Presentation on theme: "The Science of Addiction: Implications for Policy Wilson M"— Presentation transcript:
1 The Science of Addiction: Implications for Policy Wilson M The Science of Addiction: Implications for Policy Wilson M. Compton, MD, MPE Director, Division of Epidemiology, Services, andPrevention ResearchNational Institute on Drug AbuseUSA
2 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.BiologyGenes/DevelopmentEnvironmentDRUG/ALCOHOLBrain MechanismsAddiction
3 Addictions are brain diseases Human development is keyTreatment can be based on neuroscience advancesPolicies need to account for the nature of addictive disorders
4 Addictions are brain diseases Human development is keyTreatment can be based on neuroscience advancesPolicies need to account for the nature of addictive disorders
5 ADDICTION IS A DISEASE OF THE BRAIN as other diseases it affects the tissue functionControl Cocaine AbuserDecreased Brain Metabolism in Drug AbuseHighLowDecreased Heart Metabolism in Heart DiseaseHealthy HeartDiseased HeartSources: From the laboratories of Drs. N. Volkow and H. Schelbert
6 Addictions are brain diseases Human development is keyTreatment can be based on neuroscience advancesPolicies need to account for the nature of addictive disorders
7 Addiction Is Developmental Age of Onset of Drug Abuse and Dependence Addiction is also characterized as a developmental disorder characterized by increased risk for substance use disorder for tobacco MJ and alcoholThere are many factor that contribute to the increase in incidence including-Social/ environmental factors- Genetic andNeurobiological factors (Sowell brain volume subtraction method between normal year old adolescents and year old young adults revealed parietal, temporal and occipital lobes showed little maturational change but, importantly, dorsal, medial and lateral regions of the frontal lobes (purple) those regions involved in executive function and inhibitory control were less developed.Adolescents with risk haplotype on Chromosome 15 that start smoking before age 15 go on to become more dependent to tobacco as adults than those with other haplotypesUniversal Prevention intervention research is aimed at developing and testing programs that can reduce drug initiation and use during this vulnerable developmental period.Age of Onset of Drug Abuse and DependenceSource: Compton, et al. Archives of General Psychiatry NESARC Study.
8 Reinforcers (per session) Effects of a Social Stressor on Brain Dopamine D2 Receptors and Propensity to Administer Drugs*S.003.01.03.11020304050Reinforcers (per session)Cocaine (mg/kg/injection)DominantSubordinateIndividuallyHousedBecomes SubordinateStress remainsGroupHousedBecomes DominantNo longer stressedSocial Setting Can Change NeurobiologyMorgan, D. et al. Nature Neuroscience, 2002.
9 Adverse Childhood Experiences (ACE) and Illicit Drug Use (n = 8603) 246810135Odds ratioACE ScoreEver Addicted1.0SR Dube, et al. PEDIATRICS 111: , 20039
10 Social Neglect During Early Childhood Decreases Brain Connectivity r = , p=.01Children 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.Govindan et al., Cereb Cortex 2009
11 A gradient of childhood self-control predicts health, wealth, and public safety (Dunedin Study; children)HealthWealthCriminal behaviorChildren 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-controlMoffitt et al., PNAS 2011Since 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.
