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 Medicinedlogan@ufl.edu352.265.5549