Presentation on theme: "Implications for Policy The Science of Addiction: Implications for Policy Wilson M. Compton, MD, MPE Director, Division of Epidemiology, Services, and."— Presentation transcript:
Implications for Policy The Science of Addiction: Implications for Policy Wilson M. Compton, MD, MPE Director, Division of Epidemiology, Services, and Prevention Research National Institute on Drug Abuse USA
Addiction DRUG/ALCOHOL Brain Mechanisms Biology Genes/Development Biology Genes/Development Environment Addictions are common, developmental brain diseases expressed as compulsive behavior through continued use of a drug despite negative consequences: Onset depends on many intrinsic and extrinsic factors.
Addictions are brain diseases Human development is key Treatment can be based on neuroscience advances Policies need to account for the nature of addictive disorders
Addictions are brain diseasesAddictions are brain diseases Human development is key Treatment can be based on neuroscience advances Policies need to account for the nature of addictive disorders
Healthy Heart Diseased Heart Decreased Heart Metabolism in Heart Disease ADDICTION IS A DISEASE OF THE BRAIN as other diseases it affects the tissue function Control Cocaine Abuser Decreased Brain Metabolism in Drug Abuse Sources: From the laboratories of Drs. N. Volkow and H. Schelbert High Low
Addictions are brain diseases Human development is keyHuman development is key Treatment can be based on neuroscience advances Policies need to account for the nature of addictive disorders
Addiction Is Developmental Age of Onset of Drug Abuse and Dependence Source: Compton, et al. Archives of General Psychiatry 2007. NESARC Study.
8 Individually Housed Morgan, D. et al. Nature Neuroscience, 2002. * * S.003.01.03.1 0 10 20 30 40 50 Reinforcers (per session) Cocaine (mg/kg/injection) Dominant Subordinate Becomes Subordinate Stress remains Group Housed Becomes Dominant No longer stressed Social Setting Can Change Neurobiology Effects of a Social Stressor on Brain Dopamine D2 Receptors and Propensity to Administer Drugs
0 2 4 6 8 10 012345 Odds ratio ACE Score Ever Addicted Adverse Childhood Experiences (ACE) and Illicit Drug Use (n = 8603) SR Dube, et al. PEDIATRICS 111: 564-572, 2003 1.0
Children with deprivation (n=17) vs controls (n=15) had decreased connectivity in uncinate fasciculus (connects amygdala with frontal cortex), proportional to time in orphanage. This could facilitate heightened emotional reactivity and impaired cognitive control. Social Neglect During Early Childhood Decreases Brain Connectivity Govindan et al., Cereb Cortex 2009 r = -0.604, p=.01
Children with low self-control had poorer health, more wealth problems, more single-parent child rearing, and more criminal convictions and drug use than those with high self-control A gradient of childhood self-control predicts health, wealth, and public safety (Dunedin Study; 1000+ children) HealthWealthCriminal behavior Moffitt et al., PNAS 2011 Since self-control can be improved by interventions early childhood intervention that enhances self-control is likely to bring a greater return on investment than harm reduction programs targeting adolescents alone.
Nurse Home Visiting during pregnancy and the first two years of life has an impact on substance use, mental health and academic achievement at 12 years of age Arch Pediatr Adoles Med, 164(5) 412-418, 2010 Percent of Children Who Used Tobacco, Alcohol, or Marijuana (Last 30 Days) Child Age 12 Percent of Children with Internalizing Problems (Borderline or Clinical) Child Age 12 Scores - Reading & Math – Age 12 (Born to Low-Resource Mothers) PIAT Scores - Reading & Math – Age 12 (Born to Low-Resource Mothers) Percent of Mothers with Role Impairment due to Alcohol or Drug Use – Child Age 12
Addictions are brain diseases Human development is key Treatment can be based on neuroscience advancesTreatment can be based on neuroscience advances Policies need to account for the nature of addictive disorders
AddictionAddiction Reward & well- being MotivationMotivation MovementMovement Dopamine
But Dopamine is only Part of the Story Other neurotransmitter systems are also implicated –Serotonin –Regulates mood, sleep, etc. –Glutamate –Regulates learning and memory, etc. –And Others These and other brain neurochemicals and electrical signals are responsible for your ability to think, move, feel, and behave.
OFC SCC MOTIVATION/ DRIVE MOTIVATION/ DRIVE Hipp Amyg MEMORY/ LEARNING MEMORY/ LEARNING Circuits Involved In Drug Abuse and Addiction Circuits Involved In Drug Abuse and Addiction NAcc VP REWARD PFC ACG EXECUTIVE FUNCTION/ INHIBITORY CONTROL EXECUTIVE FUNCTION/ INHIBITORY CONTROL
NAcc VP REWARD 1. Reward Circuit Drugs of Abuse Engage Systems in the Motivation Pathways of the Brain
Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997. Natural Rewards Elevate Dopamine Levels 0 50 100 150 200 060120180 Time (min) % of Basal DA Output NAc shell Empty Food Sex Box Feeding 100 150 200 DA Concentration (% Baseline) Sample Number 12345678 Female Present
All Drugs Abused by Humans Raise Brain Dopamine Levels in the Nucleus Accumbens Nestler, Nature Neurosci, 2005 ` ` Time After Methamphetamine Dopamine (nM) METHAMPHETAMINE 2000 1500 1000 500 0 2000 1500 1000 500 0 5 5 1 1 2.5 Dose (mg/kg IV) 0 20 40 60 80min 0 100 150 200 250 0 123 hr Time After Nicotine % of Basal Release NICOTINE Di Chiara et al.