12 Nurse Home Visiting during pregnancy and the first two years of life Results from the 2008 National Survey on Drug Use and Health (NSDUH)Substance Abuse and Mental Health Services AdministrationNurse Home Visiting during pregnancy and the first two years of lifehas an impact on substance use, mental health and academic achievement at 12 years of agePercent of Children Who Used Tobacco,Alcohol, or Marijuana (Last 30 Days)Child Age 12Percent of Children with Internalizing Problems(Borderline or Clinical)Child Age 12PIAT Scores - Reading & Math – Age 12 (Born to Low-Resource Mothers)Percent of Mothers with Role Impairmentdue to Alcohol or Drug Use – Child Age 12Arch Pediatr Adoles Med, 164(5) , 2010
13 Addictions are brain diseases Human development is keyTreatment can be based on neuroscience advancesPolicies need to account for the nature of addictive disorders
14 Dopamine Movement Motivation Addiction Reward & well-being It’s About Dopamine (mostly)Dopamine is the brain’s primary “pleasure chemical”Dopamine plays a role in attention, problem solving, and the anticipation of rewardDopamine is implicated in the drug high, as well as in the craving that accompanies withdrawal.Dopamine is a brain chemical involved in many different functions including movement, motivation, reward — and addiction. Nearly all drugs of abuse directly or indirectly increase dopamine in the pleasure and motivation pathways and in so doing, alter the normal communication between neurons.AddictionReward & well-being
15 But Dopamine is only Part of the Story Other neurotransmitter systems are also implicatedSerotoninRegulates mood, sleep, etc.GlutamateRegulates learning and memory, etc.And OthersDopamine is an important brain chemical in drug abuse and addiction, but other brain systems and brain chemicals are also involved. Serotonin and glutamate neurotransmitter systems, for example, are among those affected. These neurotransmitters are important regulators of mood, sleep, learning and memory, and more.These and other brain neurochemicals and electrical signals are responsible for your ability to think, move, feel, and behave.
16 Why Can’t Addicts Just Quit? Key Question:Why Can’t Addicts Just Quit?
17 Drug Abuse and Addiction Circuits Involved InDrug Abuse and AddictionPFCACGEXECUTIVE FUNCTION/INHIBITORYCONTROLOFCSCCMOTIVATION/DRIVEHippAmygMEMORY/LEARNINGNAccVPREWARD
18 Drugs of Abuse Engage Systems in the Motivation Pathways of the Brain NAccVPREWARDReward CircuitDrugs of Abuse EngageSystems in theMotivationPathwaysof the Brain
19 Natural Rewards Elevate DA Concentration (% Baseline) Dopamine LevelsFoodSex200200NAc shell150150Natural rewards stimulate dopamine neurotransmission. Eating something that you enjoy or being stimulated sexually can cause dopamine levels to increase. In these graphs, dopamine is being measured inside the brains of animals. Its increase is shown in response to food or sex cues. This basic mechanism of controlled dopamine release and reuptake has been carefully shaped and calibrated by evolution to reward normal activities critical for our survival.DA Concentration (% Baseline)% of Basal DA Output100100Empty50Box FeedingFemale Present1234567860120180SampleNumberTime (min)Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997.19
20 All Drugs Abused by Humans Raise Brain Dopamine Levels in the Nucleus Accumbens `Time After MethamphetamineDopamine (nM)METHAMPHETAMINE200015001000500512.5Dose (mg/kg IV)min250NICOTINE200% of Basal Release150100123 hrTime After NicotineNestler, Nature Neurosci, 2005Di Chiara et al.
21 Increases in Dopamine are Associated with Perceived “High” NAccVPREWARDTYROSINETYROSINEDOPADOPADADADADADADADA-1010203040-22468Self-Reports(0-10)Change in DopamineBmax/kd (Placebo - MP)“High”DADAracloprideDADADAmethylpnidaDADAracloprideDARRDADADARRRRVolkow et al., JPET 291(1): , 1999.21
22 “People, Places and Things…” HippAmygMEMORY/LEARNING2. Memory circuit“People, Places and Things…”
23 Cocaine Craving:Population (Cocaine Users, Controls) x Film (cocaine )CingulateAnt CingSignal Intensity (AU)Cocaine FilmIFGControls Cocaine UsersGaravan et al A .J. Psych 2000
24 Cocaine Craving:Population (Cocaine Users, Controls) x Film (cocaine, erotic)CingulateAnt CingSignal Intensity (AU)IFGControls Cocaine UsersGaravan et al A .J. Psych 2000
25 Volkow et al J Neuroscience 2006 Dopamine Release Increases when Viewing Cocaine Cues: [11C]Raclopride Binding In Cocaine Abusers (n=18) Viewing a Neutral and a Cocaine-Cue VideoNeutral videoViewing a video of cocaine scenes decreased specific binding of [11C]raclopride presumably from DA increasesVolkow et al J Neuroscience 2006
26 ACGOFCSCCINHIBITORYCONTROLEXECUTIVEFUNCTIONPFCMOTIVATION/DRIVEMotivation & ExecutiveControl CircuitsDopamine is also associated with motivation and executive function via regulation of frontal activity.
