Neuroscience of Drug Dependence: Influence on Crime and Punishment

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1 Neuroscience of Drug Dependence: Influence on Crime and Punishment Thomas Kosten MD JH Waggoner Chair & Professor of Psychiatry, Pharmacology & Neuroscience Associate Dean for Clinical Research Baylor College of Medicine Past President American Academy of Addiction Psychiatry

2 Disclosure Thomas Kosten, MD Speakers Bureau: Cephalon, Forrest, Reckitt- Benkizer Consultant: Novartis, Bristol Myers Squibb, Celtic, Alkermes, Synosia, Catalyst, Lannacher, Gerson Lerman Consultants Stock ownership: Pfizer, Johnson & Johnson.

3 Neuroscience of Drug Dependence Cocaine, Alcohol and Brain damage In Tom s Tragic Life of Crime

4 Tom s Drug Abuse History Started alcohol use at age 8 years Started using drugs before adolescence Drugs completely disrupted his school, family, social and athletic life from age 12 Within 5 years (age 17) he showed major deterioration in behavior and cognition First medical detoxification at age 18

5 Tom s Alcohol Dependence Start age 8, weekly intoxication by age 14, daily intoxication by age 16, severe withdrawal symptoms by age detoxifications over 10 years (age 18-28) Extended inpatient care needed by age 21 Significant liver and brain damage (blackouts) Delerium tremens possibly at age 20 and definitely by age 28 (15% of these patients die)

6 Tom s Cocaine Dependence Start at age 14, weekly binges of 2-3 hours Age 16 daily smoked cocaine alternating with binges lasting 3 days (not sleep or eat) Severe withdrawal including hallucinations, panic and paranoia, treat himself with antipsychotic medications to reduce withdrawal Heavy cocaine use documented on urine toxicologies and his hospital stays.

7 Tom s Other Drug Abuse Opiates (heroin, percodan) since age 16 Heroin use daily (15 bags/day) by age 22 Required multiple opiate detoxifications Cannabis since age 12, with daily use by age 14 (6 joints/day) Benzodiazepines since age 14, binges by 16 Nicotine since age 12, supplied by mother

8 Tom s Hospitalizations Records for at least 6 hospitalizations and extended care (months) residential treatments Consistent reports of extensive drug and alcohol use, and need for detoxification Cocaine use consistently reported as $ per day from 1994 to 1998 treatment episodes Only periods of non-use appear to be in prison

9 How alcohol and cocaine damage your brain

10 Reduced brain blood flow due to cocaine

11 Cocaine Reduces Brain Blood Flow When using cocaine, the brain s blood flow is reduced by 30% After repeatedly using cocaine for months or years, the brain develops holes (like many small stokes) from lack of blood flow Patients with these holes in their brains have marked trouble thinking, concentrating and making decisions

12 Cocaine reducing brain blood flow (yellow good blood flow, blue poor blood flow)

13 Brain blood flow continues to show holes in brain for months after becoming cocaine abstinent Volkow et al., BMJ 1988 Holman et al., J Nuc Med 1991, 93 Weber et al., J Nuc Med 1993 Strickland et al., J NP & CNS 1993 Kosten et al., DAD 1998

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15 Reduced brain blood flow impairs cocaine abusers ability to concentrate, think and decide their actions rationally

16 Less brain blood flow leads to more problems in concentration Woods 1991 Cocaine abusers were tested after they had not used cocaine in a month Cocaine abusers were seriously impaired on 10% to 50% of 20 tests measuring thinking and concentration Less brain blood flow was directly related to greater impairment on these tests of concentration, thinking, and deciding about everyday events and problems

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18 Cocaine abusers, even after being abstinent for several weeks, can not properly pay attention to important visual cues in other people such as indications of sadness and perhaps of terror

19 Visual activation in brains of healthy normals (RED/yellow = activation) Z= -3mm Z= 0mm Z= 3mm T-score

20 Reduced visual activation in brains of cocaine abusers (RED/yellow = activation) Z= 9mm Z= 12mm Z= 15mm T-score

21 What does reduced brain activation mean? Cocaine abusers can not understand complex events that they are seeing Cocaine abusers can not decide quickly what to do when they see something unexpected happen right in front of them Cocaine abusers persist in doing the same thing, even when what they see should change what they are doing

22 Healthy normal people show substantial brain activation when watching a video of sad people. Cocaine abusers do not perceive emotions in other people such as sadness and perhaps terror.

