Leading Causes of Death
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1 Slide 1 Is Addiction Really a Disease? Kevin T. McCauley, M.D. The Institute for Addiction Study Park City, Utah AddictionDoctor.com Slide 2 Leading Causes of Death 1. Heart Disease 2. Cancer 3. Stroke/High Blood Pressure 4. Chronic Lung Disease 5. Accidents 11. Suicide 12. Liver Disease/Cirrhosis 14. Homicide Slide 3 Choice Free Will exists Responsibility Can stop Punishment and Coercion DO work BEHAVIORS vs. Disease No Free Will No Responsibility Can t stop Punishment and Coercion DON T work SYMPTOMS 1
2 Slide 4 Slide 5 Is Addiction Really a Disease? so this is a question about CAUSALITY Slide 6 The Disease Model (a CAUSAL model) 2
3 Slide 7 Slide 8 If ever we could fit addiction into this model, then it would win admission into The Disease Club... Slide 9 And now, we finally can 3
4 Slide 10 Addiction is a disorder of 1. GENES (vulnerability) 2. PLEASURE (reward system) 3. MEMORY (learning) 4. STRESS (anti-reward system) 5. CHOICE (motivation) Slide 11 Five Theories of Addiction 1. Genetic Vulnerability (Schuckit et al) 2. Incentive-sensitization of Reward (Robinson & Berridge) 3. Pathology of Learning & Memory (Hyman, Everitt & Robbins) 4. Stress and Allostasis (Koob & LeMoal) 5. Pathology of Motivation and Choice (Kalivas & Volkow) Slide 12 Addiction is a disorder of 1. GENES (vulnerability) 4
5 Slide 13 Genetic Vulnerability Genetic difference determine low responders vs. high responders to the effects of alcohol There are genetic differences in how people respond to methylphenidate injections (some like, some don t care) implying different vulnerabilities For addicts, drugs really do feel different than they do to non-addicts Does cocaine feel better to an pre-addict than to a normal person? Slide 14 Addiction is a BRAIN disease The brain s a HARD organ - very complex and difficult to study There are no good tests for brain diseases (yet) So people with brain diseases start out at a disadvantage The symptoms of brain diseases are more likely to be labeled as badness Slide 15 The Brain Localizes Functions Learned this from brain injury patients Vast majority die Some live These folks are very helpful to neurological research Can correlate the damage visible on CT scan with the patient s impairment 5
6 Slide 16 Mapping the Brain Correlating symptoms of impairment with observed lesions on neuroimaging studies Slide 17 The Frontal Cortex Confers emotional meaning (semantic content) onto objects in the world Seat of the Self and Personality Love, Morality, Decency, Responsibility, Spirituality Conscious choice Slide 18 The Frontal Cortex: Defective in addiction? Where drugs work? Addict personality? Sociopathy? Self-centeredness? Character defects? Immorality? Weak will? Poor socialization? Bad parenting? 6
7 Slide 19 But drugs don t work in the Frontal Cortex... Drugs work in the Midbrain Slide 20 The Midbrain is the SURVIVAL brain Not conscious Acts immediately, no future planning or assessment of longterm consequences A life-or-death processing station for arriving sensory information Slide 21 The Midbrain (aka Limbic Brain) is your SURVIVAL brain. It handles: EAT! KILL! SEX! 7
8 Slide 22 Olds experiments: where do drugs work? (where are they reinforcing/pleasurable?) Slide 23 Olds experiments: no drug self-administration anywhere in the cortex Slide 24 Mice preferentially self-administer drugs of abuse like cocaine ONLY to the Reward Centers of the Midbrain To the exclusion of all other survival behaviors To the point of death 8
9 Slide 25 Mice get addicted to drugs, but Mice don t weigh moral consequences Mice don t consult their Mouse God Mice aren t sociopaths Mice don t have bad parents There are no Mouse Gangs Slide 26 In addiction, the drug hijacks the survival hierarchy and is so close to actual survival that it is indistinguishable from actual survival New #1: DRUG! 2. EAT! 3. KILL! 4. SEX! Slide 27 Brain Perceptual Systems (all of them): 1. Vision 2. Hearing 3. Touch 4. Smell 5. Taste 6. Linear Acceleration (balance) 7. Angular Acceleration (balance) 8. Gravity (Proprioception, aka position sense) 9. Blood po2 and pco2 levels 10. Pleasure (addiction is a broken pleasure sense ) 9
