2. 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%

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

4. Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179 MRI Scans of Healthy Children and Teens Over Time

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

6. Do Adolescents React Differently than Adults to Substances of Abuse?

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

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

9. Americans’ Views of the Seriousness of Health Problems (Top 10 of 36 Problems) 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

10. Definitions Drug Use –Taking a psychoactive substance for non-medical purposes, out of curiosity Drug Abuse –Drug use that leads to problems (e.g. loss of effectiveness in society; behavioral psychopathology, criminal acts) Drug Dependence –A maladaptive pattern of drug use leading to clinically-significant impairment or distress, associated with difficulty in controlling drug-taking behavior, withdrawal, and tolerance –The state of needing a drug to function within ‘normal limits’

11. Nature of Addiction - a continuum of use? However, addiction is more than mere drug use… Loss of control 

12. 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:

13. Addiction Involves Multiple Factors

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

15. Physical vs. Psychological Dependence Physical Dependence –Withdrawal symptoms in the absence of the drug –Tolerance to its effects with repeated use Psychological 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)

16. 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.”

17. 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 accumbens –Animals will work to micro-inject drugs of abuse and electrically stimulate the same parts of the brain –Normal rewards (food, drink, sex) also stimulate DA release

19. Drug Dependence Among Ever-Users 010203040 Marihuana Stimulants Alcohol Cocaine Heroin Tobacco % Dependent

20. 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

21. 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

22. 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

23. 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

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

25. We Need to Keep Our Eye on the Real Target the Real Target Abstinence Functionality in Family, Work and Community In Treating Addiction…

26. Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways 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 Disease Transmission IV Drug Use Drug User Disinhibition Leading to High Risk Sexual Behaviors Progression of Disease

27. 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

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

29. Targets of Medication Methadone, LAAM and Buprenorphine Activate opioid receptors Nicotine gum/patch Activate nicotinic receptors Naloxone Block opioid receptors