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BIOLOGY OF BIOLOGY OF ADDICTION: ADDICTION:
What Neuroscience Has to Tell Us About Addiction as a Brain Disorder
Daniel P Logan, M.D., FACEP, ABAMFlorida Recovery CenterAddiction Medicine, Emergency Medicine Assistant Professor, Dept. of PsychiatryUniversity of Florida College of Medicine
ASAM Definition of ADDICTIONASAM Definition of ADDICTION
“Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations…addiction often involves cycles of relapse and remission”
Four Options to Explain AddictionFour Options to Explain AddictionBrain DisorderMatter of Will- “Disorder of Choice”Bad CharacterSelf Medication
Rectal Cranial Inversion
immoralimmoral
weak
willedweak
willedbadbad
depressed
depressed
irresponsible
irresponsible
Moral Weakness or Stigma ViewMoral Weakness or Stigma View
Why observations make you think Why observations make you think itit’’s not a disease?s not a disease?
Looks like weak willed – they should be able to stop if they put their mind to it
They caused it themselves Your own experience with being able to stop
drugs successfully Consequences of use are immoral, sinful and
bad People should be aware that drugs are bad for
them and should not have used them in the first place
Despite ‘good’ conventional medical, psychiatric and religious care, addicts get worse
It hurts others Prejudice – your negative experience
What observations provide What observations provide evidence that it is a disease?evidence that it is a disease?They seemed liked such normal people
until they started using drugsIt tends to run in familiesNot everyone who uses drugs becomes
addictedThey use compulsively and can’t stop
even with their best efforts Has predictable symptoms – they get
worse with timeReasonable people would stop under
those conditionsSome people like drugs and some don’t
Healthy Heart Diseased Heart
ADDICTION IS A DISEASE OF THE BRAINAs other diseases, it affects tissue function
Control Cocaine Abuser
Decreased Brain Metabolism in Drug Abuse Patient
Sources: From the laboratories of Drs. N. Volkow and H. SchelbertSources: From the laboratories of Drs. N. Volkow and H. Schelbert
High
Low
Nucleus accumbens
AmphetaminesOpiatesTHCPCPKetamineNicotine
Alcohol benzodiazepines barbiturates
Dopamine Pathways
VTA
NTNT Normal FunctionsNormal FunctionsDopamine
(pleasure, learning)
Serotonin (emotional stability)
Norepinephrine (behavioral &
physical activity)
Pleasure (hunger/thirst/sexual), attention, organization of thought, muscle control and motor function
Regulates mood, emotions, thought processes, sleep, and appetite
Energy, motivation, attention span, alertness, pleasure, assertiveness, confidence, heart rate, blood pressure, etc.
Glutamate and GABAGlutamate and GABA
How Drugs of Abuse Effect How Drugs of Abuse Effect DopamineDopamine
Inhibit Reuptake of DopamineStimulate Dopamine transporter
◦Cocaine, Amphetamine, Methamphetamine, XTC
Modulate firing of Dopamine releasing cells by actions on GABA and Glutamate◦Nicotine, alcohol, opiates, cannabis◦Cocaine, Amphetamine, Methamphetamine,
XTC
Drugs, Brains,and Behavior: The Science of Addiction; NIDA, March 2007
Initiation of AddictionInitiation of Addiction
Adolescents◦Risk taking◦Novelty seeking◦Responsive to peer pressure◦Incomplete development of frontal regions
involved in “executive function”
The developing brain……..
What happens when you expose the developing brain to drugs during adolescence??
Gateway Drug
Adolescent Brain ChangesAdolescent Brain ChangesEarlier drinking more likely to result in
alcohol dependence independent of family hx (Grant 1998)
Exposure of alcohol may indeed cause alterations in brain chemistry…. There are studies indicating heaving drinking during adolescence causes memory and neuropsychological changes (Brown, et al)
Alternative explanation that early use may simply be a marker for example high novelty seeking behavior which is associated with early use as well as a risk for alcohol dependence
Adolescent Brain ChangesAdolescent Brain ChangesAnimal studies show that early exposure to
alcohol results in longer term problems such as cognitive and behavioral problems
Stress during adolescence maybe important factor in causing predisposition to etoh – adolescents perception of stress was associated with larger quantities of alcohol consumption
Remodeling of brain during adolescence – especially noted in the dopaminergic setting
GeneticsGeneticsGenes either increase risk or are
protectivePersistent drug use leads to gene
transcription modification-part of neuro-plasticity◦Htrlb receptor gene absence greater attraction
to cocaine and alcohol◦Curl receptor gene presence makes less
responsive to morphine◦ALDH*2 if two copies less likely to develop
alcoholism
GeneticsGenetics
Twin studies in alcoholSway study of sons of alcoholicsIf have one alcoholic parent 3-4 times
increase risk of alcoholism
ALLOSTASISALLOSTASISHomeostasis feedback-Allostasis “feed
forward”State of chronic deviation of regulatory
system from normal i.e. homeostasis“The New Normal”“I don’t even get high anymore”Brain adaptation to persistent drug
exposure- NOT the same as tolerance
ToleranceTolerance
Tolerance- defined by either of the following:
◦ A need for markedly increased amounts of the substance to achieve intoxication or desired effect
◦ markedly diminished effect with continued use of the same amount of the substance
WITHDRAWALWITHDRAWAL
Withdrawal- the predictable constellation of signs and symptoms following the abrupt discontinuation of, or rapid decrease in, the consumption of a drug used consistently for a period of time.
Effects of WithdrawalEffects of Withdrawal
Decrease in Dopamine levels◦Decrease in response to normally rewarding
stimuliIncrease in “stress system” elevated CRF
◦Significant increase in anxiety and dysphoria
CravingCraving
NOT just wanting or liking something◦“I’m craving a Starbucks about now”
A MIDBRAIN (limbic system) process involving both memory and emotion
Similar to hunger and thirstPreviously neutral stimuli take on drug
related significance
The Memory of DrugsThe Memory of Drugs
Nature VideoNature Video Cocaine VideoCocaine Video
FrontFront of Brainof Brain
Back of BrainBack of Brain
AmygdalaAmygdalanot lit upnot lit up AmygdalaAmygdala
activatedactivated
"People, places and things...""People, places and things..."
RELAPSERELAPSERe institution of drug takingPersistence of dysregulation of reward
system◦Length of dysfunction related to drug and
personTriggered by:
◦Drug re exposure- may be other drug of abuse- need not be DOC
◦Emotional state◦Stress
Differing Drug EffectsDiffering Drug Effects
Nicotine appears to have very long lasting and strong persistence of midbrain sensitivity to nicotine re-exposure
Methamphetamine, XTC, bath salts- significant destruction of neurons both midbrain and cortex
RECOVERY IS THE ANSWERRECOVERY IS THE ANSWER
Daniel P Logan, M.D., FACEP, ABAM
Florida Recovery CenterAddiction Medicine, Emergency Medicine Assistant Professor, Dept. of PsychiatryUniversity of Florida College of [email protected]