NEUROBIOLOGY OF ADDICTION

NEUROBIOLOGY OF ADDICTION Petros Levounis, MD, MA Chair Department of Psychiatry Rutgers New Jersey Medical School Rutgers New Jersey Medical School Fundamentals of Addiction Medicine Summer Series Newark, NJ July 3, 2013

Outline 1. Neurobiology of Addiction 2. Psychotherapy of Addiction 3. Principles of MI 4. Practice of MI 5. Addiction Pharmacotherapy 6. Conclusions 2

1 Neurobiology of Addiction 3

~ 2000 4

The Fundamental Model Biological Psychological Social Use Brain Switch Addiction Relapse 1. Stress 2. Triggers (Cues) 3. Exposure (Primers) 5

Natural Rewards and Dopamine Levels % of Basal DA Output 200 150 100 50 0 Food Empty Box Feeding 0 60 120 180 Time (min) DA Concentration (% Baseline) 200 150 100 Sample Number Sex Female Present 1 2 3 4 5 6 7 8 Adapted from: Di Chiara et al, Neuroscience, 1999 Adapted from: Fiorino and Phillips, J Neuroscience, 1997 6

Effects of Drugs on Dopamine Levels % of Basal Release 250 200 150 100 0 MORPHINE Dose mg/kg 0.5 1.0 2.5 10 0 1 2 3 4 5 hr % of Basal Release 400 300 200 100 0 COCAINE 0 1 2 3 4 5 hr % of Basal Release 250 200 150 100 NICOTINE % of Basal Release 250 200 150 100 ETHANOL Dose (g/kg ip) 0.25 0.5 1 2.5 0 0 1 2 3 hr 0 1 2 3 4hr Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of Nora D Volkow, MD 0 7

Effects of Drugs on Dopamine Levels 1100 % of Basal Release 1000 900 800 700 600 500 400 AMPHETAMINE DA 300 200 100 0 0 1 2 3 4 5 hr Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of Nora D Volkow, MD 8

Pleasure-Reward Pathways Frontal Cortex Striatum Hippocampus Nucleus Accumbens Ventral Tegmental Area 9 Adapted from: National Institute on Drug Abuse, www.nida.nih.gov, 2000

2013 10

Neural Circuitry of Addiction Frontal Cortex Striatum Hippocampus 11 Koob, Pharmacopsychiatry, 2009

1. Addiction Neurotransmitters 1. Dopamine 2. Glutamate 3. γ-aminobutyric Acid (GABA) 4. Serotonin 5. Norepinephrine 6. Corticotropin-Releasing Factor (CRF) 7. Opioids 8. Cannabinoids Koob, J Drug Issues, 2009 12

2. Motivation: More than an Amoeba Adapted from: Flaherty, Coaching: Evoking Excellence in Others, 2005; graphic by Lukas Hassel. 13

3. The Anti-Reward Pathways 14 Volkow ND and Baler RD, Neuropharmacology, 2013.

Reward and Antireward Systems Gardner, Chronic Pain and Addiction, 2011 15

Reward Systems GAME 1 A. A sure gain of $250. B. 25% chance to gain $1,000, 75% chance to gain nothing. 84% 16% 16 Adapted from: Tversky and Kahneman, Science, 1981

Antireward Systems GAME 2 A. A sure loss of $750. B. 25% chance to lose nothing, 75% chance to lose $1,000. 13% 87% 17 Adapted from: Tversky and Kahneman, Science, 1981

MATHEMATICS GAME 1 25% + 750 25% - 250 25% - 250 25% - 250 GAME 2 25% + 750 25% - 250 25% - 250 25% - 250 18

HUMAN NATURE People avoid risks to ensure gains (even small gains). People take risks (even big risks) to avoid definite losses. Psychology trumps probability. 19

2 A Brief History of the Psychotherapy of Addiction 20

1 st Wave: Psychoanalysis 1. Psychoanalysis works for all treatable mental illness. 2. Psychoanalysis does not work for addiction. 3. Therefore, addiction cannot be treated. 21

