Addiction: It’s a Brain Disease Beyond a Reasonable DoubtPresentation Objectives•Identify impact of substance abuse & addiction•Examine contribution of nature vs. nurture•Explain how drugs “work”•Understand how prolonged drug use changes brain circuitry•Understand how appropriate treatment can help people recover from drug abuse and addiction.NEUROTOXICITYAIDSCANCERMENTAL ILLNESSNeurotoxicityAIDS, CancerMental illnessHealth careProductivityAccidentsHomelessnessCrimeViolenceEstimated Economic Cost to Society from Substance Abuse and Addiction:Illegal drugs: $181 billion/yearAlcohol: $185 billion/yearTobacco: $158 billion/yearTotal: $524 billion/yearSurgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000. Contributors to the Economic Costs of Substance Abuse and Addiction•Health care expenditures–Alcohol and drug abuse services–Medical consequences•Productivity (lost earnings)–Premature death–Impaired job performance–Institutionalized population–Incarceration–Criminal victimization•Other impacts on society–Crime–Social welfare administration–Vehicular accidentsAdapted from Harwood et al., Addiction, 1999.Between 50% and 80% of Adult Male Arrestees Tested Positive for Illicit Drug Use in 2000 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Albany Albuquerque Anchorage Atlanta Chicago Cleveland Dallas Denver Detroit Honolulu Indianapolis Miami New Orleans New York Philadelphia Phoenix Portland Sacramento San Antonio San Diego San Jose Seattle Spokane Tuscon Drug Use Correlates with Crime 2000 Arrestee Drug Abuse Monitoring: Annual Report, April 2003. •More than 50% of violent crimes •60-80% of child abuse and neglect cases •50-70% of theft and property crimes•75% of drug dealingBelenko and Peugh, 1998; National Institute of Justice, 1999.The Perpetrator is Involved in Drug Use in…However…advances in science have revolutionized our fundamental views of drug abuse and addiction, showing us that:►abuse is a preventable behavior►addiction is a treatable diseaseused to beYour Brain on Drugs Today1-2 Min3-45-66-77-88-99-1010-2020-30YELLOW shows places in brain where cocaine goes (striatum)Front of BrainBack of BrainFowler et al., Synapse, 1989.Common Myths About Drug Abuse…•Drug abuse equates to drug addiction•Alcohol is not a drug•Addiction is a moral weakness•You have to hit rock bottom to recover•You have to want treatment for it to be successful•Drug abuse is more common among minoritiesWhat is Addiction?•A brain disease expressed as a compulsive behavior •The continued abuse of drugs despite negative consequences •A chronic, potentially relapsing disorderWhy Do People Take Drugs in The First Place?To feel goodTo have novel:feelingssensationsexperiencesANDto share themTo feel betterTo lessen:anxietyworriesfearsdepressionhopelessnessWhy do some people become addicted while others do not? VulnerabilityWe Know There’s aBig Genetic Contribution toDrug Abuse and Addiction…….Overlapping with Environmental Influences that Help Make Addiction a Complex Disease.Biology/genesEnvironmentBiology/EnvironmentInteractionshighlowHigh DA receptorLow DA receptorDA Receptors and the Response to Methylphenidate (MP)As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasantAdapted from Volkow et al., Am. J. Psychiatry, 1999.Dopamine receptor level Drug Abuse Drug/Alcohol Related Traffic Accidents DelinquencyAcademic Failure and DroppingOut of SchoolJuvenile DepressionSexually Transmitted Diseases (Including HIV/AIDS) Running Away From HomeUnwanted Pregnancies Suicidal Behavior CommunityPeer ClusterFamilyIndividualHow Do Drugs “Work”?Initially, a person takes a drug hoping to change his or her mood, perception, or emotional stateTranslation –…hoping to change their brains.We know that despitetheir many differences, most abused substances enhance the dopamine and serotonin pathwaysBasolateral AmygdalaPrefrontal CortexMediodorsal ThalamusMotor NucleiVentral PallidumNucleus AccumbensVentral Tegmental AreaGABA and Glutamate Role in MotivationAdapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.DopamineGlutamateGABACircuits Involved In Drug Abuse and AddictionAll of these must be consideredin developing strategies to effectively treat addiction Alcohol vs. Other DrugsWe know that alcohol impairs the brain and results in addiction with repeated use in the same way as other drugs StorageSynthesisPrecursorReleaseReuptakeDegradationSynaptic Cleft= vesicle= neurotransmitters= receptordopamine transporters050100150200060120180Time (min)% of Basal DA OutputNAc shellEmptyBoxFeedingDi Chiara et al., Neuroscience, 1999.FOODMountsIntromissionsEjaculationsFiorino and Phillips, J. Neuroscience, 1997.Natural Rewards Elevate Dopamine Levels100150200DA Concentration (% Baseline)150510Copulation FrequencySampleNumber12345678SEXFemale Present010020030040050060070080090010001100012345 hrTime After Amphetamine% of Basal ReleaseDADOPACHVAAccumbensAMPHETAMINE0100200300400012345 hrTime After