1. Addiction: It’s a Brain Disease Beyond a Reasonable Doubt

2. Estimated Economic Cost to Society from Substance Abuse and Addiction: Illegal drugs: $181 billion/year Alcohol: $185 billion/year Tobacco: $158 billion/year Total: $524 billion/year Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000.

3. Contributors to the Economic Costs of Substance Abuse and Addiction Health care expenditures –Alcohol and drug abuse services –Medical consequences Productivity (lost earnings) –Premature death –Impaired job performance –Institutionalized population –Incarceration –Criminal victimization Other impacts on society –Crime –Social welfare administration –Vehicular accidents Adapted from Harwood et al., Addiction, 1999.

4. Between 50% and 80% of Adult Male Arrestees Tested Positive for Illicit Drug Use in 2000 Drug Use Correlates with Crime 2000 Arrestee Drug Abuse Monitoring: Annual Report, April 2003.

5. More than 50% of violent crimes 60-80% of child abuse and neglect cases 50-70% of theft and property crimes 75% of drug dealing Belenko and Peugh, 1998; National Institute of Justice, 1999. The Perpetrator is Involved in Drug Use in…

6. What is Addiction? A brain disease expressed as a compulsive behavior The continued abuse of drugs despite negative consequences A chronic, potentially relapsing disorder

7. 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

9. Why do some people become addicted while others do not? Vulnerability

10. There’s a Big Genetic Contribution to Drug Abuse and Addiction… Drug Abuse and Addiction… ….Overlapping with Environmental Influences that Help Make Addiction a Complex Disease.

11. high low High DA receptor Low DA receptor DA Receptors and the Response to Methylphenidate (MP) As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999. Dopamine receptor level

12. How Do Drugs “Work”?

13. Initially, a person takes a drug hoping to change his or her mood, perception, or emotional state Translation – …hoping to change their brains.

14. We know that despite their many differences, most abused substances enhance the dopamine and serotonin pathways

16. Circuits Involved In Drug Abuse and Addiction All of these must be considered in developing strategies to effectively treat addiction All of these must be considered in developing strategies to effectively treat addiction

18. dopamine transporters

19. 0 50 100 150 200 060120180 Time (min) % of Basal DA Output NAc shell Empty BoxFeeding Di Chiara et al., Neuroscience, 1999. FOOD Mounts Intromissions Ejaculations Fiorino and Phillips, J. Neuroscience, 1997. Natural Rewards Elevate Dopamine Levels 100 150 200 DA Concentration (% Baseline) 15 0 5 10 Copulation Frequency Sample Number 12345678 SEX Female Present

21. 0 100 150 200 250 0123 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE Di Chiara and Imperato, PNAS, 1988 Effects of Drugs on Dopamine Release

22. prolonged drug use changes the brain in fundamental and long-lasting ways Science has generated much evidence showing that…

23. DA D2 Receptor Availability Control Addicted Cocaine Alcohol DA Reward Circuits DA Reward Circuits DA Drug Abuser Non-Drug Abuser Heroin Meth Dopamine D2 Receptors are Lower in Addiction DA

24. Dopamine Transporters in Methamphetamine Abusers Normal Control Methamphetamine Abuser Motor Task Loss of dopamine transporters in the meth abusers may result in slowing of motor reactions. Memory task Loss of dopamine transporters in the meth abusers may result in memory impairment. 78910111213 1.0 1.2 1.4 1.6 1.8 2.0 Time Gait (seconds) 46810121416 1.0 1.2 1.4 1.6 1.8 2.0 Delayed Recall (words remembered) Dopamine Transporter Bmax/Kd Volkow et al., Am. J. Psychiatry, 2001..

25. Implication: Brain changes resulting from prolonged use of drugs may compromise mental and motor functions

26. Nature Video Cocaine Video Conditioned Association Conditioned Association 1.5 0.5 1.0 2.0 2.5 CRAVING INDUCTION IN A PET SETTING N = 13  CRAVING 5 4 3 2 1 0 Neutral Cocaine STIMULI Childress et al., Am. J. Psychiatry, 1999

27. Memories Appear to Be A Critical Part of Addiction “Its about people, places and things…”

28. Cocaine Film Cocaine Craving: Population (Cocaine Users, Controls) x Film (cocaine, erotic) Garavan et al., Am. J. Psychiatry, 2000. IFG Ant. Cing. Cingulate Signal Intensity (AU) Controls Cocaine Users

29. Drugs Are Usurping Brain Circuits Brain Circuits andMotivational Priorities Priorities

30. Treatment and the Cycle of Addiction

31. Addiction is the Quintessential Biobehavioral Disorder

32. Drugs Brain Mechanisms Behavior Environment Psychological Environmental - Prior experience - Expectation - Learning - Social interactions - Stress - Conditioned stimuli - Genetics - Circadian rhythms - Disease states - Gender Physiological Drug Addiction: A Complex Behavioral and Neurobiological Disorder

33. Source: Adapted from Volkow et al., Neuropharmacology, 2004. Drive Saliency Memory Control Non-Addicted Brain NOT GO Addicted Brain Drive Memory Control GO Saliency Addiction Changes Brain Circuits

34. This is why treatment is essential This is why addicts can’t just quit

35. Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry Pharmacological (medications) Behavioral Therapies Medical and Social Services

36. Treatment Can Work

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

38. Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses Drug Addiction Type I Diabetes 0 10 20 30 40 50 60 70 80 90 100 Hypertension Asthma 40 to 60% 30 to 50% 50 to 70% Percent of Patients Who Relapse McLellan et al., JAMA, 2000.

39. Addiction is Similar to Other Chronic Illnesses Because: Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments Relapses to drug abuse can occur during or after successful treatment episodes Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery Therefore…

40. Hypertension Tx Stage of Tx YES Addiction Tx Stage of Tx NO There is a right way and a wrong way to Measure the Outcome of Treating Chronic Illnesses like Addiction

41. Full recovery is a challenge but it is possible …

42. DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (14 month abstinent)

43. Treatment Reduces Drug Use and Recidivism No treatment CREST Dropouts CREST Completers + Aftercare No treatment CREST Dropouts CREST Completers + Aftercare Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to No Treatment group Percentage of Participants Drug-Free Arrest-Free