2 nd Wave: Boot Camps The prototype, Synanon, was founded in California in 1958 to address heroin addiction. The goal was to: break down defenses, bust through denial, and reshape the addict s personality. 22

2 nd : Therapeutic Communities 1. Shaving heads 2. Hanging humiliating signs around residents necks 3. Subjecting patients to encounter groups involving loud, free flowing attacks from staff and fellow residents 23

3 rd Wave: Modified TCs During the 1970s and 1980s, most Therapeutic Communities evolved beyond the Synanon model. People started recognizing the limits and dangers of confrontive techniques. 24

3 rd : Cognitive-Behavior Therapy 1. Based on Operant Conditioning 2. Functional Analysis 3. Skills Training to: identify, avoid, and cope with thoughts & cravings Kadden, Cognitive-Behavioral Coping Skills Therapy Manual: A Clinical Research Guide for Therapists Treating Individuals with Alcohol Abuse and Dependence, 1992 25

The Frying Pan Revisited 26 Volkow et al, J Neuroscience, 2001

4 th : The Kitchen Sink Approach 1. 12-step Facilitation 2. Relapse Prevention 3. Family Therapy 4. Primary Care 5. Mental Health Services 6. Aftercare Nunes, Selzer, Levounis, Davies, Substance Dependence and Co-Occurring Psychiatric Disorders, 2010. 27

12-Step Facilitation 28

The AA Elevator Slogan 1. Spiritual Health 2. Professional and Vocational Health 3. Interpersonal and Family Health 4. Mental Health 5. Physical Health 6. Life 29

Medical Student Attitudes STUDENTS 1. Housing 2. Gov t Svcs 3. Medical Svcs 4. Outpatient Svcs 5. Job 6. Community 7. Trusting People 8. Inner peace 9. God 10. Spirituality 11. AA PERCEPTION 1. Housing 2. Outpatient Svcs 3. Medical Svcs 4. Job 5. Trusting People 6. AA 7. Inner Peace 8. Community 9. Gov t Svcs 10. Spirituality 11. God PATIENTS 1. Inner peace 2. God 3. Medical Svcs 4. AA 5. Housing 6. Spirituality 7. Outpatient Svcs 8. Community 9. Gov t Svcs 10. Trusting People 11. Job 30 Goldfarb, Am J Drug Alcohol Abuse, 1996.

Psychiatric Co-Morbidities 1. A third to two thirds of addicted people also suffer from another mental illness not 10%, not 90%. 2. Treat both the addiction and the cooccurring psychiatric disorder(s). 3. Avoid benzodiazepines and use antidepressants as first line treatments for anxiety disorders. 31

The Four-Quadrant Model 32

3 Principles of Motivational Interviewing 33

Motivation 1. People are unmotivated vs. People are always motivated for something. 2. Why isn t the person motivated? vs. For what is the person motivated? 34 Miller and Rollnick, Motivational Interviewing: Helping People Change, 3 rd Edition, 2012.

Ambivalence 1. Ambivalence is normal; needs to be explored, not confronted. 2. Ambivalence is a reasonable place to visit, but you wouldn t want to live there. 35 Miller and Rollnick, Motivational Interviewing: Helping People Change, 3 rd Edition, 2012.

Principles REDS 1. Roll with Resistance 2. Express Empathy 3. Develop Discrepancy 4. Support Self-Efficacy 36 Miller and Rollnick, Motivational Interviewing: Preparing People for Change, 2 nd Edition, 2002.

MI Today Beyond REDS Engaging Focusing Evoking Planning 37 Miller and Rollnick, Motivational Interviewing: Helping People Change, 3 rd Edition, 2012.

4 Practice of Motivational Interviewing 38

Phases PHASE 1: Building Motivation for Change PHASE 2: Strengthening Commitment to Change and Developing a Plan. 39

The Stages of Change 1. Precontemplation 2. Contemplation 3. Preparation 4. Action 5. Maintenance 6. Relapse Prochaska and DiClemente, The Transtheoretical Approach: Crossing Traditional Boundaries of Therapy, 1984. 40

The Stages of Change Cycle 41 Levounis and Arnaout, Handbook of Motivation and Change: A Practical Guide for Clinicians, 2010. 41

Working the Stages 1. Identify the Stage of Change. 2. Help the person move a little bit forward. 3. Don t rush her or him. 42 Levounis and Arnaout, Handbook of Motivation and Change: A Practical Guide for Clinicians, 2010.

