Understanding Addiction and Its Impact on the Brain. SDSMA Webinar Matthew Stanley, DO

Understanding Addiction and Its Impact on the Brain SDSMA Webinar Matthew Stanley, DO

Estimated Economic Cost to Society Due to Substance Abuse and Addiction: Illegal drugs: Alcohol: Tobacco: $181 billion/year $185 billion/year $158 billion/year Total: $524 billion/year Surgeon General s Report, 2004; ONDCP, 2004; Harwood, 2000.

25,000 National Overdose Deaths Number of Deaths from Prescription Drugs Total Female Male 20,000 15,000 10,000 5,000 0 Source: National Center for Health Statistics, CDC Wonder

16,000 14,000 12,000 10,000 8,000 6,000 4,000 2,000 0 National Overdose Deaths Number of Deaths from Rx Opioid Pain Relievers 18,000 Total Female Male Source: National Center for Health Statistics, CDC Wonder

9,000 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000 0 National Overdose Deaths Number of Deaths from Heroin Total Female Male Source: National Center for Health Statistics, CDC Wonder

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 in Drug Abuser High Decreased Heart Metabolism in Heart Disease Patient Healthy Brain Diseased Brain/ Cocaine Abuser Low Healthy Heart Diseased Heart Research supported by NIDA addresses all of these components of addiction.

Addiction Involves Multiple Factors

% in each age group who develop first-time dependence Addiction Is A Developmental Disease that starts in adolescence and childhood 1.8% 1.6% 1.4% 1.2% 1.0% 0.8% 0.6% 0.4% 0.2% TOBACCO CANNABIS ALCOHOL 0.0% 5 10 15 21 25 30 35 40 45 50 55 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 have novel: feelings sensations experiences AND to share them To Feel Better To lessen: anxiety worries fears depression hopelessness

Why Do People Abuse Drugs? Drugs of Abuse Engage Motivation and Pleasure Pathways of the Brain

dopamine transporters

% of Basal DA Output DA Concentration (% Baseline) Natural Rewards Elevate Dopamine Levels 200 Food NAc shell 200 Sex 150 150 100 100 50 Empty Box Feeding 0 0 60 120 180 Time (min) Sample Number Female Present 1 2 3 4 5 6 7 8 Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997.

% of Basal Release % of Basal Release % of Basal Release % of Basal Release Effects of Drugs on Dopamine Release 1100 1000 900 800 700 600 500 400 300 200 100 0 250 200 150 Amphetamine Accumbens DA DOPAC HVA 0 1 2 3 4 5 hr Nicotine Accumbens Caudate 400 300 200 100 0 250 200 150 Accumbens Cocaine DA DOPAC HVA 0 1 2 3 4 5 hr Accumbens Morphine Dose 0.5 1.0 2.5 10 mg/kg mg/kg mg/kg mg/kg 100 100 0 0 1 2 3 hr Time After Drug Di Chiara and Imperato, PNAS, 1988 0 0 1 2 3 4 5 hr Time After Drug

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 Meth Alcohol Heroin Control Addicted

Drugs Have Long-term Consequences Photo courtesy of NIDA from research conducted by Melega WP, Raleigh MJ, Stout DB, Lacan C, Huang SC, Phelps ME.

Dopamine Transporter Bmax/Kd Dopamine Transporters in Methamphetamine Abusers Normal Control Methamphetamine Abuser 2.0 1.8 1.6 1.4 1.2 1.0 7 8 9 10 11 12 13 2.0 1.8 1.6 1.4 1.2 1.0 16 14 Time Gait (seconds) 12 10 8 6 Delayed Recall (words remembered) Volkow et al., Am. J. Psychiatry, 2001. 4 Motor Task Loss of dopamine transporters in methamphetamine abusers may result in slowing of motor reactions. Memory Task Loss of dopamine transporters in methamphetamine abusers may result in memory impairment.

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

Photo courtesy of the NIDA Web site. From A Slide Teaching Packet: The Brain and the Actions of Cocaine, Opiates, and Marijuana.

Addiction is a Developmental Disease: 100 It Starts Early 67% 26% 10 5.5% 1.5% 1 Child Teen Young Adult Adult <12 12-17 18-25 >25

MRI Scans of Healthy Children and Teens Over Time Copyright 2004 by the National Academy of Sciences Gogtay, Giedd, et al. Proc. Natl. Acad. Sci., 2004

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

Vulnerability 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 receptor high 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

Percent What Other Biological Factors Contribute to Addiction--Comorbidity Percent 40 Prevalence of Drug Disorders Prevalence of Nicotine Addiction 35 30 25 20 15 10 5 0 80 60 40 20 0

COMORBIDITY

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 Housed Becomes Dominant No longer stressed Group Housed 50 40 Subordinate Dominant 30 20 * * Becomes Subordinate Stress remains 10 0 S.003.01.03.1 Cocaine (mg/kg/injection) Morgan, D. et al., Nature Neuroscience, 2002.

Changes in Attitudes Lead to Changes in Use 60 50 40 30 20 10 0 75 77 79 81 83 85 87 89 91 93 95 97 99 01 03 05 07 Past Year Use Perceived Risk Monitoring the Future Study, 2007.

Why Can t Addicts Just Quit? Non-Addicted Brain Control Addicted Brain Control Saliency Drive NO GO Saliency Drive GO Memory Memory Because Addiction Changes Brain Circuits Adapted from Volkow et al., Neuropharmacology, 2004.

The Memory of Drugs Front of Brain Amygdala not lit up Amygdala activated Back of Brain Nature Video Cocaine Video Photo courtesy of Anna Rose Childress, Ph.D.

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 Need to Treat the Whole Person! Pharmacological Treatments (Medications) Behavioral Therapies 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 Opiate agonists stabilize brain function in heroin addicts CB1 KO mice have decreased responses to multiple drugs of abuse Agonist Therapy Methadone Buprenorphine CB1 Antagonists Smokers who are poor nicotine metabolizers smoke less Inhibitors of metabolizing enzymes Stress triggers relapse in animal models of addiction and CRF antagonists interfere with the response to stress CRF Antagonists

But, drug addiction is a chronic illness with relapse rates similar to those of hypertension, diabetes, and asthma. McLellan et al., JAMA, 2000.

Percent of Patients Who Relapse 40 to 60% 30 to 50% 50 to 70% 50 to 70% Relapse Rates Are Similar for Drug Addiction & Other Chronic Illnesses 100 90 80 70 60 50 40 30 20 10 0 Drug Addiction Type I Diabetes Hypertension Asthma 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 Therefore

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 with prolonged abstinence from methamphetamine Normal Control Methamphetamine Abuser (1 month abstinent) high low Volkow et al., J. Neuroscience, 2001. Methamphetamine Abuser (14 months abstinent)

Percentage of Participants 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