10 Slide 28 Addiction is a disorder of 1. GENES (vulnerability) 2. PLEASURE (reward system) Slide 29 Addiction Neurochemical #1: Dopamine All drugs of abuse and potential compulsive behaviors release Dopamine Dopamine is first chemical of a pleasurable experience - at the heart of all reinforcing experiences DA is the neurochemical of salience (it signals survival importance) DA signals reward prediction error Tells the brain this is better than expected Slide 30 Addiction is a disorder of 1. GENES (vulnerability) 2. PLEASURE (reward system) 3. MEMORY (meaning) 10
11 Slide 31 Addiction Neurochemical #2: Glutamate The most abundant neurochemical in the brain Critical in memory formation & consolidation All drugs of abuse and many potentially addicting behaviors effect Glutamate which results in long-lasting neuroplastic changes in the brain & preservation of drug memories Glutamate is the currency of motivation Slide 32 DOPAMINE (DA) GLUTAMATE (Glu) All drugs of abuse and potential compulsive behaviors INCREASE DA Reward salience this is important! I really need this! Rostral projections: PFC < NA < VTA All drugs of abuse and potential compulsive behaviors EFFECT Glu Drug memories Drug seeking OK, I ll remember Fine, go and get some Caudal projections: PFC > NA Slide 33 Dopamine-Releasing Chemicals Alcohol & Sedative/Hypnotics Opiates/Opioids Cocaine Amphetamines Entactogens (MDMA) Entheogens/Hallucinogens Dissociants (PCP, Ketamine) Cannabinoids Inhalants Nicotine Caffeine Anabolic-Androgenic Steroids 11
12 Slide 34 Drugs cause Dopamine Surges in the midbrain reward system Slide 35 Dopamine-Releasing Behaviors Food (Bulimia & Binge Eating) Sex Relationships Other People ( Codependency, Control) Gambling Cults Performance ( Work-aholism ) Collection/Accumulation ( Shop-aholism ) Rage/Violence Media/Entertainment Slide 36 The Full Spectrum of Addiction Alcohol & Sedative/Hypnotics Opiates/Opioids Cocaine Amphetamines Entactogens (MDMA) Entheogens/Hallucinogens Dissociants (PCP, Ketamine) Cannabinoids Inhalants Nicotine Caffeine Anabolic-Androgenic Food (Bulimia & Binge Eating) Sex Relationships Other People ( Codependency, Control) Gambling Cults Performance ( Work-aholism ) Collection/Accumulation ( Shop-aholism ) Rage/Violence Media/Entertainment 12
13 Slide 37 In addicted mice, the drug goes to the top of the list, hijacking the normal survival hierarchy New #1: DRUG! 2. EAT! 3. KILL! 4. SEX! Slide 38 In addiction, the drug is equated with survival at the level of the unconscious (i.e. the drug IS survival) Slide 39 In addiction: a line is crossed > NON-ADDICT (never used drugs) (experimented in past) (uses drugs) (abuses drugs) DRUG = DRUG ADDICT DRUG = SURVIVAL 13
14 Slide 40 Addiction is a disorder of 1. GENES (vulnerability) 2. PLEASURE (reward system) 3. MEMORY (meaning) 4. STRESS (anti-reward system) Slide 41 Relapse Three things that are known to evoke relapse in humans: 1. Exposure to drug cues 2. Stress 3. Brief exposure to drug itself (commonality: DA release?) (an example of a dangerous relapse-triggering behavior: talking about drugs (cues) with other newly-sober addicts in treatment (stressed) while smoking (DA release) Slide 42 STRESS : a major player in addiction & relapse 14
15 Slide 43 We all face stress, yes... But we don t all: Face the same severity of stress Face the same pattern of stress Have the functioning coping mechanisms Come to the table with the same brain Slide 44 CHRONIC, SEVERE STRESS = CRF and CRF = DAD2 receptors and DAD2 receptors = Anhedonia Anhedonia: Pleasure deafness (the patient is no longer able to derive normal pleasure from those things that have been pleasurable in the past) Slide 45 Drugs cause Dopamine Surges in the midbrain reward system 15
16 Slide 46 The Dopamine surge causes the drug to be tagged as the new, #1 coping mechanism for all incoming stressors Slide 47 Addiction is a disorder of 1. GENES (vulnerability) 2. PLEASURE (reward system) 3. MEMORY (meaning) 4. STRESS (anti-reward system) 5. CHOICE (motivation) Slide 48 Now that the midbrain has found what secures survival how does it motivate the individual to repeat that behavior? 16
