Chemical Dependency a New Paradigm

1. Chemical Dependencya New Paradigm Richard L. Hinchman, M.D., FACOG, FASAM

2. Your Brain on Drugs in the 1980’s

3. What the mind does not know, the eyes cannot see

4. If drugs and alcohol were the problem ……

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11. Animal Models • Alcohol (P) Preferring Mice • Alcohol (NP) Non-preferring Mice

12. DA measurement in NA

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15. Positron Emission Tomography (PET)

16. Human Studies • PET scans of sons of alcoholic fathers • Sons were naïve to alcohol • 40% had lower Dopamine (DA) levels when compared to controls

17. Quick Review • Dependence is a Primary Disease • 40% to 60% genetic predisposition • Not located in judgment area of brain • Located in the mid-brain (survival) • Mid-brain controls the judgment area • DA Deficiency is underlying pathology • Treatment must maintain DA levels at the set point for survival

18. Abuse vs. Dependence • Drug/Alcohol Abuse is a preventable behavior under the control of the PFC (judgment) • Normal DA levels in mid-brain • Drug/Alcohol Dependence is a treatable primary disease located in the mid-brain, (survival). • DA deficiency in mid-brain

19. Alcohol Abusers • 5-year follow-up of ~1,300 men & women • All met DSM-IV criteria for Abuse only • 5 years later only 3% met DSM-IV criteria for Dependence Schuckit, M.A. et. al., Five year clinical course associated with DSM-IV alcohol abuse ……Am. J. Pshchiat. 158: 1084-1090

20. 33.7% of all alcoholics who met DSM-IV criteria for Dependence… Did not previously meet DSM-IV criteria for Abuse NESARC 2001-02 study

21. Genetic Predisposition • 10% risk with no family history….. • 40% risk with one parent….. • 90+% risk with both parents….

22. Chronic ETOH Consumption • Chronic use of alcohol changes the genetic makeup of the neuron • Changes the structure of the receptor proteins, (D2 receptors) • Fewer D2 receptors for DA to bind to • Increased tolerance since more alcohol is required to get the same effect

23. The earlier a young person drinks ETOH, the more likely he/she will develop a clinically defined alcohol disorder later in life Young people who begin drinking before age 15 are 4x more likely to develop alcoholism than those who wait until they are 21 to drink NIAAA 2000

24. For each year an adolescent delays use of alcohol, he/she decreases the odds of lifelong dependence by 14%, and lifelong abuse by 8% NIAAA January 2000

25. When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Deborah Yurgelon-Todd 2000.

26. Social Structure & DA Levels • Altering social hierarchy in monkeys • PET scan measurements of DA levels • Higher social status had higher DA levels • Manipulation of the social hierarchy causing the higher levels monkeys to be moved to the lower levels…. • DA levels decreased in their NAc

27. Screening for At-Risk Drinking • How many drinks containing ETOH do you consume per week? Per occasion? • Men: >14 drinks per week > 4 drinks per occasion • Women: > 7 drinks per week > 3 drinks per occasion

28. C.A.G.E. C: Have you ever tried to Cut down on your drinking? A: Do you become Annoyed when people talk to you about your drinking? G: Do you ever feel Guilty about your drinking? E: Have you ever had an “Eye Opener” (a drink in the morning) • Positive screen if yes to 2 or more

29. C.R.A.F.F.T.Adolescent Screening C: Have you ever ridden in a Car driven by someone (including yourself) who was “high” or had been using alcohol or drugs? R: Do you ever use alcohol or drugs to Relax, feel better about yourself, or to fit in? A: Do you ever use alcohol or drugs while you are Alone?

30. C.R.A.F.F.T.Adolescent Screening F:Do you ever Forget things you did while using drugs or alcohol? F:Do your Family or Friends ever talk to you about your drinking or drug use? T:Have you gotten into Trouble while you were using alcohol or drugs? “Yes” to 2 or more is predictive of a Substance Use Disorder

31. How Does the Alcoholic Define Alcoholism? • The average alcoholic has a family, home, job & responsibility • Only 3% of alcoholics are the stereotype “skid row bums” • The alcoholic will continue to change his/her definition…

32. DSM-IV Substance Dependence >/= 3 of the following in a 12 month period • Tolerance • Withdrawal • Using larger amounts than intended • Persistent efforts to cut down or control use • Great deal of time spent getting the substance, taking it, & recovering • Important activities given up for using • Continued use despite psychological or physical problems caused by using the substance

34. Level I Individual counselling Level II.1 Intensive Outpatient (IOP) Level II.5 Partial Hospitalization Level III.1-III.5 Non-hospital Residential Level III.7 Inpatient Medically Monitored Level IV General Hospital with ICU Aftercare: Facilitated meetings to help with reentry to family, work & society (6-12 months)

35. Twelve Step Recovery Robert L. Dupont, M.D. • 1st president of NIDA • 2nd U.S. Drug Czar • The Selfish Brain: learning from addiction • “The secret weapon in the war on drugs is the 12-Step program” • “12-Step programs are the key to long-term recovery” • “12-Step recovery is THE ONLY THING THAT WORKS”

36. Georgia Physician’s Study • At least five 12-Step meetings per week • Weekly Caduceus meetings • 77% success at 7 years • 76% of relapsers remained sober after 2 years with additional treatment

37. Extended Abstinence is Predictive of Sustained Recovery After 5 years – if you are sober, you probably will stay that way. It takes a year of abstinence before less than half relapse Dennis et al, Eval Rev, 2007

38. Incubation of Relapse Propensity Over Time • The longer an individual remains in their old “using” environment immediately after treatment, the greater the risk of relapse • This may be measured in days

39. Relapse Prevention

40. 3 Different Classes of Relapse • Stress mediated: (POMC) • “Cue” mediated (“euphoric recall”) • Drug mediated: (VTA-to-NAc) • Cross Addiction • Opiate Rx for legitimate pain

41. Stress and Relapse • Pro-opio-melanocortic (POMC) • MSH + ACTH + beta-endorphin • Increases Dopamine levels in NAc • CRF antagonists significantly reduced alcohol consumption in alcohol (P) mice

43. Cross-Addiction • Mouthwash containing alcohol • Cough syrups containing alcohol • Benadryl • O’Doule’s (non-alcoholic beer) • Prescription Sabotage

44. Prescription Sabotage • Propoxyphene (methadone-related) • Talwin (opioid agonist-antagonist) • Ultram (central opioid agonist) • Provigil (narcolepsy, sleep apnea) • Lyrica

45. Opiates and Pain • Opiates bind to Mu receptors • Inhibit the Mu receptors • Decrease in adenyl cyclase activity • Decrease in cyclic-AMP • Increase in K+ efflux • Decrease in Ca++ influx • Hyperpolarizationof the pain nerve fibers in the ascending & descending pathways resulting in a reduction of pain Prolonged use of a short acting opiate reverses this cascade resulting in increased pain

47. Prolonged Opiate UseDenmark Epidemiological Study Chronic opiate use for non-cancer pain relief Denmark has the highest per capita use of opioids in the world Eriksen, Bruera, et.al. Critical issues on opioids in chronic non-cancer pain. An epidemiological study. Pain 2006; 125: 172-179

48. Patients reported: • Significantly more pain • Poorer self-rated health • Lower quality of life • Lower levels of physical activitiy • Lower levels of employment • Higher levels of health care utilization