Neurotoxicity AIDS, Cancer Mental illness Homelessness Health care Crime Productivity Violence Accidents
4 Out of 10 U.S. AIDS Deaths Are Related to Drug Abuse
Estimated Economic Cost to Society Due to Substance Abuse and Addiction: Illegal drugs: $181 billion/year Alcohol: $185 billion/year Tobacco: $158 billion/year Total: $524 billion/year Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000.
What is Addiction? Addiction is A Brain Disease • Characterized by: – Compulsive Behavior – Continued abuse of drugs despite negative consequences – Persistent changes in the brain’s structure and function
Advances in science have revolutionized our fundamental views of drug abuse and addiction.
Your Brain on Drugs in the 1980’s
Your Brain on Drugs Today YELLOW shows places in brain where cocaine binds (e.g., striatum) Fowler et al., Synapse, 1989.
Addiction is Like Other Diseases… It is preventable It is treatable It changes biology If untreated, it can last a lifetime Decreased Brain Metabolism Decreased Heart Metabolism in Drug Abuser in Heart Disease Patient High Low Healthy Brain Diseased Brain/ Healthy Diseased Heart Cocaine Abuser Heart Research supported by NIDA addresses all of these components of addiction.
Addiction Involves Multiple Factors
Addiction Is A Developmental Disease that starts in adolescence and childhood 1.8% .8% ce TOBACCO o 1.6% .6% h en CANNABIS d w ALCOHOL 1.4% .4% p en ep 1.2% .2% e d 1.0% .0% 0.8% .8% age grou 0.6% .6% each first-tim 0.4% .4% in 0.2% .2% % evelop d 0.0% .0% 5 10 15 15 21 21 25 25 30 30 35 35 40 40 45 45 50 55 55 60 60 65 Age Age at tobacco, alcohol, and cannabis dependence per DSM IV National Epidemiologic Survey on Alcohol and Related Conditions, 2003.
Why Do People Take Drugs in The First Place? To Feel Good To Feel Better To have novel: To lessen: feelings anxiety sensations worries experiences fears AND depression to share them hopelessness
Why Do People Abuse Drugs? Drugs of Abuse Engage Motivation and Pleasure Pathways of the Brain
Drugs can be “Imposters” of Brain Messages
Movement Motivation Dopamine Addiction Reward & well-being
The Neuron: How the Brain’s Messaging System Works Dendrites Cell body Axon (the cell’s life support center) Terminal branches of axon Neuronal Impulse Myelin sheath Donald Bliss, MAPB, Medical Illustration
Natural Rewards Elevate Dopamine Levels Food Sex 200 e) 200 t NAc shell u aselin tp 150 B u 150 O (% A 100 100 asal D tration cen of B Empty 50 on % Box Feeding C A D Female Present 0 0 60 120 180 Sample 1 2 3 4 5 6 7 8 Time (min) Number Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997.
Effects of Drugs on Dopamine Release Amphetamine Cocaine 1100 Accumbens 400 Accumbens 1000 900 800 300 elease DA DOPAC elease DA 700 HVA DOPAC 600 HVA 200 500 asal R asal R 400 300 100 of B of B 200 % 100 % 0 0 0 1 2 3 4 5 hr 0 1 2 3 4 5 hr 250 Morphine Nicotine 250 Accumbens Dose 200 200 0.5 mg/kg 1.0 mg/kg 150 elease Accumbens Caudate elease 2.5mg/kg 150 10 mg/kg 100 asal R asal R 100 of B of B 0 % % 0 1 2 3 hr 0 0 1 2 3 4 5 hr Time After Drug Time After Drug Di Chiara and Imperato, PNAS, 1988
But Dopamine is only Part of the Story • Scientific research has shown that other neurotransmitter systems are also affected: – Serotonin –Regulates mood, sleep, etc. – Glutamate –Regulates learning and memory, etc.
Science Has Generated Much Evidence Showing That… Prolonged Drug Use Changes the Brain In Fundamental and Long-Lasting Ways
AND… We Have Evidence That These Changes Can Be Both Structural and Functional
Structurally… Neuronal Dendrites in the Nucleus Accumbens Saline Amph Robinson & Kolb, Journal of Neuroscience, Volume: 1997
Functionally… Dopamine D2 Receptors are Decreased by Addiction Cocaine ytilibaliav Meth A rotpeceR 2 Alcohol D AD Heroin Control Addicted
Dopamine Transporters in Methamphetamine Abusers 2.0 Motor Task 1.8 Loss of dopamine transporters in 1.6 methamphetamine 1.4 abusers may result in slowing of motor 1.2 orter
reactions. sp d 1.07 8 9 10 11 12 13 ran ax/K Time Gait e T m (seconds) Normal Control in B 2.0 am Memory Task op Loss of dopamine 1.8 D transporters in 1.6 methamphetamine 1.4 abusers may result in memory impairment. 1.2 1.016 14 12 10 8 6 4 Delayed Recall (words remembered) Methamphetamine Abuser Volkow et al., Am. J. Psychiatry, 2001.
