Adolescents and Substance Abuse Dr. Cynthia Kuhn Department of Pharmacology and Cancer Biology Duke University Medical Center

Drug Use Begins in Adolescence Percent Using in Past Month Alcohol Cigarettes Marijuana Hallucinogens Prescription Rx Age in Years National Household Survey on Drug Use and Health 2008

Tobacco Use is Maximal in Adolescence

Addictive Drug Use Peaks during Adolescence

Alcohol Use Peaks during Late Adolescence

The earlier people start drugs, the more likely they are to develop abuse

Adolescence: What is Going On? Social development: importance of peers Hormonal development Sex hormones Stress hormones Brain development

Adolescent Brain is Still Changing

Phases of Brain Development Infancy: Growth Childhood: Connectivity Adolescence: Pruning

What Functions are Changing? Response to Reward Response to Punishment Neural Circuits that Plan Ahead

Triad of Motivated Behavior Executive Function Reward Avoidance

Reward Areas Develop Before “Thinking” Areas Sommerville and Casey, Curr. Opinion Neurobiol 20:236 (2010)

Adolescents Don’t Like to Wait for Reward Adapted from Psychological Science 5:33 (1994)

Adolescents are Less Sensitive to Aversive Experiences (Punishment!) Adolescent rats do not avoid taste associated with unpleasant experience (nausea)

Reward is More Effective than Punishment in Adolescence Adult

Adolescents Don’t Change Losing Strategies Cauffman et al, Develop. Psychology 46:193 (2010)

Adolescents Do Not Avoid Bad Outcomes

Adolescents are Impulsive

The Yin/Yang of Adolescent Decision Making Helpful Still fine tuning connections- primed to learn Impulsive – try something “just because” Risk taking – will try new things without assurance of success Aren’t inhibited by low probability of success Not helpful Final connections for good decision making are not done Risk taking- will try new things just because they are new Long-term outcome less important Bad outcome less important

What is Different about Addiction Mechanisms in Adolescent Brains? Respond more to rewards Respond less to punishment -different processing of negative emotions Risk taking and Novelty seeking Highs are higher Lows are not as Low

So Is the Brain Primed for Addiction in Adolescence?

Addiction Is a Process of Brain Adaptation Drug use: Reward ADDICTION Withdrawal, Craving Reward circuit Adapts Need drug to Feel Good at all

Addiction is NOT just Dopamine Components of Addiction Rewarding effects of the drugs – dopamine Tolerance and dependence- withdrawal Impaired priority setting/decision making – craving, compulsive use

Neural Basis of Addiction Dopamine

All Addictive Drugs Activate This Circuit DA Cocaine Alcohol Heroin Nicotine

All Addictive Drugs Increase Dopamine Levels

Addiction Is a Process of Brain Adaptation Drug use: Reward ADDICTION Withdrawal, Craving Reward Circuit Adapts Need Drug to Feel Good at all

Reward System Adaptations in Addiction DA Target Neuron DA Receptors Constant DA Release Dopamine Neuron

Dopamine Receptors Are Decreased in Addicts

Addictive Drugs Cause Long Lasting Changes in the Brain Kalivas and Volkow, Arch Gen Psy. 162: 1403

Addiction Is a Process of Brain Adaptation Drug use: Reward ADDICTION Withdrawal, Craving Reward Circuit Adapts Need Drug to Feel Good at all

Executive Function Changes in Addiction: Drugs Become Priority Increased impulsivity: Do things without considering the outcome Impaired memory- Can’t keep things in mind while considering a decision Difficulty shifting priorities Risky decision making Berridge et al, Phil Trans. R. Soc B. 363:3257 (2008)

Addicts Can’t Change Losing Strategies B Win Big, Lose Overall C D Win Small, Win Overall . J. Math. Psychol 54:28 (2010)

Addiction Is a Process of Brain Adaptation Drug use: Reward ADDICTION Withdrawal, Craving Reward Circuit Adapts Need Drug to Feel Good at all

Craving and Misery of Withdrawal: From Activation of Stress Axis Chronic drug exposure triggers stress axis Involves stress peptide CRF Amygdala sends messages to cortex – motivates more drug taking Chronic Addictive Drugs Activate the Stress Axis in the Brain

Summary: Key Processes in Addiction Rewarding effects of drugs Adaptation to drugs – brain biochemistry and structure changes Disturbed decision making Craving associated with Withdrawal – activation of stress axis

What is Different in Adolescent Response to Addictive Drugs?

Cocaine Increases Dopamine More in Adolescents Walker and Kuhn, Neurotox & Teratol 30: 412 (2008)

Adolescents Avoid Drugs that are Aversive Less than Adults

More Lasting Gene Changes after Nicotine Exposure during Adolescence Doura et al, Neuroscience in press, 2010

Summary of Addiction Vulnerabilities in Adolescents Risk taking: more likely to use drugs Less likely to inhibit behavior (refuse when offered) Balance of drug effects different: biased toward pleasant effects Biochemical changes in brain may be more long-lasting

Not Every Adolescent is Equally at Risk

Model of Adolescent Drug Use Genes Brain Development Environment Adolescent Substance Abuse

Temperament + Environment Influence Drug Involvement Alcohol abuse from Age 12 to 18

Does This Mean that Behavior Changes is Impossible? NO

Who can Influence Adolescents? Peers (of course) Parents: especially if they practice what they preach Trusted adults (YOU!)

What Influences Increase or Decrease Drug Involvement Parents using at home No parent limit setting Poor school involvement Deviant peers Decrease Life Satisfaction Goal setting Supervising parents Trusted adult School engagement Sports Involvement in church or other activities

And remember, Biology is not Destiny

Dr. Cynthia Kuhn ckuhn@duke.edu

Effects of Addictive Drugs are a Balance of Reward and Aversion Initial Drug Experience: DA dominant Addiction: CRF Dominant CRF: Amygdala DA