9/18/2012 Addictions and the Brain TAAP Conference September 14, 2012 Acknowledgements • La Hacienda Treatment Center • American Society of Addiction Medicine • National Institute of Drug Abuse © 2012 La Hacienda Treatment Center. All rights reserved. 1 9/18/2012 Definition • A primary, progressive biochemical, psychosocial, genetically transmitted chronic disease of relapse who’s hallmarks are denial, loss of control and unmanageability. DSM IV Criteria for dependency: At least 3 of the 7 below 1. 2. 3. 4. 5. 6. 7. Withdrawal Tolerance The substance is taken in larger amounts or over a longer period than was intended. There is a persistent desire or unsuccessful efforts to cut down or control substance use. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects. Important social, occupational, or recreational activities are given up or reduced because of the substance use. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance. © 2012 La Hacienda Treatment Center. All rights reserved. 2 9/18/2012 Dispute between behavior and disease Present understanding of the Hypothalamus location of the disease hypothesis. © 2012 La Hacienda Treatment Center. All rights reserved. 3 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 4 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 5 9/18/2012 Dispute regarding behavior versus disease © 2012 La Hacienda Treatment Center. All rights reserved. 6 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 7 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 8 9/18/2012 200 % of Basal DA Output NAc shell 150 100 Empty 50 Box Feeding 200 150 100 15 10 5 0 0 0 60 120 ScrScr BasFemale 1 Present 180 Time (min) Scr Copulation Frequency DA Concentration (% Baseline) Natural Rewards Elevate Dopamine Levels FOOD SEX Scr Female 2 Present Sample 1 2 3 4 5 6 7 8 Number 9 10 11 12 13 14 15 16 17 Mounts Intromissions Ejaculations Source: Di Chiara et al. Source: Fiorino and Phillips Accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 DA DOPAC HVA 1 2 3 4 Time After Amphetamine NICOTINE 200 Accumbens Caudate 100 0 0 1 2 3 hr Time After Nicotine Accumbens COCAINE DA DOPAC HVA 300 200 100 0 5 hr 250 150 % of Basal Release 400 0 % of Basal Release AMPHETAMINE % of Basal Release % of Basal Release Effects of Drugs on Dopamine Levels 250 0 1 2 3 4 Time After Cocaine Accumbens 5 hr MORPHINE Dose (mg/kg) 0.5 1.0 2.5 10 200 150 100 0 0 1 2 3 4 Time After Morphine 5hr Source: Di Chiara and Imperato © 2012 La Hacienda Treatment Center. All rights reserved. 9 9/18/2012 Striatal FDOPA Activity Pre-Amphetamine/Control Post-Chronic Amphetamine (10 days) 4 weeks 6 months 1 year 2 years Superior © 2012 La Hacienda Treatment Center. All rights reserved. Inferior 10 9/18/2012 Dopamine Transporters in Methamphetamine Abusers Normal Control Dopamine Transporters (Bmax/Kd) 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 Normal Controls Methamphetamine Abuser Meth Abusers p < 0.0002 Methamphetamine abusers have significant reductions in dopamine transporters. BNL - UCLA - SUNY NIDA - ONDCP - DOE © 2012 La Hacienda Treatment Center. All rights reserved. 11 9/18/2012 Dopamine Transporter Bmax/Kd Dopamine Transporters in Methamphetamine Abusers Motor Task 2.0 1.8 1.6 1.4 1.2 1.07 Loss of dopamine transporters in the meth abusers may result in slowing of motor reactions. 8 9 10 11 12 13 Time Gait (seconds) 2.0 1.8 1.6 1.4 1.2 1.0 16 14 12 10 8 6 Memory Task Loss of dopamine transporters in the meth abusers may result in memory impairment. 4 Delayed Recall (words remembered) BNL/UCLA/SUNY NIDA, ONDCP, DOE Dopamine D2 Receptors in Addiction Control groups Experimental groups Cocaine Meth Alcohol Food © 2012 La Hacienda Treatment Center. All rights reserved. 