence of a negative emotional state when access to the drug is prevented
Addiction is tied to changes in brain structure and function
Medicalization of drug addiction
Major impact on societal perceptions on addiction
earlier views emphasized personal and moral weakness (moral model)
reduces the sense of guilt in recovering addicts
chronic, relapsing: drug-free periods (remissions) are often followed by relapses
Alcoholism: declared a disease in 1950s
DSM-5: "Substance use disorder"
individual has manifested a MALADAPTIVE pattern of substance use for at least 12 months --> significant impairment/distress
covers 10 classes of drugs (all activate reward circuitry)
at least 2/11 additional criteria must be met
severity component: mild, moderate, severe
Criticisms of the Disease Model
no lab tests can identify the cause
addiction may not be chronic -- drug may not be outside of the control of the user (i.e. heroin use in Vietnam vs. return home)
addicts use drugs in the absence of other positive reinforcers
brain-centric view does not take into account the whole person
lack of personal responsibility - "the disease made me do it"
Disease or not a disease: does it matter?
reduces guilt and helps deal with relapse
insurance companies
Rat Park
designed to contrast oral morphine self-admin of isolated rats vs. social rats (from social "rat parks"
isolated rats increased their consumption
social rats decreased their consumption
showed that housing conditions appear to play an important role in determining morphine self-admin
Animal Models of Drug Abuse and Addiction
Studying drug reward
CPP (conditioned place preference)
Intracranial self-stimulation (ICSS)
threshold for REWARDING self-stimulation is REDUCED when animals are treated ACUTELY with drugs
brain reward circuitry is more sensitive
During withdrawal from CHRONIC treatment: same drug cause an INCREASE in threshold value
reward circuit is damaged
Self-administration (dose manipulation)
fixed-ratio schedule: dose-response function is an inverted U-shaped curve
At HIGHER doses, number of reinforcers (i.e. # of drug deliveries) DECLINES
due to satiation, aversive reactions, behaviorally disruptive side effects (i.e. passing out)
Breaking point: Animals initially trained in continued reinforcement schedule --> switched to FR
FR schedule is INCREASED PROGRESSIVELY until the animals stop responding
response ratio at which responding stops: BREAKING POINT
breaking point generally increases with higher doses
Relapse
FORCE abstinence
REINTRODUCE stimuli known to provoke renewed responding
priming: give a little bit of drug
stress: stressful situation causes them to relapse and hit lever
environmental cues previously paired with drug delivery
Neurobiology of addiction
DA and Reward
Reward circuit = mesolimbic DA pathway (VTA to NAcc)
central role in acute rewarding and reinforcing effects of abused drugs
essential for drug reward for SOME drugs (psychomotor stimulants) but NOT ALL drugs (heroin, alcohol)
DA may act as:
"pleasure transmitter" (emotional/affect)
encode pleasure during drug use
ex. partial DA agonist turned patients to compulsive gamblers and sex addicts
EVIDENCE AGAINST DA AS PLEASURE TRANSMITTER
Release of DA in the NAcc produces feelings of pleasure (euphoria or "high")
cocaine users depleted of catecholamines experience NO decrease in euphoria
pleasure aspects are relatively unaffected by DA manipulation
mediator of incentive salience (motivation)
wanting vs. liking
Incentive salience model: Addiction occurs after a shift from "liking" (euphoria) the effects of a drug to "wanting" (craving) the effects of a drug
as addiction develops, user experiences an increase in "wanting" the drug (sensitization)
NO CHANGE/SLIGHT DECREASE in drug liking
A REDUCTION in cocaine craving was found after catecholamine depletion (no effect on cocaine-induced euphoria)
Acute phenylalanine-tyrosine depletion (to lower DA levels) significantly decreased cocaine and concaine-induced craving
reward prediction signal (cognitive)
acts as a reward-prediction error signal when the animal is expecting a reward
DA firing signals the DIFFERENCE between PREDICTION and ACTUAL OCCURENCE of rewards
events that are BETTER THAN EXPECTED: DA neurons fire
more repeated behaviors
events that occur AS EXPECTED: no change in firing (still provides reward)
behavior is unchanged, learned nothing
events that are WORSE than predicted: neurons are inhibited
behaviors are not repeated
Neuroadaptations: repeated exposure to drug --> long-term changes in brain --> development of addiction
Two types of neuroadaptations involved in the transition to addiction
within-system adaptations in the reward circuit: progressive down-regulation of activity
Between-system adaptations: gradual recruitment of the anti-reward system
effects of drugs are automatically counteracted by opposing actions in the body to maintain homeostasis
anti-reward system is activated during WITHDRAWAL
shift from impulsive --> compulsive
activate CRF in amygdala (physiological withdrawal symptoms)
UP-REGULATION OF ANTI-REWARD SYSTEM
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Drug Abuse and gene expression
^FosB: transcription factor
rapidly induced in the NAcc and the dorsal striatum and accumulates in the NAcc for weeks
mice overexpressing ^FosB --> enhanced sensitivity to a variety of drug effects
modulates gene expression by epigenetics mechanisms: promote or repress transcription
early life stress leads to epigenetic changes --> increased risk for substance abuse disorders
Brain
reduced striatal D2 receptor levels in addicts
underlies lack of impulse control and planning, poor emotional regulation, increased drug salience
structural functional abnormalities in the PFC in addicts
executive function: planning, organization, problem solving, mental flexibility, valuation of incentives