TYROSINE DA DOPA DA DA DA DA TYROSINE DA DOPA DA DA DA DA DA DA DA DA DA DA methylphenida te R R R R R R -10010203040 -2 0 2 4 6 8 10 Self-Reports (0-10) Change in Dopamine Bmax/kd (Placebo - MP) “High” Increases in Dopamine are Associated with Perceived “High” raclopride DA Volkow et al., JPET 291(1):409-415, 1999. NAcc VP REWARD
Cocaine Film Cocaine Craving: Population (Cocaine Users, Controls) x Film (cocaine ) Garavan et al A.J. Psych 2000 IFG Ant Cing Cingulate Signal Intensity (AU) Controls Cocaine Users
Cocaine Craving: Population (Cocaine Users, Controls) x Film (cocaine, erotic) Garavan et al A.J. Psych 2000 IFG Ant Cing Cingulate Signal Intensity (AU) Controls Cocaine Users
Dopamine Release Increases when Viewing Cocaine Cues: [ 11 C]Raclopride Binding In Cocaine Abusers (n=18) Viewing a Neutral and a Cocaine-Cue Video Viewing a video of cocaine scenes decreased specific binding of [11C]raclopride presumably from DA increases Neutral video Volkow et al J Neuroscience 2006
3.Motivation & Executive Control Circuits ACG OFC SCC INHIBITORY CONTROL INHIBITORY CONTROL EXECUTIVE FUNCTION EXECUTIVE FUNCTION PFC MOTIVATION/ DRIVE MOTIVATION/ DRIVE Dopamine is also associated with motivation and executive function via regulation of frontal activity.
Controls Methamphetami ne Abusers OFC umol/100gr/min 4 0 Controls Alcoholics control addicted Brain glucose metabolism Control Cocaine Abuser DA D2 receptors Relationship Between Brain Glucose Metabolism and Striatal D2 Receptors Volkow et al., PNAS 2011 108(37): 15037-42
ACG OFC SCC Hipp NAcc VP Amyg REWARD INHIBITORY CONTROL INHIBITORY CONTROL MEMORY/ LEARNING MEMORY/ LEARNING EXECUTIVE FUNCTION EXECUTIVE FUNCTION PFC Becomes severely disrupted in ADDICTION MOTIVATION/ DRIVE MOTIVATION/ DRIVE The fine balance in connections that normally exists between brain areas active in reward, motivation, learning and memory, and inhibitory control
Drive OFC Drive OFC Saliency NAc Saliency NAc Memory Amygdala Memory Amygdala Control CG Control CG Non-Addicted Brain Non-Addicted Brain Addicted Brain Addicted Brain STOP GO Drive Memory Saliency Control Drive Memory Saliency Stress Reactivity Stress Reactivity
Effective Strategies Attend to Multiple Aspects of Addiction: Behavior Biology Social Context
A Double Blind, Placebo Controlled Trial Of NEPICASTAT (Dβh Inhibitor) In Cocaine Dependence[Biotie/NIDA] Nepicastat attenuates cue-induced reinstatement of cocaine seeking Schroeder et al., Neuropsychopharmacology. 2013 Devoto et al., Addict Biol. 2013 Nepicastat increases DA in PFC (but not in Nac) Improving Prefrontal Function
NIDA Criminal Justice Drug Abuse Treatment Studies (CJ-DATS) National Drug Abuse Treatment Clinical Trials Network (CTN) National Drug Abuse Treatment Clinical Trials Network (CTN) Research Centers CTN Sites
Addictions are brain diseases Human development is key Treatment can be based on neuroscience advances Policies need to account for the nature of addictive disordersPolicies need to account for the nature of addictive disorders
Left, dMPFC activation associated with argument strength (AS) by “message sensation value” MSV interaction predicted cotinine levels one month after add presentation. Wang A et al. J. Neurosci. 2013;33:7420-7427 Brain and Behavioral Impact of Televised Anti-Tobacco Public Service Announcements: Predictive Value
Addressing Drugs and Crime Public Health Approach - disease - disease - treatment - treatment Public Safety Approach - illegal behavior - illegal behavior - punish - punish High Attrition High Recidivism High Recidivism
Successful Reentry Programs Use an Integrated Public Health-Public Safety Strategy Blends functions of criminal justice and treatment systems to optimize outcomes Community- based treatment Opportunity to avoid incarceration or criminal record Close supervision Consequences for noncompliance are certain and immediate
Summary: Drug Addiction is a Brain Disease Involving Reward, Memory and Control Circuits Addiction comes about by laying down and strengthening new memory connections in various circuits in the brain. Long-lasting brain changes are responsible for the distortions of thought and emotionthat characterize addicts, including the compulsion to use drugs that is the essence of addiction. Policies to prevent and treat addiction can benefit from an understanding of the science of addiction. Policies to prevent and treat addiction can benefit from an understanding of the science of addiction.