12 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 13 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 14 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 15 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 16 9/18/2012 Challenge: Normal Drug Use Addiction © 2012 La Hacienda Treatment Center. All rights reserved. Treatment 17 9/18/2012 Three Major Relapse Pathways I. Cross Addicting Drugs II. People/Place/Things III. B.H.A.L.T. © 2012 La Hacienda Treatment Center. All rights reserved. 18 9/18/2012 Cross Addicting Drugs a. b. c. d. Chemical of choice Related drugs Tobacco Life long relapse pathway People/Place/Things a. History of discovery b. Three month limit for relapse © 2012 La Hacienda Treatment Center. All rights reserved. 19 9/18/2012 B.H.A.L.T. a. b. c. d. e. Boredom Hunger Anger/emotions Loneliness Tiredness Relapse Prevention Medications I. II. III. IV. V. © 2012 La Hacienda Treatment Center. All rights reserved. Antabuse Campral ReVia Vivitrol Off label 20 9/18/2012 Antabuse a. b. c. d. Mechanism of action Dosing Side Effects Efficacy Campral a. b. c. d. Mechanism of action Dosing Side Effects Efficacy © 2012 La Hacienda Treatment Center. All rights reserved. 21 9/18/2012 ReVia a. b. c. d. Mechanism of action Dosing Side Effects Efficacy Vivitrol a. b. c. d. Mechanism of action Dosing Side Effects Efficacy © 2012 La Hacienda Treatment Center. All rights reserved. 22 9/18/2012 Off label Phase 3 Clinical Trials On A Number of Promising Drugs Cocaine Methamphetamine Opiates Bupropion Lofexidine Cabergoline Disulfiram (Antabuse) Reserpine Selegiline © 2012 La Hacienda Treatment Center. All rights reserved. 23 9/18/2012 Methamphetamine Addiction Pharmacotherapies in Clinical Trials Phase I Bupropion Disulfiram Lobeline Reserpine Selegiline Phase II Amlodipine Baclofen Desipramine Fluoxetine Flupenthixol Gabapentin Isradipine Olanzapine Ondansetron Pemoline Selegiline Venlafaxine Opiate Medication Development Projects Phase I Phase II Phase III Cycloserine Depot Naltrexone Enadoline Lamotrigine Tramadol Bupropion Buspirone Clonidine Lofexidine Memantine Methylphenidate Midazolam/N20 Naloxone Naltrexone Nefazedone Buprenorphine Buprenorphine/Naloxone Lofexidine Cocaine Medication Development Projects Phase I Phase II Screen Butorphanol DAS 431 GBR 12909 Metyrapone Modafinil NS 2359 Tolcapone BP 4897 Cocaine Vaccine Dextromethorphan Isradipine Lamotrigine Memantine Ondansetron Sibutramine Phase II Phase III Amantadine Amantadine Amlodipine Amlodipine Baclofen Baclofen Bupropion Bupropion Butorphanol Butorphanol Cabergoline Cabergoline Captopril Captopril Clopidogrel Clopidogrel Disulfiram Disulfiram Gabapentin Gabapentin Memantine Memantine Methylphenidate Methylphenidate Naltrexone Naltrexone Oxazepam Oxazepam Pemoline Pemoline Propranolol Propranolol Reserpine Reserpine Risperidone Risperidone Sertraline Sertraline Taurine Taurine Tiagabine Tiagabine Venlafaxine Venlafaxine Disulfiram Selegiline TS Dual Diagnosis 1. Prevalence 2. Testing 3. Treatment © 2012 La Hacienda Treatment Center. All rights reserved. 24 9/18/2012 Co-Occurring Disorders Substance Use Disorder Mood, Anxiety, ADD Psychotic 37% of alcohol dependent  another disorder 53% of drug dependent  another disorder Etiology Mental Illness Substance Use –  Symptoms –  Social skills –  Medication side effects © 2012 La Hacienda Treatment Center. All rights reserved. 25 9/18/2012 Etiology Substance Use Mental Illness – Dependence ↑ psychosis, depression, anxiety – Withdrawal ↑ depression and anxiety – ? Shared genetics Anxiety • Generalized – Pervasive • Panic – Sudden onset and resolution • Social (9% same as general population) – Associated with social situations • PTSD – Hypervigilence resulting from trauma • OCD – Germs, organizing, checking and re-checking © 2012 La Hacienda Treatment Center. All rights reserved. 