Neurobiological Advances in Addiction Science:

Implications For Prevention and Treatment

Nora D. Volkow, M.D.

Director

@NIDAnews

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Di Chiara et al.

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nucleus accumbens

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Drugs of abuse increase DA in the Nucleus

Accumbens, which is believed to trigger the

neuroadaptions that result in addiction

Drugs and Natural Rewards ACTIVATE

Dopamine in Reward Regions

Repeated Drug Use Changes the Brain Weakens the Brain Dopamine System

T Y R O S I N E

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REPEATED USE OF COCAINE OR OTHER DRUGS REDUCES LEVELS OF DOPAMINE D2 RECEPTORS

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PLEASURE

Dopamine D2 Receptors are Lower in Addiction

Cocaine

Alcohol

Heroin

Meth

control addicted Volkow et al., Neuro Learn Mem 2002.

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Addiction Involves Multiple Factors

Addiction

DRUG

Brain Mechanisms

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ENVIRONMENT

Gogtay et al. 2004 Proc. Natl. Acad. Sci. USA 101, 8174-8179.

Dynamic Sequence of GM Maturation

The Brain Undergoes Major Changes From Childhood Through Adulthood

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Age Age at cannabis use disorder as per DSM IV

NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003

Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002.

Social Rank & Vulnerability to Drugs

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Dominant

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Individual Housed

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Group Housed

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Dominant Subordinate

Social Deprivation Interferes with Brain Connectivity

Social Neglect During Early Childhood

Decreases Brain Connectivity

Decreased connectivity between amygdala and OFC wass proportional to time in orphanage.

Govindan et al., Cereb Cortex 2010.

Prevention Programs Should Enhance Protective Factors & Reduce Risk Factors

Reduce these Elevate these

Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH)

Abuser After Protracted Abstinence

Normal Control METH Abuser (1 month detox)

METH Abuser (14 months detox)

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Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

ADDICTION CAN BE TREATED

Opioid Agonist Treatments

Decreased Heroin OD Deaths Baltimore, Maryland, 1995-2009

Heroin overdoses

Buprenorphine patients

Methadone patients

Schwartz RP et al., Am J Public Health 2013.

Medications Assisted Therapies

Methadone Promotes Initiation

Of Antiretroviral Therapy in IDU

Uhlmann S et al., Addiction 2010; 105(5):907-913.

WORLD DRUG REPORT 2016, UNODC

Around the World…

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

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Buprenorphine Referral Brief Intervention

Baseline 30 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

Da

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Self-Reported Illicit Opioid Use in the Past 7 Days

Children with low self-control had poorer health outcomes and higher problems with substance use disorders than those with high self-control

Childhood Self-Control Predicts Health

(Dunedin Study; 1000 children)

Moffitt et al., PNAS 2011.

Self-control can be improved by: • Computerized training • Non-computerized games • Aerobics • Martial Arts • Yoga • Mindfulness • School Curricula

Interventions that Aid Executive Function In

4 to 12 Years Olds

All successful programs involved repeated practice and progressively increase challenge to executive function

Diamond & Lee. Science 2011.

Medications are Underused

Nearly all U.S. states do not have sufficient treatment capacity to provide medication assisted treatment to all patients with an opioid use disorder

[VALUE]

[VALUE]

MAT No MAT

In 2014, the proportion of opioid

admissions with tx plans that

included receiving medications

was 25%

Treatment Episode Data Set (TEDS): 2004-2014.

Jones C et al., Am J Public Health 2015.

In 48 states and D.C., Opioid Abuse

and Dependence Rates Exceed

Buprenorphine Treatment Capacity

Microstructural Abnormalities in Language and Limbic

Pathways in Orphanage-Reared Children:

A Diffusion Tensor Imaging Study

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

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

Kumar A et. al., J Child Neurology 2014; 29(3): 318-325.

Duration Of Early Adversity and Structural Brain

Development In Post-institutionalized Adolescents

Hodel AS et al., Neuroimage. 2015 Jan 15;105:112-119.

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).

• 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.

Effect of Early Institutionalization and Foster Care on

Long-Term White Matter Development

Bick J et al., JAMA Pediatr 2015 Mar; 169(3): 211-219.

Multimodal Regression Models Examining Effects of Intervention

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Chronic Drug Use Reduces DA D2

Receptors Impairing Frontal

Function

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