Implication? Brain changes resulting from prolonged use of drugs may compromise mental AND motor function.
Circuits Involved In Drug Abuse and Addiction All of these brain regions must be considered in developing strategies to effectively treat addiction
Priority Areas for NIDA Prevention Research (Children & Adolescents) genetics environment development co-morbidity Treatment Research (New Targets & New Strategies) HIV/AIDS Research
Addiction is a Developmental Disease: It Starts Early 67% 26% )ste itia f In t o n e rc e 5.5% , (P se U a n a riju a 1.5% irst M F <12 12-17 18-25 >25
Basic Science Tells Us that Adolescents’ Brains Are Still Developing…
When Reading Emotion… Adults Rely More on the Frontal Cortex While Teens Rely More on the Amygdala Deborah Yurgelon-Todd 2000.
Do Adolescents React Differently than Adults to Substances of Abuse?
Rats Exposed to Nicotine in Adolescence Self-Administer More Nicotine Than Rats First Exposed as Adults Collins et al, Neuropharmacology, 2004, Levin et al, Psychopharmacology, 2003
Do We Need Fundamentally Different Strategies At Different Stages of Adolescence?
Vu V lnerability Why do some people become addicted to drugs while others do not?
Individual Differences in Response to Drugs: DA Receptors influence drug liking High DA high receptor Low DA receptor low As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999.
Genetics is a Big Contributor to the Risk of Addiction… And… The Nature of this Contribution Is Extremely Complex
Gene Cluster is Associated with Nicotine Dependence
What Other Biological Factors Contribute to Addiction--Comorbidity Prevalence of Drug Disorders Prevalence of 40 Nicotine Addiction 35 80 30 60 25 20 ercent ercent P 40 P 15 10 20 5 0 0 ania Depression ood Disorder eneral public General public G Schizophrenia Any MAny Anxiety Disorder Depression M Panic w/ Agoraphobia Panic w/out Agoraphobia Social Phobia Generalized Anxiety
Why do Mental Illnesses and Substance Abuse Co-occur? • Self-medication – substance abuse begins as a means to alleviate symptoms of mental illness • Causal effects – Substance abuse may increase vulnerability to mental illness • Common or correlated causes – the risk factors that give rise to mental illness and substance abuse may be related or overlap
What Environmental Factors Contribute to Addiction? • Stress • Early physical or sexual abuse • Witnessing violence • Peers who use drugs • Drug availability
Social Stressor Affects Brain DA D2 Receptors and Drug Self-Administration Individually Group Housed Housed ) 50 Subordinate n Dominant Becomes Dominant ois 40 No longer stressed ses rep 30( s * r * ec 20 rofn 10 Becomes Subordinate ie Stress remains R 0 S.003 .01 .03 .1 Cocaine (mg/kg/injection) Morgan, D. et al., Nature Neuroscience, 2002.
Prevention Works: Knowledge of Risk and Protective Factors Has Led to the Development of Effective Prevention Strategies
Changes in Attitudes Lead to Changes in Use Monitoring the Future Study, 2007.
Priority Areas for NIDA Prevent r ion Research ( r Children & dr Adolescents) genetics environ r ment development co-morbidity Treatment Research (New Targets & New Strategies) HIV/AIDS Researc sear h
Why Can’t Addicts Just Quit? Non-Addicted Brain Addicted Brain Control Control Saliency Drive GO Saliency Drive NO GO Memory Memory Because Addiction Changes Brain Circuits Adapted from Volkow et al., Neuropharmacology, 2004.
This is why addicts can’t just quit. and… This is why treatment is essential.
Treating a Biobehavioral Disorder Must Go Beyond Just Fixing the Chemistry We W Need to Tr T eat the Whole Person! Pharmacological Behavioral Therapies Treatments (Medications) Medical Services Social Services In Social Context
Treatment Can Work! NIDA’s Principles of Treatment • No single treatment is appropriate for all individuals. • Treatment needs to be readily available. • Treatment must attend to multiple needs of the individual, not just drug use. • Multiple courses of treatment may be required for success. • Remaining in treatment for an adequate period of time is critical for treatment effectiveness.
