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Addictions and the Brain Addictions and the Brain © 2008 La Hacienda Treatment Center. All rights reserved. Acknowledgements • La Hacienda Treatment Center • American Society of Addiction Medicine • NtiNationa lIl Ins titttitute o fDf Drug Abuse © 2008 La Hacienda Treatment Center. All rights reserved. Definition • A primary, progressive biochemical, psychosocial, genetically transmitted chronic disease of relapse who’s hallmarks are denial, loss of control and unmanageability. © 2008 La Hacienda Treatment Center. All rights reserved. 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. © 2008 La Hacienda Treatment Center. All rights reserved. Dispute between behavior and disease © 2008 La Hacienda Treatment Center. All rights reserved. Present understanding of the Hypothalamus location of the disease hypothesis. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. Dispute regarding behavior versus disease © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. Natural Rewards Elevate Dopamine Levels FOOD SEX 200 200 ne)ne) NAc shell iiii 150 150 utpututput n (% (% (% n n BaselBasel OOOO ooo o Copulation 100 100 15 Empty 10 oncentrationcentrati F f Basal DA f Basal DA f Basal DA C CCC 50 requency ooo o Box Feeding % % 5 DA DA DA 0 0 006060 120 180 ScrScrScrScr Scr Scr BasFemale 1 Present Female 2 Present Time (min) Sample 1122334455667788 991010 11 12 13 14 15 16 17 Number Mounts Intromissions Ejaculations Source: Di Chiara et al. Source: Fiorino and Phillips © 2008 La Hacienda Treatment Center. All rights reserved. Effects of Drugs on Dopamine Levels Accumbens COCAINE 1100 AMPHETAMINE Accumbens 1000 400 900 800 DA DA 300 eleaseelease Release Release DOPAC llll 700 DOPAC RRRR HVA 600 HVA 500 200 400 % of Basa of Basa % % 300 200 of Basal of Basal % % 100 100 0 001122334455 hr 0 001122334455 hr Time After Amphetamine Time After Cocaine 250 NICOTINE 250 Accumbens MORPHINE Dose (mg/kg) 200 Accumbens 200 0.5 Caudate 1.0 l Releasel Release ReleaseRelease aaaa 150 252.5 150 10 100 100 % of% of Bas Bas % of Basal of Basal % % 0 00112233 hr 0 00112233445hr5hr Time After Nicotine Time After Morphine © 2008 La Hacienda Treatment Center. Source: Di Chiara and Imperato All rights reserved. Striatal FDOPA Activity Pre-Ahti/CtlAmphetamine/Control Post-Chronic Amphetamine (10 days) 4 weeks 6 months 1 year 2 years © 2008 La Hacienda Treatment Center. Superior Inferior All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. Dopamine Transporters in Methamphetamine Abusers 2.4 2.2 rs ee 2.0 1.8 /Kd) ansport rr Normal Control xx 161.6 1.4 (Bma amine T 1.2 pp Do 1.0 Normal Meth Controls Abusers Methamphetamine Abuser p < 0.0002 Methamphetamine abusers have significant reductions in dopamine transporters. BNL --UCLAUCLA - SUNY © 2008 La Hacienda Treatment Center. All rights reserved. NIDA - ONDCP - DOE 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. sporter 1.2 nn 1.07 8 9 10 11 12 13 Time Gait (seconds) mine Tra Bmax/Kd aa 2.0 Dop Memory Task 1.8 1.6 Loss of dopamine transporters 1.4 ithin the meth thb abusers may resu lt 1.2 in memory impairment. 1.0 16 14 12 10 8 6 4 Delayed Recall (words remembered) BNL/UCLA/SUNY © 2008 La Hacienda Treatment Center. All rights reserved. NIDA, ONDCP, DOE Dopamine D2 Receptors in Addiction Control Experimental groups groups Cocaine Meth Alco ho l Food © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. Cha llenge: Normal Drug Use Addiction Treatment © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. Three Major Relapse Pathways I. Cross Addicting Drugs II. Pl/Pl/ThiPeople/Place/Things III. B.H.A.L.T. © 2008 La Hacienda Treatment Center. All rights reserved. Cross Addicting Drugs a. Chemical of choice b. Related drugs c. Tobacco d. Life long relapse pathway © 2008 La Hacienda Treatment Center. All rights reserved. People/Place/Things a. Historyyy of discovery b. Three month limit for relapse © 2008 La Hacienda Treatment Center. All rights reserved. BHALTB.H.A.L.T. a. Boredom b. Hunger c. Anger/emotions d. LliLoneliness e. Tiredness © 2008 La Hacienda Treatment Center. All rights reserved. Relapse Prevention Medications I. Antabuse II. Campral III. ReVia IV. Vivitrol V. Off label © 2008 La Hacienda Treatment Center. All rights reserved. Antabuse a. Mechanism of action b. DiDosing c. Side Effects d. Efficacy © 2008 La Hacienda Treatment Center. All rights reserved. Campral a. Mechanism of action b. DiDosing c. Side Effects d. Efficacy © 2008 La Hacienda Treatment Center. All rights reserved. ReVia a. Mechanism of action b. Dosing c. Side Effects d. Efficacy © 2008 La Hacienda Treatment Center. All rights reserved. Vivitrol a. Mechanism of action b. DiDosing c. Side Effects d. Efficacy © 2008 La Hacienda Treatment Center. All rights reserved. Off label © 2008 La Hacienda Treatment Center. All rights reserved. Phase 3 Clinical Trials On A Number of Promising Drugs Cocaine Methamphetamine Opiates Cabergoline Bupropion Lofexidine Disulfira m ( Antabuse) Reserpine Se legili iline © 2008 La Hacienda Treatment Center. All rights reserved. Methamphetamine Addiction Pharmacotherapies Opiate Medication Development Projects inin Clinical 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 MemantineMemantine Isradipine Methylphenidate Olanzapine Midazolam/N20 Ondansetron Naloxone Pemoline Naltrexone Selegiline Nefazedone VlfiVenllaffaxiinene 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 LamotrigineLtiiLamotrigine Captopril Memantine Clopidogrel NS 2359 Memantine Disulfiram Tolcapone Ondansetron Gabapentin Sibutramine Memantine Methylphenidate Naltrexone Oxazepam Pemoline PropranololPllPropranolol Reserpine Risperidone Sertraline Taurine Tiagabine Venlafaxine © 2008 La Hacienda Treatment Center. All rights reserved. Dual Diagnosis 1. Prevalence 2. Testing 3. Treatment © 2008 La Hacienda Treatment Center. All rights reserved. © 2008 La Hacienda Treatment Center. All rights reserved. Spiritual Component of Recovery © 2008 La Hacienda Treatment Center. All rights reserved. Dr. Daniel Boone La Hacienda Treatment Center 800-749-6160 [email protected] www.lahacienda.com © 2008 La Hacienda Treatment Center. All rights reserved..
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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.
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