17 Slide 49 Stress = Craving Slide 50 Why the Choice Argument fails It fails to take into account CRAVING The Choice Argument measures addiction only by the addict s external behavior It ignores the inner suffering of the patient You don t actually have to have drug use for the defective physiology of addiction to be active The addict cannot choose to not crave Slide 51 Orbitofrontal Cortex Senior executive of the emotional brain An association cortex: integrates sensory information Affective value of reinforcers Expectation of drug reward Decision-making, sensory integration, affect regulation Activated during intoxication and craving De-activated during withdrawal 17
18 Slide 52 ventro-medial Prefrontal Cortex Research on patients with vmpfc lesions Myopia for the future, cognitive impulsiveness - prefer immediate but disadvantagous rewards over delayed rewards advantageous in the long run - guided primarily by immediate prospects and insensitive to pos or neg future consequences - also: preferred low immed punishment over higher immediate punishment c greater advantage over time - deny or are unaware of the problem vmpfc pts similar to Substance Abusing patients Slide 53 FRONTAL HYPOFUNCTIONALITY: during craving states the cortex actually shuts off Slide 54 It s not that the addict doesn t have values... It s that in the midst of the survival panic of craving the addict cannot draw upon those values to guide their behavior... The midbrain now reigns... And conscious thought becomes constricted (i.e. free will fails) 18
19 Slide 55 How do we restore the Frontal Cortex? Slide 56 misperception of the hedonic aspects of the drug And attribution of survival salience to the drug on the level of the unconscious Addiction Part One: Slide 57 Addiction Part Two: The drug takes on personal meaning The addict develops an emotional relationship with the drug The addict derives their sense of self and exerts agency through the drug 19
20 Slide 58 The Two Tasks of Addiction Treatment: 1. To give the addict workable, credible tools to proactively manage stress and decrease craving 2. For each individual addict, find the thing which is more emotionally meaningful than the drug - and displace the drug with it Slide 59 The Division of Labor: Slide 60 With the installation of coping mechanisms (A.A.), the Cortex comes back on-line and Free Will returns 20
21 Slide 61 Then... Slide 62 Definition of Addiction: Addiction is a dysregulation of the midbrain dopamine (pleasure) system due to unmanaged stress resulting in symptoms of decreased functioning, specifically: 1. Loss of control 2. Craving 3. Persistent drug use despite negative consequences Slide 63 Addiction fits the Disease Model! 21
22 Slide 64 Something very important happened when we were finally able to call addiction a disease... Slide 65 If Addiction is a Disease, then Addicts are patients! Addicts have the same rights as all patients All the ethical principles that apply to other patients now also apply to addicts Addiction has parity Slide 66 Addiction IS a Disease! Everything treatment centers SAY is Addiction is a Disease But everything they DO shows that they don t really believe that themselves 22
23 Slide 67 So the punishment IS the problem... (treatment fails because it s punitive) Slide 68 What if we took punishment out of the treatment? (Is there a group of addicts we don t punish?) Slide 69 PILOTS! 23
24 Slide 70 Things we do for pilots: 1. Medical Detoxification 2. Inpatient or Residential Treatment 3. Aftercare: Immediately after treatment for Three to Five Years 4. A.A. Attendance 5. Regular testing ( monitoring ) 6. Return to duty 7. Personal physician Slide 71 Treatment Outcome Variance in Pilots Treated for Alcoholism: The United States Navy enjoys a 95-97% return to flying status rate in its pilots treated for alcoholism. - Joseph A. Pursch, M.D. Since the inception of its impaired pilot program in conjunction with the FAA and ALPA EAPs, UAL has an 87% return to flight status rate in pilots treated for alcohol problems. - Stanley Mohler, M.D. Slide 72 Questions? References available on request Please contact: Kevin McCauley The Institute for Addiction Study kevintmccauley@hotmail.com Please also see: ( 2008, Kevin T McCauley, not for resale, all rights reserved) 24
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