2. Alcohol and the Adolescent Brain Ken Winters, Ph.D. Department of Psychiatry University of Minnesota winte001@umn.edu U.S.E.D. Grants to Reduce Alcohol Abuse Conference November 18, 2003

3. U of Minnesota, Center for Adolescent Substance Abuse Research Staff are all above average. Women are strong. Men are good looking. Our ex-Governor was a professional wrestler

4. 3. Adolescence and the Brain 4. Brain and Alcohol 5. Youth, Brain and Alcohol Are adolescents more susceptible to alcohol than adults? 1. Developmental Issues2. Brain Functioning Is addiction a brain disorder? 6. Prevention and Treatment

5. 1. Developmental Issues

6. Alcohol Use Youth alcohol use occurs on a continuum Most youth have used some alcohol Alcohol Use by Youth 7 million teens binge drink at least once a month

7. Trends in prevalence of drugs for 12th graders: 1994 to 2001 30-Day Year Alcohol % 1994 50.1 1995 51.3 1996 50.8 1997 52.7 1998 52.0 199951.0 200050.0 200149.8 MTFS, 1975-2001

8. Alcohol Problems Alcohol Use Disorders (AUDs) are Relatively Rare AUD rates vary; 3-10% Most youth who use do not meet criteria for abuse or dependence boy AUD rates > girl AUD rates

9. Long-Term, Heavy Use of Alcohol  Significant shrinking of the brain  50% - 75% show cognitive impairment  Effects remain even after detoxification & abstinence  Alcohol dementia is 2 nd- leading cause of adult dementia

10. Trends in prevalence of drugs for 12th graders: 1994 to 2001 Daily Year Cigarettes % 1994 19.4 1995 21.7 1996 22.2 1997 24.5 1998 22.5 1999 23.1 2000 20.5 2001 19.0 MTFS, 1975-2001

11. Marijuana: Trends in Perceived Availability, Perceived Risk, and Use for 12th Graders Percent MTFS, 1975-2001 Availability= Fairly easy or very easy to get Risk = Great risk of harm in regular use Use= Once or more, past 30 days

12. Non-Medical Use of Prescription Drugs The rapid rise in use of club drugs, methamphetamine, and oxycodone has put a spotlight on the non-medical use of prescription drugs. Increase by 11 % in 2001 compared to previous year. Exceeds combined use of heroin, cocaine, crack and hallucinogens.

13. Comorbid Disorders with AUD Alcohol Use Disorder Depression Gambling Oppositional Defiance Disorder Conduct Disorder ADHD Anxiety Many predate onset of AUD > comorbidity, >AUD Relapse > if comorbidity Medication may be appropriate

14. Individuation need to develop personal identity Separation need to separate from parents Developmental Phases of Adolescence These forces can disrupt our prevention and treatment efforts

15. Stages of Change Prochaska and DiClimente PrecontemplationAction

16. Stages of Change for Most Youth? Precontemplation

17. Working with parents

19. 1. Developmental Issues2. Brain Functioning

20. What a Machine!  100 billion neurons in the brain  Cortex is 1/8 inch thick like bark – 80% of it is neurons  Fastest brain messages = 360 mph  Over 90 neurochemicals are involved in transmission of impulses across neurons

21. Brain Functioning  Humans are “wired” with nerve cells (neurons)  Neurons group together to form strands (up to 4 feet long)  Strands perform specific function  They extend from brain to spinal cord

22. Brain Functioning  Strands are not continuous - they have small spaces in between  Spaces are called synapses  Neurons pass messages through the synapse with chemicals  Chemicals are called neurotransmitters  Drugs affect neurotransmitters

23. “The 3 pound organ that rules the body is finally giving up its secrets” (TIME, August, 2001)  1990’s information explosion MRI PET CAT  These brain imaging techniques produce windows to observe the effects of substances on the brain

