Rutgers New Jersey Medical School Opioid Crisis in America: A Big Mistake, an Aggressive Industry, a Tricky Brain, and the 16 Milligrams that Will Bring Your Child Back to College Petros Levounis, MD, MA Professor and Chair Rutgers New Jersey Medical School Newark, New Jersey San Antonio, Texas: August 21 to 23, 2017

Learning Objectives After attending this presentation, learners will be able to: Describe the basic model of addiction. List three safe and effective treatments for opioid use disorder. Discuss mindfulness in the treatment of addiction.

Outline The Basic Model The Neurobiology of Addiction Addiction Treatments New Directions Conclusions

1 The Basic Model

A Biopsychosocial Illness Biological Addiction Psychological Social Brain Switch Use Olsen and Levounis, Sober Siblings, 2008. 5

The Root Cause of the Disaster Porter and Jick, N Engl J Med, January 10, 1980.

Pharma

Primary non-heroin opioid admission rates (per 100,000) Admissions: 1999 Primary non-heroin opioid admission rates (per 100,000)

Primary non-heroin opioid admission rates (per 100,000) Admissions: 2001 Primary non-heroin opioid admission rates (per 100,000)

Primary non-heroin opioid admission rates (per 100,000) Admissions: 2003 Primary non-heroin opioid admission rates (per 100,000)

Primary non-heroin opioid admission rates (per 100,000) Admissions: 2005 Primary non-heroin opioid admission rates (per 100,000)

Primary non-heroin opioid admission rates (per 100,000) Admissions: 2007 Primary non-heroin opioid admission rates (per 100,000)

Primary non-heroin opioid admission rates (per 100,000) Admissions: 2009 Primary non-heroin opioid admission rates (per 100,000)

Marked Geographic Variation in Mortality: Estimated Age-adjusted Death Rates for Drug Poisoning by County 1999 1999 Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System; Tom Frieden Presentation at the Opioid Summit, Atlanta, April 2016 14

Marked Geographic Variation in Mortality: Estimated Age-adjusted Death Rates for Drug Poisoning by County 2002 2002 Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System; Tom Frieden Presentation at the Opioid Summit, Atlanta, April 2016 15

Marked Geographic Variation in Mortality: Estimated Age-adjusted Death Rates for Drug Poisoning by County 2005 2005 Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System; Tom Frieden Presentation at the Opioid Summit, Atlanta, April 2016 16

Marked Geographic Variation in Mortality: Estimated Age-adjusted Death Rates for Drug Poisoning by County 2008 2008 Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System; Tom Frieden Presentation at the Opioid Summit, Atlanta, April 2016 17

Marked Geographic Variation in Mortality: Estimated Age-adjusted Death Rates for Drug Poisoning by County 2011 2011 Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System; Tom Frieden Presentation at the Opioid Summit, Atlanta, April 2016 18

Marked Geographic Variation in Mortality: Estimated Age-adjusted Death Rates for Drug Poisoning by County 2014 2014 Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System; Tom Frieden Presentation at the Opioid Summit, Atlanta, April 2016 19

From Pills to Heroin Compton, New England Journal of Medicine, 2016.

The Neurobiology of Addiction 2 The Neurobiology of Addiction

DA Concentration (% Baseline) Natural Rewards Food Sex 200 200 150 150 DA Concentration (% Baseline) % of Basal DA Output 100 100 Empty 50 Box Feeding Natural rewards stimulate dopamine neurotransmission. Eating something that you enjoy or being stimulated sexually can cause dopamine levels to increase. In these graphs, dopamine is being measured inside the brains of animals. Its increase is shown in response to food or sex cues. This basic mechanism of controlled dopamine release and reuptake has been carefully shaped and calibrated by evolution to reward normal activities critical for our survival. Female Present 1 2 3 4 5 6 7 8 60 120 180 Sample Number Time (min) Adapted from: Di Chiara et al, Neuroscience, 1999 Adapted from: Fiorino and Phillips, J Neuroscience, 1997 22

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

Pleasure-Reward Pathways National Institute on Drug Abuse, www.nida.nih.gov, 2000.

3 Addiction Treatments

1st Wave: Psychoanalysis 26 Levounis, Journal of Medical Toxicology, 2016. 26

2nd Wave: Boot Camps DISASTER 27 27 27

3rd Wave: The Current Approach Mutual Help Groups (12-step) Motivational Interviewing (and CBT) Medications Family Therapy Primary Care Services Mental Health Services Aftercare Nunes, Selzer, Levounis, Davies, Substance Dependence and Co-Occurring Psychiatric Disorders, 2010. 28

What Med Staff Think Patients Think Mutual Help What Med Staff Think Patients Think Housing Outpatient Tx Medical Services Job Trusting People AA Inner Peace Community Gov’t Services Spirituality God MEDICAL STAFF Housing Gov’t Services Medical Services Outpatient Tx Job Community Trusting People Inner peace God Spirituality AA PATIENTS Inner peace God Medical Services AA Housing Spirituality Outpatient Tx Community Gov’t Services Trusting People Job Goldfarb, Am J Drug Alcohol Abuse, 1996. Levounis, Zerbo, and Aggarwal, Pocket Guide to Addiction Assessment\ and Treatment, 2017. The Neurobiology of Addiction NYU - September 15, 2014 29

Motivational Interviewing Levounis, Arnaout, and Marienfeld, Motivational Interviewing for Clinical Practice, 2017.

Medications -10 -9 -8 -7 -6 -5 -4 10 20 30 40 50 60 70 80 90 100 % Efficacy Log Dose of Opioid Full Agonist (Methadone) Partial Agonist (Buprenorphine) Antagonist (Naltrexone) Renner and Levounis, Office-Based Buprenorphine Treatment of Opioid Dependence, APA Publishing, 2011.

4 New Directions

4th Wave: Mindfulness “Between stimulus and response there is a space. In that space is our power to choose our response. In our response lie our growth and our freedom.” Viktor E. Frankl Frankl V, Man’s Search for Meaning, 1959. Zerbo, Schlechter, Desai, and Levounis, Becoming Mindful, 2017. 33

And Back to Psychodynamics… *** Ref % reporting any substance use disorders *** * * Ref Women Men *p<0.05, ***p<.001 based on logistic regression analysis adjusted for race, age, educational level, personal income, employment status, relationship status, health insurance status, geographic location, MSA, age at alcohol onset, and family history of AOD problems. Reference group was “heterosexual” group. McCabe SE, Addiction, 2009; courtesy of Sean McCabe, PhD. Levounis, Drescher, and Barber, The LGBT Casebook, 2012.

5 Conclusions

Addiction hijacks the pleasure/reward pathways of the brain and weakens the frontal lobes. Mutual help, motivational interviewing, and partial agonists are the foundations of addiction treatment in 2017.

Thank you