2. No financial ties to any drug company Not a consultant, speaker, etc. No individual stocks in drug companies Disclosures

3. 1. Evidence that AA works 2. A theory of why AA works 3. A brief comment on the debate about AA and MAT 4. A few slides on the future of drug treatment This talk will include:

5. A Cochrane review of studies on alcohol treatment conducted between 1966 and 2005 found: No experimental studies unequivocally demonstrated the effectiveness of AA for reducing alcohol dependence or problems. The AA controversy

6. Journalism in the Public Interest “Twelve Steps to Danger: How Alcoholics Anonymous Can Be a Playground for Violence-Prone Members” ProPublica

7. Those who attend AA are a biased sample of motivated people who would do well anyway, with or without AA. Scientific American

8. “The Irrationality of AA”

10. 1.Magnitude of the effect: There are more smokers among patients with carcinoma of the lung 2.Dose Effect: The more you smoke, the higher the risk 3.Consistency: same findings in different studies and in different countries 4.Temporality: Smoking precedes lung cancer 5.Plausibility: Carcinogens in tobacco smoke 6.Specificity: Removal of all confounding factors that could explain the finding by correlation and not causation. Sir Austin Bradford Hill: Smoking and Carcinoma of the Lung (1950)

11. “If we had any thought or knowledge that in any way we were selling a product harmful to consumers, we would stop business tomorrow” George Weissman, VP, 1954

12. Cochrane Review,2011: Intercessory Prayer “Overall, there was no significant difference in recovery from illness or death between those prayed for and those not prayed for” Bradford Hill criteria: 1. Magnitude of the effect - None 2. Dose response effect - None 3. Consistency - None 4. Temporality - None 5. Plausibility - None 6. Specificity - Non e

13. What to do?

14. 1. Magnitude of the effect: Abstinence is 2x higher among AA members 2. Dose response effect: Frequency of attendance correlates with abstinence 3. Consistency: Same results in different samples around the world 4. Temporality: Prior attendance predicts future abstinence 5. Plausibility: This talk will address plausibility 6. Specificity: A problem! May never be fully addressed AA: Bradford Hill criteria (Dr. Lee Ann Kaskutas)

15. There must be coherence with existing knowledge. “AA works because….” Plausibility

17. Why would it work?

18. The Brain Disease Model of Addiction

28. Addiction causes Hypofrontality

31. Helpful traits Poor insight Manipulative Selfish Dishonest Inconsiderate Entitled Unhelpful traits Good insight Generous Honest Considerate Non-demanding What behaviors help the RS achieve its goal?

33. Non-addict (FL) Observes data, then draws a conclusion “Drugs cause problems. I should stop drugs and avoid the problems” Uses logic to draw a conclusion Addict (RS) Starts with a conclusion (“drugs are not a problem”), then manipulates data “How can I use and avoid the problems?” Uses Rationalization to justify initial assumption and makes it look like a logical conclusion The Precontemplative Stage: A different use of logic and reason

34. Talking to a precontemplative brain

35. For the reward system: ABSTINENCE. We know of no other reliable way to reset the pleasure threshold. For the frontal lobes: stop practicing behaviors that fuel addiction. Practice behaviors that promote abstinence. Treatment

36. 1.The disease presents with impaired insight. The addict’s frontal lobes cannot fix themselves. The addict needs a trusted SURROGATE DECISION-MAKER. Internal motivators are almost never enough. 2.The disease presents with undesirable behaviors. The addict should diligently practice the opposite ones: BEHAVIORAL COMPENSATION. Treatment

38. Steps 1-3: A Surrogate Decision-Maker

39. God as we understood him: A Group of Drunks Steps 1-3 Realize that the rational mind has been hijacked by the reward system of the brain to advocate on behalf of alcohol and drugs. Can’t solve the problem alone: alcoholics are making decisions with the affected organ. Steps 1-3 encourage the use of a surrogate decision-maker, since the addict’s own one (the frontal cortex) is affected by the disease. How about God, a Higher Power and Steps 1-3?

40. Behavioral Compensation: Steps 4-12

41. Behavioral Compensation

42. Being insightful, selfless, honest, considerate, altruistic and forgiving. Steps 4 to 12 What traits help the frontal lobe regain control over the RS?

43. Steps 4-12 offer an honest, selfless, altruistic, humble and considerate way of living Addiction is fueled by dishonesty, selfishness, egoism, arrogance and inconsiderate behaviors….all driven by the reward system in its evolutionary quest to “repeat what feels good”. Working the steps

44. How about Step 11? It’s also a frontal lobe exercise

45. -Addiction hijacks the reward system -Addiction affects the frontal lobes -The 12 steps encourages a Surrogate Decision- Making (Steps 1-3) and Behavioral Compensation (Steps 4-12) Is AA Plausible?

46. 1. Magnitude of the effect Abstinence is 2x higher among AA members 2. Dose response effect Frequency of attendance correlates with abstinence 3. Consistency Same results in different samples around the world 4. Temporality Prior attendance predicts future abstinence 5. Plausibility Surrogate Decision-Making, Behavioral Compensation and Behavioral models of change (acceptance, role models, empathy) 6. Specificity A problem! Causation or correlation? AA and Specificity

47. Requires experimental manipulation: randomization, blindness, control groups No realistic opportunity to do this type of research in AA: – Requires a sincere desire to change – AA attracts, does not recruit, its members – Great variability among groups and sponsors – Self-report is unreliable – AA has no opinion on outside matters. AA has done well without the endorsement of academicians or clinicians. AA has no financial interest in its acceptance and success. Due to anonimity, AA does not track its members or conduct research. AA shall remain for ever nonprofessional. AA’s major weakness. It may never be solved. However, AA is widely endorsed: NIH/NIDA, UK NHS, WHO, etc. Yes, it lacks specificity, but AA is free and widely available. 6. Specificity

49. A controversial topic in the recovery community AA is not against MAT How might the controversy be resolved in the future? The case of Raphael Osheroff AA and Medication-Assisted Treatment

50. “Because of the difficulties that many alcoholics have with drugs, some members have taken the position that no one in AA should take medication. While this position has undoubtedly prevented relapse for some, it has meant disaster for others. It becomes clear that just as it is wrong to enable or support any alcoholic to become re-addicted to any drug, it’s equally wrong to deprive any alcoholic of medication that can alleviate or control other disabling physical and/or emotional problems.” AA and Psychiatric Medications September 7, 2010

51. 1970s: Psychiatry was divided on using medications to treat mental illness Dr Osheroff spent 7 months at Chestnut Lodge, where team felt medications will interfere with recovery Lost his practice, his medical license and custody of his 2 sons Raphael Osheroff, MD

52. His parents took him to another hospital. Lithium helped within 3 days, discharged in 3 weeks Osheroff v. Chestnut Lodge: a battle of the experts Arbitration sided for Osheroff: $250,000. He later settled out of court Chestnut Lodge went broke and closed in 2001. Osheroff died in 2012 It’s not opinions, but what the data shows, that constitutes the standard of care Raphael Osheroff, MD

55. Optogenetics: the 2010 “Method of the Year”

56. Using light to turn on/off specific cells in a live animal

57. On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy (Nature, 2013)

58. Reversing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking (Nature 2013) (Optogenetic manipulation of the frontal lobe)

59. Alcohol-addicted rats treated with optogenetics stop drinking (2014)