24. Imaging Modalities CT SPECTFDG PETLigand PET Anatomic MRI MR Spectroscopy fMRIDiffusion MRI

25. Your Brain on Alcohol 1-2 Min3-45-6 6-77-88-9 9-1010-2020-30

26. Your Brain After Drugs Normal Alcohol Abuser Alcoholic

27. 3. Adolescence and the Brain 1. Developmental Issues2. Brain Functioning

28. The Adolescent Brain is Still Developing  During adolescence, the brain is undergoing dramatic transformations  In some brain regions, over 50 % of neuronal connections are lost  Some new connections are formed  Net effect is pruning (a loss of neurons)

29. Adolescent Brain Changes  These brain changes are relevant to adolescent behavior  Prefrontal cortex (PFC) is pruned; not fully developed until mid-20’s  Amygdala (and n.a.) show less pruning and tend to dominate the PFC judgment reward system amygdala nucleus accumbens prefrontal cortex

30. NOT GOOD NEWS!  planned thinking  impulsiveness  self-control  risk-taking PFC amygdala “hot” decisions more likely than “cold” decisions I like to use drugs! !

31. PFC amygdala In the presence of stress… I hate school; I am going to skip classes and get drunk

32. PFC amygdala GOOD NEWS! The pruning of the PFC neurons produces a more efficient PFC by young adulthood I am planning for the future

34. 3. Adolescence and the Brain 4. Brain and Alcohol 1. Developmental Issues2. Brain Functioning Is addiction a brain disorder?

35. From “Oops” to Dependence

36. “Oops Phenomenon”  First use to “FEEL GOOD”  Some continue to compulsively use because of the reinforcing effects (e.g., to “FEEL NORMAL”)  Changes occur in the “reward system” that promote continued use

37. Reward System  The reward system is responsible for seeking natural rewards that have survival value  seeking food, water, sex, and nurturing  Dopamine is this system’s primary neurotransmitter reward

38. Drugs Hijack the Brain’s Reward Circuitry  Continued use of alcohol reduces the brain’s dopamine production.  Because dopamine is part of the reward system, the brain is “fooled” that alcohol has survival value for the organism.  The reward system responds with “drug seeking behaviors”  Craving occurs and, eventually, dependence. reward ‼

39. Evidence  Animal Studies:  electrodes attached to “Reward Circuit”  animals press lever to receive stimuli to brain  they continue until collapse from exhaustion  Behavioral Genetics Studies:  heredity plays a role  identical twins: > chance of becoming alcoholics than fraternal twins  adoptive children of alcoholics: > chance of becoming alcoholic; even true when raised by non-alcoholic parents  further research needed by gender

40. Human Studies: amygdala has memory of the drug after discontinuation. Nature VideoAlcohol Video Front of Brain Back of Brain amygdala not lit up amygdala activated

41. 3. Adolescence and the Brain 4. Brain and Alcohol 5. Youth, Brain and Alcohol Are adolescents more susceptible to alcohol than adults? 1. Developmental Issues2. Brain Functioning Is addiction a brain disorder?

42. Are adolescents more susceptible to alcohol than adults?  Adult studies suggest that the areas of the adolescent brain that are remodeled are sensitive to the effects of alcohol Difficult scientifically and ethically to study adolescent sensitivity to alcohol amygdala nucleus accumbens prefrontal cortex

43. Are adolescents more susceptible to alcohol than adults?  Animal models can be easily used to explore this issue  Role of psychosocial factors can not be studied

44. Are adolescents more susceptible to alcohol than adults? 1.Adolescent rats are less sensitive to effects of intoxication and less sensitive to the “hangover” that follows use

45. Are adolescents more susceptible to alcohol than adults? 2.Adolescent rats are more sensitive to the social disinhibition induced by alcohol use Wanna look for some cheese with me? Sure!

