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

2. 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

3. Tobacco Use is Maximal in Adolescence

4. Addictive Drug Use Peaks during Adolescence

5. Alcohol Use Peaks during Late Adolescence

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

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

8. Adolescent Brain is Still Changing

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

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

11. Triad of Motivated Behavior
Executive
Function
Reward
Avoidance

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

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

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

15. Reward is More Effective than Punishment in Adolescence
Adult

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

17. Adolescents Do Not Avoid Bad Outcomes

18. Adolescents are Impulsive

19. 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

20. 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

21. So Is the Brain Primed for Addiction in Adolescence?

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

23. 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

24. Neural Basis of Addiction
Dopamine

25. All Addictive Drugs Activate This CircuitDA
Cocaine
Alcohol
Heroin
Nicotine

26. All Addictive Drugs Increase Dopamine Levels

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

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

29. Dopamine Receptors Are Decreased in Addicts

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

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

32. 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)

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

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

35. 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

36. 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

37. What is Different in Adolescent Response to Addictive Drugs?

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

39. Adolescents Avoid Drugs that are Aversive Less than Adults

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

41. 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

42. Not Every Adolescent is Equally at Risk

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

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

45. Does This Mean that Behavior Changes is Impossible? NO

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

47. 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

48. And remember, Biology is not Destiny

49. Dr. Cynthia Kuhn

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