23 Brain activity during Sad Video 1 1. Healthy normals vs 2. Cocaine addicts 2 Yellow/red good blood flow, Blue poor blood flow

24 Cocaine abusers pay attention to reminders of cocaine use, but ignore emotions in other people such as sadness and perhaps terror.

25 Brain activity in cocaine abusers while watching cocaine using vs sad people Cocaine vs. Sad

26 Cocaine disrupts visual understanding of normal events Brain activation to visual events reduced by recent cocaine use Brain activation in cocaine abusers is reduced in visual areas used to understand, judge, and decide about things the cocaine abuser is seeing This lack of brain processing makes cocaine abusers persist in doing the same thing, even when what they see should change what they are doing

27 Is it hopeless for cocaine abusers? NO! IT IS NOT HOPELESS, even stoke victims can recover movement and speech Cocaine abusers brains can be repaired by as little as several months of sustained abstinence from cocaine and other drugs Concentration, thinking and ability to make rational decisions may take several years to recover, but in these young adults recover

28 Alcohol and Brain Damage

29 Cocaine and Alcohol together are more toxic to the Brain than either alone A cocaine-like chemical is formed by the action of alcohol on cocaine. This chemical stays in the brain three times longer than cocaine and is more damaging than cocaine to brain cells.

30 Cocaine and Alcohol disrupt brain pathways involved in normal pleasure

31 Cocaine induces prolonged deficiencies in the brain s communication between brain cells Communication between brain cells is essential for normal sensations, actions, thought and judgment

32 Damage to brain communication after chronic cocaine abuse Dopamine is a chemical in the brain that is allows communication between neurons Dopamine communication between neurons is markedly damaged by cocaine and alcohol Loss of dopamine leads to Parkinson s disease (e.g. Mohammad Ali s inability to move) Dopamine loss also leads to depression and inability to experience pleasure in ordinary life

33 How Cocaine Alters the Brain: Dopamine Damage & Parkinsonism Receptor Sensitivity Sites of Drug Action at the Synapse Normal Dopamine Receptors Dopamine Reuptake Dopamine Overactivity Dopamine Reuptake Dopamine Receptor Receptor

34 Cocaine Abuse REDUCES Dopamine Brain Cells normal subject cocaine abuser (1 month post) cocaine abuser (4 months post)

35 Parkinsonian (PD) Brain Abnormalities in Cocaine Abusers %ID/cc Control Amphetamine Cocaine PD

36 Dopamine Reduction In Drug Addiction leads to needing Drugs to Feel Rewarded DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA DA Reward Circuits Reward Circuits Non Drug Abuser Addicted Subject

37 Conclusions from Studies of Cocaine and Alcohol Effects Brain blood flow reduced by drugs Brain cell communication impaired by drugs Leads to inability to judge and reason normally Acute craving for drugs dominates behavior Paranoia and perseveration during withdrawal Recovery of reasoning and judgment occurs over several months of abstinence

38 Tom s Crime #1 During a 2 day binge of drinking & smoking cocaine and marijuana with his aunt Sue, Tom became Paranoid that she was going to turn him into police for drug use so he planned to kill her in her sleep He was staying at her house and went into her bedroom and stabbed her over 50 times Her two young children were in bed with her and he also killed them

39 Tom s Crime #2 Tom repeatedly stated that he had no intent to kill the children and did not know they were there in bed He also killed the sleeping dog in the bed He remembers a loud noise like stepping on a cat s tail which he later said was probably a child scream