27 Relationship Between Brain Glucose Metabolism and Striatal D2 Receptors304050607080902.9126.96.36.199.43.53.6D2 Receptors (BPND)354555651.8188.8.131.52.8ControlCocaine Abusercontrol addictedBrain glucose metabolismControlsMethamphetamineAbusersumol/100gr/minOFC4ControlsAlcoholicsVolkow et al., PNAS (37):DA D2 receptors
28 ADDICTION Becomes severely disrupted in The fine balance in connections that normally existsbetween brain areas active in reward, motivation,learning and memory, and inhibitory controlEXECUTIVEFUNCTIONPFCACGINHIBITORYCONTROLHippOFCREWARDSCCNAccVPMOTIVATION/DRIVEAmygMEMORY/LEARNINGBecomes severely disrupted inADDICTION
30 Effective Strategies Attend to Multiple Aspects of Addiction: BehaviorBiologySocial Context
31 Improving Prefrontal Function A Double Blind, Placebo Controlled Trial Of NEPICASTAT (Dβh Inhibitor) In Cocaine Dependence[Biotie/NIDA]Nepicastat attenuates cue-induced reinstatement of cocaine seekingNepicastat increases DA in PFC (but not in Nac)Schroeder et al., Neuropsychopharmacology. 2013Devoto et al., Addict Biol. 2013
32 Treatment Clinical Trials Network (CTN) National Drug AbuseTreatment Clinical TrialsNetwork (CTN)NIDA Criminal Justice Drug Abuse Treatment Studies (CJ-DATS)The CTN framework consists of thirteen Nodes linked with Community-based Treatment programsThe sites for these networks span the us and provide an extensive net opportunity to test the efficacy of novel treatment for addiction in both a public health and public safety environment50-66% of inmates meeting standard diagnostic criteria for alcohol/drug dependence or abuse, according to the Bureau of Justice Statistics. Mumola CJ and Kerberg JC. Drug use and dependence, state and federal prisoners, Washington, DC: U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics, 2006.The vast majority of criminal offenders who would benefit from treatment (80-85%) do not receive it, Mumola CJ and Kerberg JC. Drug use and dependence, state and federal prisoners, Washington, DC: U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics, 2006.Karberg JC and James DJ. Substance dependence, abuse, and treatment of jail inmates, Washington, DC.: Office of Justice Programs, Bureau of Justice Statistics, 2005.CTN SitesResearch Centers
33 Addictions are brain diseases Human development is keyTreatment can be based on neuroscience advancesPolicies need to account for the nature of addictive disorders
34 Brain and Behavioral Impact of Televised Anti-Tobacco Public Service Announcements: Predictive ValueLeft, dMPFC activation associated with AS by MSV interaction. Statistical map (yellow-red scale) is displayed over the MNI brain template and thresholded at z = 3.1 (cluster corrected at p < 0.001). Right, Correlation between percentage BOLD signal change in dMPFC and predicted cotinine levels at 1 month follow-up, adjusting for the baseline cotinine levels and AS groups.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:
35 Addressing Drugs and Crime Public Health Approach- disease- treatmentPublic Safety Approach- illegal behavior- punishHigh AttritionHigh Recidivism
36 Successful Reentry Programs Use an Integrated Public Health-Public Safety Strategy Close supervisionCommunity-based treatmentBlends functions of criminal justice and treatment systems to optimize outcomesConsequences for noncompliance are certain and immediateOpportunity to avoid incarceration or criminal record
37 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.