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"Absinthe Drinker" Pablo Picasso (1910)

Neurotoxicity AIDS, Cancer NEUROTOXICITY AIDS Mental illness CANCER MENTAL ILLNESS

Homelessness Crime Violence

Health care Productivity Accidents

Between 50% and 80% of Adult Male Arrestees Tested Positive for Illicit Drug Use in 2000
100% 90% 80% 70% 60% 50% 40% 30% 20% 10%

Drug Use Correlates with Crime

Albany Albuquerque Anchorage Atlanta Chicago Cleveland Dallas Denver Detroit Honolulu Indianapolis Miami New Orleans New York Philadelphia Phoenix Portland Sacramento San Antonio San Diego San Jose Seattle Spokane Tuscon
2000 Arrestee Drug Abuse Monitoring: Annual Report, April 2003.

0%

However advances in science have revolutionized our fundamental views of drug abuse and addiction, showing us that: abuse is a preventable behavior addiction is a treatable disease

Common Myths About Drug Abuse

Drug abuse equates to drug addiction Alcohol is not a drug Addiction is a moral weakness You have to hit rock bottom to recover You have to want treatment for it to be successful Drug abuse is more common among minorities

Why Do People Take Drugs in The First Place?

To feel good
To have novel: feelings sensations experiences AND to share them

To feel better
To lessen: anxiety worries fears depression hopelessness

Vulnerability
Why do some people become addicted while others do not?

Biology/genes

Biology/ Environment Interactions

Environment

DA Receptors and the Response to Methylphenidate (MP)

High DA receptor high
Dopamine receptor level

Low DA receptor

low

As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant
Adapted from Volkow et al., Am. J. Psychiatry, 1999.

Como acta la droga para producir adiccin?

Inicalmente las personas consumen drogas esperando un cambio en su estado de nimo, su percepcin o en su estado emocional
Es decir..

esperan cambios en su cerebro

Se sabe que independiente de todas las diferencias que existen entre las distintas drogas, la mayora produce un aumento en la dopamina y la serotonina..

Your Brain on Drugs Today

Front of Brain

Back of Brain

1-2 Min

3-4

5-6

YELLOW shows places in brain where cocaine goes (striatum)

6-7

7-8

8-9

9-10

10-20

20-30

Fowler et al., Synapse, 1989.

GABA and Glutamate Role in Motivation

Basolateral Amygdala

Prefrontal Cortex

Mediodorsal Thalamus

Nucleus Accumbens

Ventral Pallidum

Dopamine
Ventral Tegmental Area

Motor Nuclei

GABA Glutamate
Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.

Circuits Involved In Drug Abuse and Addiction

All of these must be considered in developing strategies to effectively treat addiction

Natural Rewards Elevate Dopamine Levels

FOOD
200

SEX
DA Concentration (% Baseline)
200 150

NAc shell
% of Basal DA Output 150

Copulation Frequency

100 Empty 50 Box Feeding

100

15 10 5 0

0 0 60 120 180
Sample Number 1 2 3
Female Present

Time (min)

Mounts Intromissions Ejaculations

Di Chiara et al., Neuroscience, 1999.

Fiorino and Phillips, J. Neuroscience, 1997.

Effects of Drugs on Dopamine Release

1100 1000 900 800 700 600 500 400 300 200 100 0 Accumbens

AMPHETAMINE
400 % of Basal Release

% of Basal Release

Accumbens

COCAINE
DA DOPAC HVA

DA DOPAC HVA

300 200 100 0

1 2 3 4 Time After Amphetamine

5 hr

2 3 4 Time After Cocaine

5 hr

250 % of Basal Release 200 150 100

% of Basal Release

NICOTINE
Accumbens Caudate

250 200 150 100

Accumbens

MORPHINE
Dose (mg/kg)

0.5 1.0 2.5 10

0
0 1 2 3 hr Time After Nicotine

2 3 4 Time After Morphine

5hr

Di Chiara and Imperato, PNAS, 1988

Dopamine D2 Receptors are Lower in Addiction

Cocaine
DA DA DA DA DA

DA DA

DA DA DA DA DA

Meth

Reward Circuits

Non-Drug Abuser

Alcohol
DA DA

DA DA

DA
DA

Heroin
Control Addicted

Reward Circuits

Drug Abuser

Dopamine Transporters in Methamphetamine Abusers

Motor Task

Dopamine Transporter Bmax/Kd

2.0 1.8 1.6 1.4 1.2 1.07

Loss of dopamine transporters in the meth abusers may result in slowing of motor reactions.

Normal Control

Time Gait (seconds)

9 10 11 12 13

2.0 1.8 1.6 1.4 1.2 1.0 16 14 12 10 8

Memory task Loss of dopamine transporters in the meth abusers may result in memory impairment.

Delayed Recall (words remembered)

Methamphetamine Abuser

Volkow et al., Am. J. Psychiatry, 2001.

CRAVING INDUCTION IN A PET SETTING

5 4 3 2 1 0 -1

DCRAVING

N = 13

Neutral

Cocaine

Conditioned Association

2.5

STIMULI

2.0

1.5

1.0

.5 0

Nature Video

Cocaine Video
Childress et al., Am. J. Psychiatry, 1999

Cocaine Craving:
Population (Cocaine Users, Controls) x Film (cocaine, erotic)

Cingulate
Signal Intensity (AU)

Ant. Cing.

Cocaine Film Cocaine Film

Erotic Film

IFG

Controls Cocaine Users

Garavan et al., Am. J. Psychiatry, 2000.

Drug Addiction: A Complex Behavioral and Neurobiological Disorder

Historical
- Prior experience - Expectation - Learning

Drugs Brain Mechanisms Behavior Environment

Physiological
- Genetics - Circadian rhythms - Disease states - Gender

Environmental
- Social interactions - Stress - Conditioned stimuli

Addiction Changes Brain Circuits

Non-Addicted Brain Addicted Brain
Control

Control

Saliency

Drive

NOT GO

Saliency

Drive GO
Memory

Memory

Source: Adapted from Volkow et al., Neuropharmacology, 2004.

Esto explica porque no se puede salir facilmente

El tratamiento es fundamental

Allostatic Change in Mood State associated with Transition to Drug Addiction

Adapted from: Koob GF and Le Moal M, Neuropsychopharmacology, 2001, 24:97-129.

[C-11]d-threo-methylphenidate

DAT Recovery with prolonged abstinence from methamphetamine

Normal Control

high

Methamphetamine Abuser (1 month detoxification)

low

Methamphetamine Abuser (24 month abstinent)

Volkow et al., J. Neuroscience, 2001.

Se necesita mantener siempre claro los objetivos terapeuticos reales!