Drugs and the Brain: Implications for Preventing and Treating Addiction. Nora D. Volkow, M.D. Director National Institute on Drug Abuse

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1 Drugs and the Brain: Implications for Preventing and Treating Addiction Nora D. Volkow, M.D. Director National Institute on Drug Abuse

2 NEUROTOXICITY OBESITY AIDS CANCER MENTAL ILLNESS HEALTH CARE COSTS PRODUCTIVITY LOSS ACCIDENTS HOMELESSNESS CRIME VIOLENCE

3 ADDICTION IS A DISEASE OF THE BRAIN as other diseases it affects the tissue function Decreased Brain Metabolism in Drug Abuse Patient High Control Cocaine Abuser Decreased Heart Metabolism in Heart Disease Patient Low Healthy Heart Diseased Heart Sources: From the laboratories of Drs. N. Volkow and H. Schelbert

4 % in each age group who develop firsttime cannabis use disorder ADDICTION IS A DEVELOPMENTAL DISEASE 1.6% 1.4% 1.2% 1.0% 0.8% 0.6% 0.4% 0.2% 0.0% It starts in adolescence and childhood Age Brain areas where volumes are smaller in adolescents than young adults. Sowell, E.R. et al., Nature Neuroscience, 2: , 1999 Age at cannabis use disorder as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.

5 DRUGS OF ABUSE CAN PRODUCE ADDICTION BY HIJACKING MOTIVATION AND PLEASURE PATHWAYS IN THE BRAIN

6 movement motivation Dopamine addiction Reward & well-being

7 Dopamine Neurotransmission frontal cortex % of Basal Release METHAMPHETAMINE hr Time After Methamphetamine 500 COCAINE nucleus accumbens VTA/SN % of Basal Release hr Time After Cocaine

8 Brain Dopamine System Transporters Receptors Anatomy signal Dopamine Cell Metabolism

9 Dopamine D2 Receptors are Lower in Addiction Cocaine Meth Alcohol D2 Receptor Availability Reward Circuits Non-Drug Abuser Heroin control addicted Reward Circuits Drug Abuser

10 Effects of Tx with an Adenovirus Carrying a D2 Receptor Gene into NAc in D2 Receptors Overexpression of D2 receptors reduces alcohol self-administration Percent Change in D2R % Change in Alcohol Intake st D2R Vector p < p < p < p < nd D2R Vector p < p < Source: Thanos, PK et al., J Neurochem, 78, pp , p < p p < 0.01 < Time (days) Null Vector p < 0.001

11 ADDICTION INVOLVES MULTIPLE FACTORS Biology/Genes Environment DRUG Brain Mechanisms Addiction

12 Effects of a Social Stressor on Brain D2 Receptors and Propensity to Administer Drugs Individually Housed Group Housed Reinforcers (per session) 50 Dominant Subordinate Becomes Dominant No longer stressed * * Becomes Subordinate Stress remains 10 0 Morgan, D. et al. Nature Neuroscience, 5: , S Cocaine (mg/kg/injection)

13 According to the Monitoring the Future Study Methamphetamine is not Increasing * P < th Grade 10th Grade 12th Grade Percent of Students Reporting Use of Methamphetamine in Past Year, by Grade

14 Methamphetamine Treatment Admissions Have Been Increasing Per 100,000 Aged 12 or Older Methamphetamine/Amphetamine Treatment Admission Rate : SAMHSA Treatment Episode Data Set

15 Concerns with Methamphetamine Neurotoxic in animal models of drug self administration Highly addictive Intoxication associated with behaviors that increase risks for infection with HIV and HCV Can be easily manufacturedby small clandestine laboratories

16 Dopamine Transporters in Methamphetamine Abusers Normal Control Methamphetamine Abuser Dopamine Transporters (Bmax/Kd) p < Methamphetamine abusers have significant reductions in dopamine transporters Normal Controls Meth Abusers BNL UCL SUNY

17 Dopamine Transporters in Methamphetamine Abusers Dopamine Transporter (Bmax/Kd) Dopamine Transporter Bmax/Kd Time Gait (seconds) 10 Delayed Recall (words remembered) Motor Task Loss is associated with slowing of motor reactions. Memory Task Loss is associated with memory impairment. BNL/UCLA/SUNY NI, DOE (OBER), ONDCP

18 Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence Normal Control METH Abuser (1 month detox) METH Abuser (24 months detox) ml/gm Source: Volkow, ND et al., Journal of Neuroscience 21, , 2001.

19 70 Proportions of AIDS Cases in Adults and Adolescents by Exposure in the USA % of Cases Injection drug use Men who have sex with men (MSM) Heterosexual contact Year of Diagnosis MSM who injectdrugs Source: Centers for Disease Control and Prevention (CDC)

20 Methamphetamine in the HIV Epidemic METH has been shown to alter immune function Risky sexual behavior that occurs during METH intoxication increases the risk of HIV infection Physiological changes resulting from METH use may increase infectivity (e.g., erosion of normal protective epithelial layer)

21 Aggressive Action Is Needed To Stop METH Use & Its Serious Consequences We Need to Make the Public Aware of the Drug s Toxic and Addictive Properties And todevelop Treatments that will counteract neuroadaptations that underlie the addictive process and reverse METH s neurotoxic effects

22 The Partnership Between NI NATIONAL INSTITUTE ON DRUG ABUSE and Is working to develop A Latin American Epidemiology Work Group that would parallel the US Community Epidemiology Work Group (CEWG) A program offering small research grants to students carrying out their post-graduate thesis work at Latin American Universities