40 Tom s Crime #3 After the stabbing he stole her purse, ran out and dropped the bloody knife in the yard He got in his Aunt s car and drove to where he bought heroin & cocaine usually and was dragged by cocaine dealer car, as he tried to get more cocaine from this dealer Shot up a large dose of cocaine and heroin He showed up 3 hours later in the Emergency Room with a heroin overdose

41 Tom s Specific Mental State at time of killings #1 Paranoia induced by cocaine (plan to kill Aunt Sue) Perseveration induced by cocaine (stabbing frenzy of overkill) Killing children & dog disorganized him Child scream is misperceived as sounding like stepping on a cat s tail and its significance does not stop his actions

42 Tom s mental state at time of killings #2 Short cocaine high, then quest for more cocaine his focus on craving and money for cocaine, not on rational behavior to avoid being caught for the killings Dropping knife in yard is simply illogical behavior and disorganization Alcohol increased impulsiveness and perseveration with inability to stop actions, even when it was irrational to continue them (killing children, over 50 lethal stabs)

43 Behavior after killing Focused on getting more drugs Driven to get drugs, even when it causes direct and immediate harm to him (being dragged by car, when trying to get cocaine from a dealer after the killing) Drugs to blunt emotional effects and even memory of the killings Resulting overdose from heroin

44 Tom s evaluation 2 years later Normal brain scans on SPECT and MRI This is expected from brain s ability to repair itself after many months of drug abstinence, good nutrition and regular exercise like he had in prison Brain cells can grow back and do (patients recover even from major strokes)

45 Neuropsychological Tests 2 years after last drug use Expected recovery of functioning compared to time of intoxication and withdrawal from the cocaine and alcohol Intoxication effect of opiates and marijuana at time of killing are also transient and gone within a week of stopping these drugs

46 The descent to Hell is easy; The gates stand open day and night; But to reclimb the slope, And escape to the upper air, This is labor. Virgil, The Aeneid Book VI, Line 126

47 The Labor of Treatment Treatment agents are available and effective and based on neuroscience of addiction Relapse prevention agents for alcohol Maintenance agents for opiates - buprenorphine Blocking agents for stimulants - vaccine

48 Alcohol Relapse Prevention Naltrexone Depot Naltrexone Disulfiram Acamprosate effective in European but not American trials Investigational Serotonin reuptake inhibitors Buspirone Tricyclic antidepressants Topiramate

49 Buprenorphine for Office-Based Opioid Treatment Office-based maintenance or detox is made possible by Drug Abuse Treatment Act of 2000 (DATA) Stipulated that medication had to be Schedule III. FDA approved October 2002 Other provisions: Physicians had to meet certain criteria, either by prior training & certification or by taking an 8-hour course A physician could not treat more than 30 patients at any one time Changed to 100 patients in 2006 Initial higher percentage of Caucasians, women, & prescription opioid abusers has been changing

50 Cocaine ANTAGONIST: Active Immunization Vaccine, combo of cocaine analog & carrier protein Repeated injections of vaccine (4-5x, over 2-3 mo.) stimulate production of antibodies (IGg) Antibodies selectively bind to cocaine Preventing (slowing down) entry of cocaine into brain Cocaine metabolism not changed

51 Pros: Cocaine Vaccine Guaranteed continuous & extended effect Cons: Takes time & repeated injections for AB to develop & frequent boosters may be necessary Great individual variability in AB levels (sufficient levels only in 70% of patients) Effect is potentially surmountable therefore selection of patients will be important Should be used in highly motivated patients May block lapse from becoming a relapse

52 Model of Stimulant Addiction Treatment A staged treatment & a treatment that combines medication with therapy appropriate for the particular stage of treatment may have the best results Reduction in reinforcing effects Diminishing effects of cues Psycho- Pharmacotherapy Disulfiram d-amph Modafinil VACCINE Baclofen Tiagabine Topiramate ACTIVE USE INITIAL ABSTINENCE SUSTAINED ABSTINENCE Contingency Management Relapse Prevention

53 Thank You Questions?