26 9/18/2012 Panic Social PTSD Generalized OCD Normal Emotional States Withdrawal from alcohol, benzodiazepines, opiates, and other sedatives mimics anxious state Treatment – Anxiety • Behavioral – Therapy as good as medications in most research trials – Hypnosis, Biofeedback, Exercise – The Anxiety Cure – Author Dupont • Medications – SSRIs (Prozac, Paxil, Lexapro, Celexa, Zoloft) – SNRIs (Cymbalta, Effexor, Pristiq) – Buspar – Short- term: Inderal, Vistaril, Neurontin – Trazodone © 2012 La Hacienda Treatment Center. All rights reserved. 27 9/18/2012 Mood • Depression – Major Depression – Dysthymia • Mania – Mania – Hypomania • Bipolar – I – Manic Episode(s) with or without Depressive Episode(s) – II – Depressive Episodes(s) with Hypomania – Cyclothymia – Hypomania and dysthymic episodes Mania hypomania Normal Emotional States dysthymia Major Depression Withdrawal can mimic mania or depression © 2012 La Hacienda Treatment Center. All rights reserved. 28 9/18/2012 Treatment - Mood • Medications – SSRIs, SNRIs – Wellbutrin (Bupropion) – Mood Stabilizers/Augmenters – Lithium, Depakote, Risperidone, Seroquel, Topamax, Lamictal, Trileptal, Abilify, Geodon, Zyprexa • Behavioral – Therapy = medications for depression – Exercise, diet, sunlight useful ADD/ADHD • 25 fold h in Adderall use last decade • USA = 80 % of Ritalin used worldwide • No study shown long term use stimulants in adults is good © 2012 La Hacienda Treatment Center. All rights reserved. 29 9/18/2012 Symptoms - Not listening - Fails to finish tasks Just gotta be me! Are you talking to me? Gotta Dance! I’m molting…….. - Difficulty organizing - Loses things - Easily distracted Other Causes • • • • Anxiety Mania Withdrawal Learning Disorders Treating for ADD first can lead to worsening of above © 2012 La Hacienda Treatment Center. All rights reserved. 30 9/18/2012 Treatment - ADD • Therapy and treatment of any underlying learning disability • Exercise • Atypical stimulants – Strattera (amoxetine) • Guanfacine (Tenex, Intuniv) • SNRIs – Effexor, Prestiq • Wellbutrin (Bupropion) Personality Disorders • Disorders? • Phases? • Artifacts of Addiction? “so you are anti-social, histrionic, borderline, and narcissistic but otherwise well.” © 2012 La Hacienda Treatment Center. All rights reserved. 31 9/18/2012 PERSONALITY DISORDERS • Totality of Emotional + Behavioral Traits • Onset Teens • Enduring, Inflexible, Consistent, Maladaptive Causes Significant Impairment and/or Distress Personality Characteristics Cluster A – Eccentric or Odd Paranoid Suspicious, Jealous, but not Psychotic or Unlawful Schizoid Unemotional, Cold, Indifferent Schizotypal Odd /Magical, not Paranoid Cluster B – Dramatic, Emotional, or Erratic ASPD Borderline Histrionic Narcissistic not Unlawful Aggressive, Unlawful, Impulsive Unstable, Chaotic, Impulsive Dramatic, Seductive but not Unlawful Self-Centered, Entitled, Lacks Empathy, © 2012 La Hacienda Treatment Center. All rights reserved. but 32 9/18/2012 Personality Characteristics Cluster C – Anxious or Fearful Avoidant Needs people but Fears Relationships Dependent Fears Needs Relationships, Indecisive, Abandonment ObsessiveCompulsive Rigid, Perfectionist + Inefficient PassiveNegative Attitudes with Passive Aggressive Resistance to Demands Summary • Very common to have both a substance use disorder and another disorder • Even more common to feel like you have one when using or withdrawing • The six month challenge • The twelve month reward © 2012 La Hacienda Treatment Center. All rights reserved. 33 9/18/2012 Spiritual Component of Recovery © 2012 La Hacienda Treatment Center. All rights reserved. 34 9/18/2012 Dr. Daniel Boone La Hacienda Treatment Center 800-749-6160 [email protected] © 2012 La Hacienda Treatment Center. All rights reserved. 35