46. Are adolescents more susceptible to alcohol than adults? 3.Adolescent drunk rats perform worse on memory tasks than adult drunk rats Ugh? ? disrupts the hippocampus brain damage in the PRF converts information to memory planne d thinkin g

47. Supporting Human Studies 1. Reduced sensitivity to intoxication 2. Increased sensitivity to social disinhibitions 3. Greater adverse effects to cognitive functioning 1. Reduced sensitivity to intoxication 3. Greater adverse effects to cognitive functioning

48. Survey Data Suggest that Adolescents Are More Sensitive to Alcohol Monitoring the Future, 2001

49. Alcohol’s Effects  Adolescents with a history of extensive use…. Hippocampus (50%) brain activity during memory tasks brain activation when shown alcohol images converts informatio n to memory trigger for relapse (Brown, 2002; Wuethrich, 2001)

50. Are adolescents more susceptible to alcohol than adults? 4.Hyperexcitability issue

51. Are adolescents more susceptible to alcohol than adults? 4. Hyperexcitability issue  Alcohol relieves hyperexcitability state  Relief is temporary; continued seeking of alcohol is reinforced  Hyperexcitability is a key characteristic of conduct disorders, ADHD & other impulsive behaviors  Found in non-alcoholic relatives - suggests inheritance of brain wave patterns ADHD ODD Con Dis Sub Use Dis

52. Are adolescents more susceptible to alcohol than adults? 1Reduced sensitivity to intoxication 2Increased sensitivity to social disinhibitions 3Greater adverse effects to cognitive functioning 4Medicates “excitability” Most certainly YES

53. PFC amygdala “hot” decisions more likely than “cold” decisions I like to use drugs! ! Less We Forget: The Adolescent Brain is Susceptible

54. Key Concepts 3. Adolescence and the Brain 4. Brain and Alcohol 5. Youth, Brain and Alcohol Are adolescents more susceptible to alcohol than adults? 1. Developmental Issues2. Brain Functioning Is addiction a brain disorder? 6. Prevention & Treatment

55. Implications for Prevention and Treatment  Prevention  The earlier the better  Educate them about the susceptibility of the adolescent brain and alcohol exposure  Skills training in the context of competing “voices” (PFC vs amygdala)

56. Marijuana: Trends in Perceived Availability, Perceived Risk, and Use for 12th Graders Percent MTFS, 1975-2001 Availability= Fairly easy or very easy to get Risk = Great risk of harm in regular use Use= Once or more, past 30 days

57. Implications for Treatment  Psychosocial treatment  Verbal skills required in therapy may be compromised  Behavioral demands of self- control and relapse prevention may be compromised  Medications are being clinically tested to...  Decrease anxiety and depression associated with initial stages of recovery  Decrease desire to drink  Treat co-existing disorders NALTREXONE, ACAMPROSATE, SSRI’S

58. Is Addiction a Brain Disorder?Evidence to Support a “Yes”

59. When working with teenagers, remember… Adolescence is a time limited disorder

60. THANK YOU! winte001@umn.edu

61. extras

62. References  Leshner A. Oops. How casual drug use leads to addiction. National Institute on Drug Abuse web site: www.drugabuse.gov/Published_Articles/Oops.html September, 2000.  National Institute on Alcohol Abuse and Alcoholism. Imaging and Alcoholism: A Window on the Brain. Alcohol Alert No. 47, April 2000.  National Institute on Alcohol Abuse and Alcoholism. Tenth Special Report to the U.S. Congress on Alcohol and Health, NIH Pub. No. 00- 1583, 2000.  National Institute on drug Abuse. Principles of drug addiction treatment: A research-based guide. No. 99-4180, 1999.

63. From Discover vol. 22, No. 3, March 2001 Meta analysis by Bernice Wuethrich  7 million youths between ages 12 and 20 binge drink at least once a month  Teen drinkers most susceptible to damage in the hippocampus and the prefrontal cortex  The hippocampus is 10% smaller in teens who use alcohol  Alcohol blocks long term potentiation in adolescent brain tissue; the production of glutamate which is responsible for memory formation  The impact on the developing brain continues through the early twenties  It is suspected that the physical impact of withdrawal – cell death and increase in number and sensitivity of hyperactive receptors – creates the brain damage. Brown, 2002; Wuethrich, 2001

64. American Medical Association, 2002 Sandra Brown, Ph.D., San Diego, Veterans Affairs Medical Center  Drinking at a young age can impair memory development and the ability to learn permanently  Research matched 56 adolescent drinkers with 56 non-drinkers  When given standardized test the drinkers scored worse in vocabulary, general information, memory and memory retrieval  Problems continued through years of follow-up