Neurobiological Advances in Addiction Science: Implications For Prevention and Treatment Nora D. Volkow, M.D. Director

Transcription

1 Neurobiological Advances in Addiction Science: Implications For Prevention and Treatment Nora D. Volkow, M.D.

2 Drugs and Natural Rewards ACTIVATE Dopamine in Reward Regions % of Basal Release % of Basal Release frontal cortex nucleus accumbens VTA/SN AMPHETAMINE hr Time After Amphetamine 2 FOOD 15 Drugs of abuse increase DA in the Nucleus Accumbens, which is believed to trigger the neuroadaptions that result in addiction 1 5 Empty Box Feeding Time (min) Di Chiara et al.

3 Repeated Drug Use Changes the Brain Weakens the Brain Dopamine System Control Cocaine Abuser T Y R O S I N E T Y R O S I N E T Y R O S I N E DA D O P A DA D O P A DA D O P A COCAINE PLEASURE REPEATED USE OF COCAINE OR OTHER DRUGS REDUCES LEVELS OF DOPAMINE D2 RECEPTORS

4 Bmax/Kd DA D2 Receptors (Ratio Index) Dopamine D2 Receptors are Lower in Addiction 4.5 Normal Controls Cocaine Abusers Cocaine Meth Alcohol 3.2` Heroin control addicted Volkow et al., Neuro Learn Mem

5 John Smith James Smith Ann Jones ThomasSmith AnneCook John Jones Mary Hill John Smith EdwardSmith JaneWalker JamesCook Beth Bryson Walter Jones Alice Price James Hill Susan Edwards John Walker JaneJones JonathanCook Amy Mason Edward Bryson Beth Carter Thomas Jones Rebecca Wilson William Price Alice Benson Richard Hill Mary Walters Steven Adams Susan Adams Allison Fields Addiction Involves Multiple Factors DEVELOPMENT/Genes ENVIRONMENT DRUG Brain Mechanisms Addiction

6 % age group who develop first-time cannabis use disorder The Brain Undergoes Major Changes From Childhood Through Adulthood 1.6% 1.4% 1.2% 1.%.8%.6%.4%.2% Dynamic Sequence of GM Maturation.% Age Age at cannabis use disorder as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 23 Gogtay et al. 24 Proc. Natl. Acad. Sci. USA 11,

7 Social Rank & Vulnerability to Drugs Dominant 3 months Social Deprivation Interferes with Brain Connectivity Social Neglect During Early Childhood Decreases Brain Connectivity Individual Housed Subordinate 3 months Group Housed Individual Housed * * Group Housed Dominant Subordinate 1 S Cocaine (mg/kg/inj) Morgan, D. et al. Nature Neuroscience, 5: , 22. Decreased connectivity between amygdala and OFC wass proportional to time in orphanage. Govindan et al., Cereb Cortex 21.

8 Reduce these Elevate these Prevention Programs Should Enhance Protective Factors & Reduce Risk Factors

9 ADDICTION CAN BE TREATED Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence 3 ml/gm Normal Control METH Abuser (1 month detox) METH Abuser (14 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, , 21.

10 Medications Assisted Therapies Opioid Agonist Treatments Decreased Heroin OD Deaths Baltimore, Maryland, Methadone Promotes Initiation Of Antiretroviral Therapy in IDU Heroin overdoses Buprenorphine patients Methadone patients Schwartz RP et al., Am J Public Health 213. Uhlmann S et al., Addiction 21; 15(5):

11 Around the World WORLD DRUG REPORT 216, UNODC

12 Challenge: How to Integrate Drug Abuse & Addiction Screening, Prevention & Treatment into the Healthcare System

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14 Days Improving Treatments for Addiction: Implementing Medication-Assisted Treatment Emergency department-initiated buprenorphine Reduced self-reported, illicit opioid use Increased engagement in addiction treatment; decreased use of inpatient addiction treatment services Self-Reported Illicit Opioid Use in the Past 7 Days Baseline 3 days Buprenorphine Referral Brief Intervention

15 Childhood Self-Control Predicts Health (Dunedin Study; 1 children) Children with low self-control had poorer health outcomes and higher problems with substance use disorders than those with high self-control Moffitt et al., PNAS 211. Interventions that Aid Executive Function In 4 to 12 Years Olds Self-control can be improved by: Computerized training Non-computerized games Aerobics Martial Arts Yoga Mindfulness School Curricula All successful programs involved repeated practice and progressively increase challenge to executive function Diamond & Lee. Science 211.

16 Medications are Underused In 48 states and D.C., Opioid Abuse and Dependence Rates Exceed Buprenorphine Treatment Capacity In 214, the proportion of opioid admissions with tx plans that included receiving medications was 25% Jones C et al., Am J Public Health 215. Nearly all U.S. states do not have sufficient treatment capacity to provide medication assisted treatment to all patients with an opioid use disorder [VAL UE] MAT [VAL UE] No MAT Treatment Episode Data Set (TEDS):

17 Microstructural Abnormalities in Language and Limbic Pathways in Orphanage-Reared Children: A Diffusion Tensor Imaging Study Relationship between language function and Fractional Anisotropy (FA) for the left arcuate fasciculus in children with early deprivation Increases in FA are associated with better language function Association of mean diffusivity of the left arcuate fasciculus and time spent in the adoptive home Mean diffusivity decreased with increasing time spent in the adoptive environment Kumar A et. al., J Child Neurology 214; 29(3):

18 Duration Of Early Adversity and Structural Brain Development In Post-institutionalized Adolescents Prefrontal gray matter volume (age & sex adjusted) is reduced in PI youth Duration of early adversity predicts hippocampal volume reduction (age and sex adjusted) Duration of adversity over first year of life predicts hippocampal volume (age, sex, and ICV adjusted) in early adolescence (right hippocampal effect is equivalent). Hodel AS et al., Neuroimage. 215 Jan 15;15:

19 Effect of Early Institutionalization and Foster Care on Long-Term White Matter Development Multimodal Regression Models Examining Effects of Intervention Neglect in early life was associated with alterations in white matter microstructure throughout the brain, specifically involving the body of the corpus callosum, cingulum, fornix, anterior and superior corona radiata, external capsule, retrolenticular internal capsule, and medial lemniscus. The foster care group did not significantly differ from the never-institutionalized group in measurements of these tracts, with the exception of the body of the corpus callosum and superior corona radiata. These findings suggest a potential for remediation of specific white matter pathways for children removed from institutional care and placed in responsive families early in life. Bick J et al., JAMA Pediatr 215 Mar; 169(3):

20 Metabolism CG (micromol/1g/min) Metabolism OFC (micromol/1g/min) Frontal Metabolism Metabolism Prefrontal Chronic Drug Use Reduces DA D2 Receptors Impairing Frontal Function DA DA DA DA DA signal DA DA DA D2 Receptors Metabolism Control Controls Controls Cocaine Abuser Methamphetamine Abusers Alcoholics D2R VS (Bmax/Kd) D2 Receptors (BP ND ) D2R VS (Bmax/Kd) D2 Receptors (BP ND ) 3. 4