Developmental Disease

First Marijuana Use, (Percent of Initiates)

1.5%
67%
5.5%
<12
12-17
18-25
>25
Addiction is a Developmental Disease: It Starts Early
26%

Basic Science Tells Us that Adolescents’Brains Are Still Developing…

Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179
MRI Scans of Healthy Children and Teens Over Time


When Reading Emotion…Adults Rely More on the Frontal CortexWhile Teens Rely More on the Amygdala Source: Deborah Yurgelon-Todd 2000.


Do Adolescents React Differently than Adults to Substances of Abuse?


Rats Exposed to Nicotine in AdolescenceSelf-Administer More Nicotine Than Rats First Exposed as Adults
Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes v19.2

Do We Need Fundamentally Different Strategies At Different Stages of Adolescence?

Americans’ Views of the Seriousnessof Health Problems(Top 10 of 36 Problems) 65%
65%
68%
69%
71%
73%
74%
75%
78%
82%
Stress
Alcohol abuse
Smoking
Child abuse
Violence
HIV/AIDS
Heart disease
Drunk driving
Cancer
Drug abuse
% saying “very serious problem” Harvard School of Public Health/Robert Wood Johnson Foundation/ICR, August 2000
Drug abuse
Smoking
HIV/AIDS
Child abuse
Violence
Stress
Cancer
Drunk driving
Heart disease
Alcohol abuse

Definitions

Drug UseTaking a psychoactive substance for non-medical purposes, out of curiosityDrug AbuseDrug use that leads to problems (e.g. loss of effectiveness in society; behavioral psychopathology, criminal acts)Drug DependenceA maladaptive pattern of drug use leading to clinically-significant impairment or distress, associated with difficulty in controlling drug-taking behavior, withdrawal, and toleranceThe state of needing a drug to function within ‘normal limits’

Nature of Addiction - a continuum of use?

However, addiction is more than mere drug use… Loss of control 

DSM-IV Criteria for Substance Dependence

Tolerance Withdrawal Substance taken in larger amounts or over a longer period than intended Persistent desire or unsuccessful efforts to cut down or control substance use Great deal of time spent in activities necessary to obtain substance, use substance (e.g., chain smoking), or recover from effects Important social, occupational, or recreational activities given up or reduced because of substance use Substance use continued despite knowledge of persistent or recurrent physical or psychological problem likely to have been caused or exacerbated by substance
A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12 month period:

Addiction Involves Multiple Factors

Homelessness Crime Violence
Neurotoxicity AIDS, Cancer Mental illness
Health care Productivity Accidents

Physical vs. Psychological Dependence

Physical DependenceWithdrawal symptoms in the absence of the drugTolerance to its effects with repeated usePsychological Dependence “a relatively extreme, pathological state in which obtaining, taking, and recovering from a drug represents a loss of behavioral control over drug taking which occurs at the expense of most other activities and despite adverse consequences” (Altman et al)“a situation where drug procurement and administration appear to govern the organism’s behavior, and where the drug seems to dominate the organism’s motivational hierarchy” (Bozarth)


Physical Dependence or Withdrawal Model(Negative Reinforcement)
Some drugs produce physical dependence and withdrawal symptoms upon cessation of drug-taking.Withdrawal symptoms are produced by the body in order to compensate for the unusual effects of the drug.Withdrawal symptoms are generally the opposite of the effect produced by the drug.Addicts continue to use drugs in order to avoid withdrawal.Over time, drugs no longer have the same rewarding effects - they merely allow the person to feel “normal.”

Positive Incentive (Hedonic) Models(Positive Reinforcement)

Drugs produce pleasure - a “high.”Some drugs provide indirect positive incentive - they disinhibit behavior that is normally suppressed (e.g., alcohol and social skills).Most drugs of abuse stimulate the brain’s reward circuits.All known drugs of abuse stimulate release of DA/opioids in the nucleus accumbensAnimals will work to micro-inject drugs of abuse and electrically stimulate the same parts of the brainNormal rewards (food, drink, sex) also stimulate DA release

Drug Dependence Among Ever-Users

0
10
20
30
40
Marihuana
Stimulants
Alcohol
Cocaine
Heroin
Tobacco
% Dependent

Why do Mental Illnesses and Substance Abuse Co-occur?

Self-medication hypothesis substance abuse begins as a means to alleviate symptoms of mental illness Causal effects of substance abuse Substance abuse may increase vulnerability to mental illness Common or correlated causes the life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap

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

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

Drive
Saliency
Memory
Control
Non-Addicted Brain
NO GO
Addicted Brain
Drive
Memory
Control
GO
Saliency
Why Can’t Addicts Just Quit? Because Addiction Changes Brain Circuits

Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry

Pharmacological (medications)
We Need to Treat the Whole Person!
In Social Context
Behavioral Therapies
Medical and Social Services


But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma
McLellan et al., JAMA, 2000.

We Need to Keep Our Eye on the Real Target

Abstinence
Functionality in Family, Work and Community
In Treating Addiction…

Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways

Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease

Dopamine Pathways

Functions reward (motivation) pleasure,euphoria motor function (fine tuning) compulsion perserveration decision making
Serotonin Pathways
Functions mood memory processing sleep cognition
nucleus accumbens
hippocampus
striatum
frontal cortex
substantia nigra/VTA
raphe

Drug Disorder

Cocaine and Methamphetamine
Schizophrenia, paranoia, anhedonia, compulsive behavior
Stimulants
Anxiety, panic attacks, mania and sleep disorders
LSD, Ecstasy & psychedelics
Delusions and hallucinations
Alcohol, sedatives, sleepaids & narcotics
Depression and mood disturbances
PCP & Ketamine
Antisocial behavior

Targets of Medication

Methadone, LAAM and Buprenorphine
Activate opioid receptors
Nicotine gum/patch
Activate nicotinic receptors
Naloxone
Block opioid receptors