We Are Using Science to Develop Even Better Treatments Genetics Mechanisms Treatments
Basic Research Medication Agonist Therapy Opiate agonists stabilize brain Methadone function in heroin addicts Buprenorphine CB1 KO mice have decreased CB1 Antagonists responses to multiple drugs of abuse Smokers who are poor nicotine Inhibitors of metabolizers smoke less metabolizing enzymes Stress triggers relapse in animal models of addiction and CRF antagonists CRF Antagonists interfere with the response to stress
But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma. McLellan et al., JAMA, 2000.
Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses 100 se 90 elap 80 o R h 70 60 ts W 50 atien 40 30 t of P 20 ercen 10 40 to 60% 30 to 50% 50 to 70% 50 to 70% P 0 Drug Type I Hypertension Asthma Addiction Diabetes McLellan et al., JAMA, 2000.
Addiction is Similar to Other Chronic Illnesses Because: • It has biological and behavioral components, both of which must be addressed during treatment. • Recovery from it--protracted abstinence and restored functioning--is often a long-term process requiring repeated episodes of treatment. • Relapses can occur during or after treatment, and signal a need for treatment adjustment or reinstatement. • Participation in support programs during and following treatment can be helpful in sustaining long-term recovery
Full recovery is a challenge but it is possible …
Extended Abstinence is Predictive of Sustained Recovery After 5 years – if you are sober, you probably will stay that way. It takes a year of abstinence before less than half relapse Dennis et al, Eval Rev, 2007
[C-11]d-threo-methylphenidate DAT Recovery Normal Control with prolonged high abstinence from methamphetamine Methamphetamine Abuser (1 month abstinent) low Methamphetamine Abuser (14 months abstinent) Volkow et al., J. Neuroscience, 2001.
Treatment Reduces Drug Use and Recidivism Delaware Work Release Therapeutic Community (CREST) + Aftercare 3 Years After Release (N=448) p < 0.05, compared to no treatment group ts
an articip tage of P ercen P ent ent pleters pleters pleters pleters No treatm CREST Dropouts CREST Dropouts CREST ComCREST Com CREST ComCREST Com + Aftercare No treatm + Aftercare
In Treating Addiction… We W Need to Keep Our Eye on the Real Tar T gets! Abstinence Functionality in Family, Work and Community
Priority Areas for NIDA Pre r vention Researc esear h (Childre dr n & Adolescents) genetics environ r ment development co-morbidity Tr T eat r ment Research esear (New T ar T gets & New Strategies) HIV/AIDS Research
Drug Use Has Played a Prominent Role in the HIV/AIDS Epidemic In Several Ways • Disease Transmission - IV Drug Use—Needle sharing - Drug Intoxication: Impaired judgment, disinhibition, leading to risky sexual behaviors • Disease Progression • Neurological Complications
Drugs of Abuse Have Had A Major Impact on the HIV/AIDS Epidemic Proportions of AIDS Cases in Adults & Adolescents by 70 Exposure in the USA 60 50 Men who have sex with men (MSM) ases 40 Injection drug use of C 30 % 20 Heterosexual contact MSM who inject drugs 10 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 Year of Diagnosis Centers for Disease Control and Prevention (CDC)
Convergence of HIV Seroprevalence Among Injecting and Non-injecting Drug Users Drug Treatment Program Respondent-Driven Sampling (n=2121 2001-2004) (n=448 2004) 20 20 17% ce 15% CI 12-21% 15 13% 12% 15 CI 11-19% CI 12-15% CI 9-16% revalen P10 10 IV H 5 5 0 0 Current Injectors Non-Injectors Current Injectors Non-Injectors Source: Des Jarlais et al AIDS, 21: 231-235, 2007.
The AIDS Epidemic Disproportionately Affects Minority Populations 70 White, not Hispanic 60 50 Black, not Hispanic ases 40 Hispanic 30 of C % 20 Asian/Pacific Islander American Indian/ 10 Alaska Native 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 Year of Diagnosis Centers for Disease Control and Prevention (CDC)
Acceleration of HIV Degeneration of Dopamine Cells With Cocaine
NIDA International Program Components Post-Doctoral Research Fellowship Technical International Scientific Consultation Research Exchange Collaboration Information Dissemination
Why focus on drug abuse internationally? I. Drug abuse is a global phenomenon 5 % of people aged 15-64 II. Intertwined dual-epidemics of drug addiction & HIV/AIDS HIV Infections Attributed to Injection Drug Use and Risky UNODC 2005 World Drug Report Sexual Behaviors Related to Drug Abuse III. Take advantage of unique opportunities to advance scientific knowledge through research
NIDA Supports International Drug Abuse Research In Numerous Ways Fund international research Provide training and exchange opportunities Set international research priorities Organize & sponsor conferences and meetings Binational agreements Dissemination of information
Where Do We Need to Go From Here? We Need to… Advance the SCIENCE and… d… Erase th ase e STIGMA