Precontemplation 1. Plant the seed of ambivalence. 2. Techniques: Ask for a description of a typical day. Hunt for the smallest discrepancy between where people are and where they would like to be. 43

The Readiness Ruler Adapted from: Miller and Rollnick, Motivational Interviewing: Preparing People for Change, 2 nd Edition, 2002, Graphic by Dr. Chris Welsh. 44

Contemplation 1. Open up to explosive decision analysis. 2. Techniques: Brainstorm widely. Explore both positive and negative prospects of life with and without the proposed changes. 45

The Decisional Balance Levounis and Arnaout, Motivational Interviewing: Preparing People for Change, 2 nd Edition, 2002, Graphic by Dr. Chris Welsh. 46

Preparation 1. Develop a realistic action plan. 2. Techniques: Anticipate problems and identify solutions. Unforeseen complications and frustrating obstacles may require revisiting contemplation stage techniques. 47

Action 1. Based on principles of learning, replace maladaptive patterns of behaving and thinking. 2. Techniques: Essentially use a CBT model. Provide ample positive feedback, encouragement, and support. 48

Maintenance 1. Back to the kitchen sink approach. 2. Techniques: Recruit motivational, cognitivebehavioral, regulatory, disciplinary, and social approaches to sustain the desired change. Explore disappointments, temptations, and doubts. 49

Relapse 1. Remember Confucius: Our greatest glory is not in never falling but in rising every time we fall. 2. Techniques: Accept relapse as an opportunity to reengage, rethink, and reemerge stronger than before. Reengage quickly, even if it is to the expense of deeper rethinking. 50

Technique: Reflective Listening Make a guess as to what the patient means. Skillful listetning moves past what the person exacly said, without jumping too far. Like interpretations in dynamic therapy, if the patient becomes defensive, you know that you jumped too far, too fast. Levounis and Arnaout, Handbook of Motivation and Change: A Practical Guide for Clinicians, 2010. 51

Technique: Elicit Change Talk As a person argues on behalf of one position, she or he becomes more committed to it; we literally talk ourselves into (or out of) things. This may explain why the more resistance is evoked during a counseling session, the more likely it is that a person will continue to use. Levounis and Arnaout, Handbook of Motivation and Change: A Practical Guide for Clinicians, 2010. 52

Practical Suggestions 1. Listen > Ask > Give advice 2. Talk less than the patient. 3. Do not ask more than 3 consecutive questions. 4. Avoid wordiness. 5. Avoid interrupting. 6. Cooperate, do not force knowledge. 7. Relax. Levounis and Arnaout, Handbook of Motivation and Change: A Practical Guide for Clinicians, 2010. 53

5 An Even Briefer History of Addiction Pharmacotherapy 54

Two Main Strategies 1. Agonists Nicotine Replacement Therapies Methadone for Opioids 2. Antagonists Naltrexone for Opioids 55 Renner and Levounis, Office-Based Buprenorphine Treatment of Opioid Dependence, 2011

The New Strategy Partial Agonists Varenicline for Nicotine Buprenorphine for Opioids 56 Renner and Levounis, Office-Based Buprenorphine Treatment of Opioid Dependence, 2011

The Ceiling Effect 100 % Efficacy 90 80 70 60 50 40 30 20 10 0 Full Agonist (Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone) -10-9 -8-7 -6-5 -4 Log Dose of Opioid 57

6 Conclusions 58

1. Addiction hijacks both the pleasure/reward and anti-reward pathways of the brain. 2. Antireward pathways are likely responsible for the sustaining addiction. 3. Motivation has replaced confrontation as the primary focus of addiction treatment. 4. Motivational Interviewing is based on exploring and resolving ambivalence. 59

Thank you 60