The Neurobiological Model of Addiction

1. The Neurobiological Model of Addiction Carlton Erickson, Ph.D. Director, Addiction Science Research and Education Center University of Texas at Austin, USA APIA-Singapore, 2004

2. There once was a disease….. • • people who had it were disgraced • • sufferers felt isolated and alone • • sufferers had permanent psychological damage • • the disease had insufficient funding for treatment • • there was poor understanding about the cause

3. That disease was… • POLIO • (50 years ago) • If we had continued to onlytreat polio, • today we would have • computerized iron lungs! • But now polio is (almost) only a memory

4. Today we face a challenge….. • • we’re trying hard to help people with drug problems, but we can’t help them all • • why? • - we hang on to outmoded beliefs • - we don’t have all the answers • - to policy makers, we appear to not know • what we’re doing

5. S.P.A.M. is killing us! • • Stigma • • Prejudice • • Anger • • Misunderstanding • This has led to discrimination against addicts and inadequate $$ for treatment, education, research…

6. Look at all the addictions we deal with! • • alcohol, heroin, cocaine, nicotine, marijuana, Rx drugs, club drugs… • • gambling, sex, internet, work, food • • ARE WE TAKING ON TOO MUCH?

7. And then these….. • • cell phone • sugar • • Thomas Kincaid • A.A. meetings • • television • shoes • • Ben & Jerry’s • cars • • exercise • Disneyland • • “other people” • chocolate

8. We must clarify the words “addiction” and “alcoholism”, both of which have lost their scientific and clinical value

9. According to DSM-IV: • • substance (drug, chemical) abuse - overuse of drugs in cases where people are making poor judgments about drug use: (“a problem to solve”) • • not a minor problem, since drug abusers produce a majoreconomic impact on society

10. But this is the disease* • • substance (drug, chemical) dependence - impaired control over drug use, probably caused by a dysfunction in the brain’s “pleasure pathway” (“a disease to conquer”) • • this requires twelve-step or other programs (treatments) • • dependence = addiction; alcohol abuse • is not “alcoholism” • * Based on the Diagnostic and Statistical Manual-IV-TR • (DSM-IV-TR)

11. RESEARCH VALIDITY ESTIMATE (RVE) (A Thoughtful Appraisal of High-Quality Scientific Research) High RVE • many large, well-controlled studies • replicable results • much peer-reviewed, published literature Low RVE • few replicable studies • highly speculative results • little peer-reviewed, published literature 100 - 0

12. Does “abuse” lead to “dependence”? • 5-year follow-up of ~1300 men and women: • • 3% of abusers met criteria for depend. • • DSM diagnosis of depend.: chronic disorder w/ relatively severe course; DSM abuse - milder disorder that does not usuallyprogress to dependence • Schuckit et al., 2001 40

13. Dependence as a disease

14. Early vs. Late Onset • • It “looks” like many people evolve from abuse to dependence • • Some people become dependent during the first year of use • • Anecdotal - some people become “instantly dependent” • • Some abusers never become dependent

15. Risk of Dependence • • data from National Comorbidity Survey • (n= 8,100), ages 15-54 y-o (both genders) • • dep occurrence in 10 years: cocaine, 15-16% • alcohol, 12-13%; marijuana, 8% • • cocaine: 5-6% dep in 1st year of use; 80% • were dependent within 3 years • Wagner & Anthony, 2002 30

16. Other reports…. • Institute of Medicine- users • who become dependent: • • nicotine - 32% • • heroin - 23% • • cocaine - 17% • • alcohol - 15% • • marijuana - 9% 40

17. The Mesolimbic Dopamine System*Model of Impaired Control___________________* a.k.a. Medial Forebrain Bundle (MFB)

18. “Dependence” Brain Areas • • mesolimbic dopamine system • • “key elements of a basal forebrain macrostructure” • extended amygdala (Koob) • - central nucleus of amygdala • - bed nucleus of the stria terminalis • - transition zone, medial (shell) of NAc 60

20. Medial Forebrain Bundle • • ventral tegmental area (VTA) • • (lateral) hypothalamus (LH) • • nucleus accumbens (NAcc) • • frontal cortex (FC) - key portions • - prefrontal cortex (PFC) • - orbitofrontal cortex (OFC) 95

21. The disorder is involved with neurotransmitter problems in the dependence brain areas.

22. Neurotransmitters Involved in Dependence • Probable functional dysregulation (MFB): • • Dopamine (DA) • • Serotonin (SER) • • Endorphins (END) • • Gamma-aminobutyric acid (GABA) • • Glutamate (GLU) • • Acetylcholine (ACh) 70

23. Drugs Associated wth Neurotransmitters • Why do people have “drugs of choice”? • • Dopamine - amphets, cocaine, ETOH • • Serotonin - LSD, ETOH • • Endorphins - opioids, ETOH • • GABA - benzos, ETOH • • Glutamate -ETOH • • Acetylcholine - nicotine, ETOH • (Marijuana?) (THIQs are no longer popular.) 70

24. Is There a “Switch” to Turn on the Disease? • • GABA-A receptors in the VTA • • Two states: • - DA-independent (opiate-naive) • - DA (opiate-dependent, opiate-WD) • • opiate exposure and WD: the VTA GABA-A receptor “switches” • (VTA=ventral tegmental area, DA=dopamine, WD=withdrawal) • Laviolette et al., 2004 20

25. A Brain Chemistry Disease! • • addicting drugs seem to “match” the transmitter system that is not normal • • cases range from mild to severe • • this is a chronic medical illness • • methadone and nicotine maintenance is evidence that some people require a chemical to overcome the non-normal transmitter system 80

26. Remember the Best Academic Website in the World! www.utexas.edu/research/asrec