Cocaine% of Basal ReleaseDADOPACHVAAccumbensCOCAINE0100150200250012345hrTime After Morphine% of Basal ReleaseAccumbens0.51.02.510Dose (mg/kg)MORPHINE01001502002500123 hrTime After Nicotine% of Basal ReleaseAccumbensCaudateNICOTINEDi Chiara and Imperato, PNAS, 1988Effects of Drugs on Dopamine Releaseprolonged drug use changesthe brain in fundamentaland long-lasting waysScience has generated muchevidence showing that…Control Addicted Cocaine Alcohol DA DA DA DA DA DA Reward Circuits DA DA DA DA DA Reward Circuits DA DA DA DA DA DA Drug Abuser Non-Drug Abuser Heroin Meth Dopamine D2 Receptors are Lower in Addiction DADopamine Transporters in Methamphetamine AbusersNormal ControlMethamphetamine AbuserMotor TaskLoss of dopamine transporters in the meth abusers may result in slowing of motor reactions.Memory taskLoss of dopamine transporters in the meth abusers may result in memory impairment.789101112131.01.21.41.61.82.0Time Gait(seconds)468101214161.01.21.41.61.82.0Delayed Recall(words remembered)Dopamine TransporterBmax/Kd Volkow et al., Am. J. Psychiatry, 2001..Implication:Brain changes resulting from prolonged use of drugs may compromise mental and motor functionsNature Video Cocaine VideoConditionedAssociation1.50.51.02.02.5CRAVING INDUCTION IN A PET SETTINGN = 13DCRAVING543210-1NeutralCocaineSTIMULIChildress et al., Am. J. Psychiatry, 1999Memories Appear to Be A Critical Part of Addiction“Its about people, places and things…”Cocaine Film Cocaine Craving: Population (Cocaine Users, Controls) x Film (cocaine, erotic) Garavan et al., Am. J. Psychiatry, 2000. IFG Ant. Cing. Cingulate Signal Intensity (AU) Cocaine Erotic Film Controls Cocaine UsersDrugs Are Usurping Brain Circuitsand Motivational PrioritiesTreatment and the Cycle of AddictionAddiction is the Quintessential Biobehavioral DisorderDrugsBrain MechanismsBehaviorEnvironmentHistoricalEnvironmental-Prior experience-Expectation-Learning-Social interactions-Stress-Conditioned stimuli-Genetics-Circadian rhythms-Disease states-GenderPhysiologicalDrug Addiction: A Complex Behavioral and Neurobiological DisorderSource: Adapted from Volkow et al., Neuropharmacology, 2004.DriveSaliencyMemoryControlNon-Addicted BrainNOT GOAddicted BrainDriveMemoryControlGOSaliency Addiction Changes Brain CircuitsThis is why treatment is essentialThis is why addicts can’t just quitTreating a Biobehavioral Disorder Must Go Beyond JustFixing the Chemistry•Pharmacological (medications)•Behavioral Therapies•Medical and Social ServicesWe Need to Treat theWhole Person!In Social ContextTreatment Can WorkBut, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthmaMcLellan et al., JAMA, 2000. Relapse Rates Are Similar for Drug Addiction & Other Chronic IllnessesDrug AddictionType I Diabetes0102030405060708090100HypertensionAsthma40 to 60%30 to 50%50 to 70%50 to 70%Percent of Patients Who RelapseMcLellan et al., JAMA, 2000. Addiction is Similar to Other Chronic Illnesses Because:•Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated treatments•Relapses to drug abuse can occur during or after successful treatment episodes•Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recoveryTherefore…012345678 Pre During Post Hypertension Tx Stage of Tx YES 012345678 Pre During Post Addiction Tx Stage of Tx NO There is a right way and a wrong way to Measure the Outcome of Treating Chronic Illnesses like AddictionFull recovery is a challenge but it is possible …DAT Recovery with prolonged abstinence from methamphetamine [C-11]d-threo-methylphenidate Volkow et al., J. Neuroscience, 2001. low high Normal Control Methamphetamine Abuser (1 month detoxification) Methamphetamine Abuser (24 month abstinent) Treatment Reduces Drug Use and RecidivismDelaware Work Release Therapeutic Community (CREST) + Aftercare3 Years After Release (N=448)p < 0.05, compared to No Treatment groupPercentage of ParticipantsDrug-FreeArrest-FreeWe Need to Keep Our Eye onthe Real TargetIn Treating Addiction…Since it was established in 1974, NIDA has supported research on drug abuse treatment for individuals who are involved with the criminal justice system.Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000. Adapted from Harwood et al., Addiction, 1999.2000 Arrestee Drug Abuse Monitoring: Annual Report, April 2003. Belenko and Peugh, 1998; National Institute of Justice, 1999.Fowler et al., Synapse, 1989.Adapted from Volkow et al., Am. J. Psychiatry, 1999.Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.Di Chiara et al., Neuroscience, 1999.Fiorino and Phillips, J. Neuroscience, 1997.Di Chiara and Imperato, PNAS, 1988Volkow et al., Am. J. Psychiatry, 2001Garavan et al., Am. J. Psychiatry, 2000.Childress et al., Am. J. Psychiatry, 1999.Source: Adapted from Volkow et al., Neuropharmacology, 2004.McLellan et al., JAMA, 2000. McLellan et al., JAMA, 2000. Volkow et al., J. Neuroscience, 2001.We want to thank TASC, Inc., of Illinois for their contribution to this presentation.