Nora D. Volkow, M.D.Director

@NIDAnews

National Institute on Drug AbuseNational Institutes of Health

How Drugs Affect

the Brain

Brain Circuits Involved in the Addiction Cycle

Koob and Volkow, Lancet Psychiatry 2016.

Addiction Involves Multiple Factors

Addiction

DRUG

Brain Mechanisms

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(%)

Age at first use (years)10 20 30

TOBACCO

10 20 30

ALCOHOL

10 20 30 40

CANNABIS100

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80

70

60

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Adolescence is the period of greater vulnerability for drug use and addiction

Degenhardt, JAMA Psychiatry 2016.

Role Of Genetics On Brain Development

•Highest heritability in evolutionarily novel regions (temporal poles, inferior parietal lobes, and superior and dorsolateral frontal cortices)

•Heritability increased through late childhood and adolescence.

Schmitt et al., Proc Natl Acad Sci U S A. 2014 111(18): 6774–6779.

Social and Emotional Deprivation Increases Risk For SUD and Mental Illnesses

Decreases in brain connectivity with social neglect in childhood

Decreases in connectivity were proportional to time in orphanage

Govindan et al., Cereb Cortex 2010 Mar;20(3): 561-569.

Early (<18y) Long-Term Cannabis Use Decreases Connectivity

Reduced connectivity (measured with MRI) in cannabis users (n=59) compared to controls (N=33).

Zalesky et al Brain 2012.

Early Drug Use Can Modify Brain Development

Lower Hippocampal Synaptic Density In Cannabis Use Disorder

[11C]UCB-J BPND in Cannabis Use Disorder (CUD) and Healthy Controls (HC)

D’Souza, CD et al., Molecular Psychiatry, online September 24 2020.

Imaging of TSPO (Neuroinflammation Marker)in Long-term Cannabis Users[18F]FEPPA Distribution Volume in

Cannabis Users

Da Silva T et al., JAMA Psychiatry 2019;76(12):1306-1313.

TYROSINE

DA

DOPA

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Acutely, Drugs Increase Dopamine but Repeated Use Decreases it

TYROSINE

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COCAINE

TYROSINE

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Control Cocaine Misuse

PLEASURE

Repeated Drug Use Modifies Brain Chemistry & Function

Dopamine Receptor Over-Expression in Alcohol-Preferring Rats

Over-expression of D2 receptors in rats markedly reduces alcohol intake

0102030405060

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DA D2 Levels

Thanos et al., Alcohol Clin Exp Res. 2004.

Thanos, PK et al., J Neurochem, 2001.

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Cocaine (mg/kg/inj)

DominantSubordinate

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

Social Rank & Vulnerability to Drug Use

3 months

Dominant

Group Housed

IndividualHoused

Subordinate3 months

Individual Housed

GroupHoused

Early Aggressive BehaviorPoor Social SkillsLack of Parental SupervisionSubstance UseDrug AvailabilityPoverty

RISK

Self ControlParental Monitoring & SupportPositive RelationshipsAcademic CompetenceAnti-Drug Use Policies

Strong Neighborhood

PROTECTION

IndividualFamilyPeer

SchoolCommunity

Protective Effects of a Supportive Parenting Intervention (SAAF n=59) on Poverty’s Effects on Brain Development (Control n=57)

Strong African American Families (SAAF)

Brody GH et al. JAMA Pediatr. 2017;171(1):46-52.

Brody GH et al., J Child Psychology Psychiatry. 2019 60(1):63-71.

Preventive Parenting Intervention (SAAF n=290) During Childhood and Young Black Adults' Unhealthful Behaviors (Control n=219)

Normal Control Methamphetamine(2x-1 month detox)

Methamphetamine(9 months detox)

Recovery of Brain Dopamine Transporters After Protracted Abstinence following Methamphetamine Misuse

Drug Use Can be Treated

Volkow et al., Mol Psychiatry 2015

1.5

DVR2.2

Intersection Between Opioid Crisis and COVID-19

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Overdoses Grew Dramatically During COVID Pandemic

ST

Total Study Population Change in Unadjusted Positivity Rate for Cocaine, Fentanyl, Heroin and Methamphetamine

31.96%

19.96%

10.06%12.52%

Total US Increase

Drug Use Increase During COVID

Millennium Health Signals Report™ COVID-19 Special Edition: Significant Changes in Drug Use During the Pandemic Volume 2.1 Published July 2020

Social Interaction Favored over Heroin Unless Social Interaction is Punished

Venniro et al., Nature Neuroscience 2018

Resident self-administration

chamber

Partner chamber

Social leverDrug lever

Slidingdoor

HEROIN