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Addictions and the Brain

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Addictions and the Brain 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. Withdrawal 2. Tolerance 3. The substance is taken in larger amounts or over a longer period than was intended. 4. There is a persistent desire or unsuccessful efforts to cut down or control substance use. 5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects. 6. Important social, occupational, or recreational activities are given up or reduced because of the substance use. 7. 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 Natural Rewards Elevate Dopamine Levels FOOD SEX 200 200 NAc shell 150 150 Copulation Frequency Copulation 100 100 15 Empty 10 50 Box Feeding % of Basal DA Output Basal of DA % 5 DA Concentration Concentration (% Baseline) DA 0 0 0 60 120 180 ScrScr Scr Scr BasFemale 1 Present Female 2 Present Time (min) Sample 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Number Mounts Intromissions Ejaculations Source: Di Chiara et al. Source: Fiorino and Phillips Effects of Drugs on Dopamine Levels Accumbens COCAINE 1100 AMPHETAMINE Accumbens 1000 400 900 800 DA DA 300 DOPAC 700 DOPAC HVA 600 HVA 500 200 400 % ofRelease Basal % 300 % ofRelease Basal % 200 100 100 0 0 1 2 3 4 5 hr 0 0 1 2 3 4 5 hr Time After Amphetamine Time After Cocaine 250 NICOTINE Accumbens MORPHINE 250 Dose (mg/kg) 200 Accumbens 200 0.5 Caudate 1.0 150 2.5 150 10 100 100 % ofRelease Basal % % ofRelease Basal % 0 0 1 2 3 hr 0 0 1 2 3 4 5hr Time After Nicotine Time After Morphine 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 Inferior © 2012 La Hacienda Treatment Center. All rights reserved. 10 9/18/2012 Dopamine Transporters in Methamphetamine Abusers 2.4 2.2 2.0 1.8 Normal Control 1.6 1.4 (Bmax/Kd) 1.2 Dopamine Transporters Dopamine 1.0 Normal Meth Controls Abusers Methamphetamine Abuser 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 Transporters in Methamphetamine Abusers Motor Task 2.0 1.8 Loss of dopamine transporters 1.6 in the meth abusers may result 1.4 in slowing of motor reactions. 1.2 1.0 7 8 9 10 11 12 13 Time Gait (seconds) Bmax/Kd 2.0 Dopamine Transporter Dopamine Memory Task 1.8 1.6 Loss of dopamine transporters 1.4 in the meth abusers may result in memory impairment. 1.2 1.0 16 14 12 10 8 6 4 Delayed Recall (words remembered) BNL/UCLA/SUNY NIDA, ONDCP, DOE Dopamine D2 Receptors in Addiction Control Experimental groups 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 Treatment © 2012 La Hacienda Treatment Center. All rights reserved. 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. Chemical of choice b. Related drugs c. Tobacco d. 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. Boredom b. Hunger c. Anger/emotions d. Loneliness e. Tiredness Relapse Prevention Medications I. Antabuse II. Campral III. ReVia IV. Vivitrol V. Off label © 2012 La Hacienda Treatment Center. All rights reserved. 20 9/18/2012 Antabuse a. Mechanism of action b. Dosing c. Side Effects d. Efficacy Campral a. Mechanism of action b. Dosing c. Side Effects d. Efficacy © 2012 La Hacienda Treatment Center. All rights reserved. 21 9/18/2012 ReVia a. Mechanism of action b. Dosing c. Side Effects d. Efficacy Vivitrol a. Mechanism of action b. Dosing c. Side Effects d. 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 Cabergoline Bupropion Lofexidine Disulfiram (Antabuse) Reserpine Selegiline © 2012 La Hacienda Treatment Center. All rights reserved. 23 9/18/2012 Methamphetamine Addiction Pharmacotherapies Opiate Medication Development Projects inin ClinicalClinical TrialsTrials Phase I Phase II Phase I Phase II Phase III Bupropion Amlodipine Bupropion Cycloserine Bupropion Buprenorphine Disulfiram Baclofen Depot Naltrexone Buspirone Buprenorphine/Naloxone Lobeline Desipramine Enadoline Clonidine Lofexidine Reserpine Fluoxetine Lamotrigine Lofexidine Selegiline Flupenthixol Gabapentin Tramadol Memantine IsradipineIsradipine Methylphenidate Olanzapine Midazolam/N20/N20 Ondansetron Naloxone Pemoline Naltrexone Selegiline Nefazedone Venlafaxine Cocaine Medication Development Projects Phase I Phase II Screen Phase II Phase III Amantadine Disulfiram Butorphanol BP 4897 Amlodipine Selegiline TS DAS 431 Cocaine Vaccine Baclofen Selegiline TS Dextromethorphan Bupropion GBR 12909 Butorphanol Metyrapone IsradipineIsradipine Cabergoline Captopril Modafinil Lamotrigine Captopril Memantine Clopidogrel NS 2359 Memantine Disulfiram Tolcapone Ondansetron Gabapentin Sibutramine Memantine Methylphenidate Naltrexone Oxazepam Pemoline Propranolol Reserpine Risperidone SertralineSertraline Taurine Tiagabine Venlafaxine 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 Mood, Anxiety, ADD Disorder 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 Just gotta be me! Are you talking to me? Gotta Dance! - Fails to finish tasks 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
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