Addictions and the Brain

• La Hacienda Treatment Center • American Society of Addiction Medicine • NtiNationa lIl Ins titttitute of fD Drug Ab use

• A primary, progressive biochemical, psychosocial, genetically transmitted chronic disease of relapse who’s hallmarks are denial, loss of control and unmanageability.

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. © 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

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

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

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

Alcoh o 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.

a. Chemical of choice b. Related drugs c. Tobacco d. Life long relapse pathway

a. Historyyy of discovery b. Three month limit for relapse

I. Antabuse II. Campral III. ReVia IV. Vivitrol V. Off label

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