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

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

2. Presentation Objectives • Identify impact of substance abuse & addiction • Examine contribution of nature vs. nurture • Explain how drugs “work” • Understand how prolonged drug use changes brain circuitry • Understand how appropriate treatment can help people recover from drug abuse and addiction.

3. Addiction Medical Medical Neurotoxicity AIDS, Cancer Mental illness NEUROTOXICITY AIDS CANCERMENTAL ILLNESS DRUGS Economic Social Health care Productivity Accidents Homelessness Crime Violence

4. 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.

5. 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.

6. 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.

7. The Perpetrator is Involved in Drug Use in… • 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.

8. However…advances in science have revolutionized our fundamental views of drug abuse and addiction, showing us that: ► abuse is a preventable behavior ► addiction is a treatable disease

9. used to be

10. 1-2 Min 3-4 5-6 6-7 7-8 8-9 9-10 10-20 20-30 Your Brain on Drugs Today YELLOW shows places in brain where cocaine goes (striatum) Front of Brain Back of Brain Fowler et al., Synapse, 1989.

11. Common Myths About Drug Abuse… • Drug abuse equates to drug addiction • Alcohol is not a drug • Addiction is a moral weakness • You have to hit rock bottom to recover • You have to want treatment for it to be successful • Drug abuse is more common among minorities

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

13. Why Do People Take Drugs in The First Place? To feel better To lessen: anxiety worries fears depression hopelessness To feel good To have novel: feelings sensations experiences AND to share them

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

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

16. Biology/genes Biology/ Environment Interactions Environment

17. DA Receptors and the Response to Methylphenidate (MP) High DA receptor high Dopamine receptor level low Low DA receptor 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.

18. Drug Abuse Drug/Alcohol Related Traffic Accidents Delinquency CommunityPeer ClusterFamilyIndividual Sexually Transmitted Diseases (Including HIV/AIDS) Academic Failure and DroppingOut of School Suicidal Behavior Juvenile Depression Unwanted Pregnancies Running Away From Home

19. How Do Drugs “Work”?

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

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

23. Mediodorsal Thalamus Basolateral Amygdala Prefrontal Cortex Nucleus Accumbens Ventral Pallidum Motor Nuclei Ventral Tegmental Area GABA and Glutamate Role in Motivation Dopamine GABA Glutamate Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.

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

25. Alcohol vs. Other Drugs We know that alcohol impairs the brain and results in addiction with repeated use in the same way as other drugs

26. = vesicle Precursor = neurotransmitters Synthesis = receptor Storage Degradation Reuptake Release Synaptic Cleft

28. dopamine transporters

29. 15 10 Copulation Frequency 5 0 Mounts 1 2 3 4 5 6 7 8 Intromissions Ejaculations Natural Rewards Elevate Dopamine Levels SEX FOOD 200 200 NAc shell 150 150 DA Concentration (% Baseline) 100 100 % of Basal DA Output Empty 50 Box Feeding 0 0 60 120 180 Female Present Time (min) Sample Number Di Chiara et al., Neuroscience, 1999. Fiorino and Phillips, J. Neuroscience, 1997.

31. Effects of Drugs on Dopamine Release COCAINE AMPHETAMINE Accumbens 1100 Accumbens 400 1000 900 DA 800 DA 300 DOPAC 700 DOPAC % of Basal Release HVA HVA 600 % of Basal Release 500 200 400 300 100 200 100 0 0 0 1 2 3 4 5 hr Time After Amphetamine Time After Cocaine NICOTINE MORPHINE 250 Accumbens 250 Dose (mg/kg) 200 Accumbens 0.5 200 Caudate 1.0 2.5 % of Basal Release 150 % of Basal Release 10 150 100 0 1 2 3 hr 100 0 1 2 3 4 5 hr 0 0 0 1 2 3 4 5hr Time After Nicotine Time After Morphine Di Chiara and Imperato, PNAS, 1988

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

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

34. 2.0 1.8 1.6 1.4 1.2 Dopamine Transporter Time Gait Bmax/Kd 1.0 7 8 9 10 11 12 13 (seconds) 2.0 1.8 1.6 1.4 1.2 Delayed Recall (words remembered) 1.0 16 14 12 10 8 6 4 Dopamine Transporters in Methamphetamine Abusers Motor Task Loss of dopamine transporters in the meth abusers may result in slowing of motor reactions. Normal Control Memory task Loss of dopamine transporters in the meth abusers may result in memory impairment. Volkow et al., Am. J. Psychiatry, 2001. . Methamphetamine Abuser

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

36. 2.5 Conditioned Association N = 13 2.0 5 4 3 2 1 0 -1 1.5 DCRAVING 1.0 Neutral Cocaine .5 STIMULI 0 Nature Video Cocaine Video CRAVING INDUCTION IN A PET SETTING Childress et al., Am. J. Psychiatry, 1999

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

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

39. Drugs Are Usurping Brain Circuits and Motivational Priorities

40. Treatment and the Cycle of Addiction

41. Addiction is the Quintessential Biobehavioral Disorder

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

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

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

45. Treating a Biobehavioral Disorder Must Go Beyond JustFixing the Chemistry • Pharmacological (medications) • Behavioral Therapies • Medical and Social Services

46. We Need to Treat the Whole Person! In Social Context

47. Treatment Can Work

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

49. 100 90 80 70 60 Percent of Patients Who Relapse 50 40 30 50 to 70% 50 to 70% 40 to 60% 30 to 50% 20 10 0 Drug Addiction Type I Diabetes Asthma Hypertension Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses McLellan et al., JAMA, 2000.

50. 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…