The Science of Addiction: The Brain on Adolescence Ken Winters, Ph.D. Senior Scientist, Oregon Research Institute & Adjunct Faculty, Dept. of Psychology, University of Minnesota winte001@umn.edu December 14, 2016
1. Addiction as brain disease 4. Summary 2. Brain development 3. Developing brain & drug risk
Other Resources Dahl, R.E. & Spear, L.P. (Eds.) (2004). Adolescent brain development: vulnerabilities and opportunities. NY, NY: Annals of the New York Academy of Sciences, Volume 1021. Drugfree.org http://www.drugfree.org/why-do-teens-act-thisway/adolescent-brain-development/ National Institute on Drug Abuse: Drugs, Brains, and Behavior: The Science of Addiction https://www.drugabuse.gov/publications/drugs-brainsbehavior-science-addiction/drugs-brain Volkow, N., et al., (2014). Adverse health effects of marijuana use. The New England Journal of Medicine, 370, 2219-2227.
1. Addiction as brain disease
nucleus accumbens VTA/SN Drugs of abuse increase dopamine in the nucleus accumbens AMPHETAMINE % of Basal Release frontal cortex % of Basal Release The Reward Circuit 1100 1000 900 800 700 600 500 400 300 200 100 0 150 0 1 2 3 4 5 hr MARIJUANA 125 100 0 20 40 60 Tanda, et al, Science 1997. 80
Dopamine D2 Receptors are Lower in Addiction Cocaine DA DA DA DA DA DA DA DA DA DA DA DA Meth Reward Circuits Non-Drug Abuser Alcohol DA DA DA DA DA DA Heroin control addicted Reward Circuits Drug Abuser
What about recovery?
Your Brain After Cocaine Normal Cocaine Addict - 10 days drug free Cocaine Addict - 100 days drug free Yellow = normal brain functioning
1. Brain imaging: addiction as brain disease 2. Brain development
Cautions Brain imaging studies of development are based on small samples gender, ethnic and cultural differences may be significant. The role of hormones and early experiences on brain development are likely significant
Major Ongoing Projects on Brain Development The Baby Connectome Project (as part of the larger Human Connectome Project) ~1000 subjects from 5 to 21 years old
Major Ongoing Projects on Brain Development Adolescent Brain Cognitive Development National Longitudinal Study Ten year longitudinal study of 10,000 children from age 10 to 20 years to assess effects of drugs on individual brain development trajectories
Adolescence is a period of profound brain maturation. We thought brain development was complete by adolescence
Brain Weight by Age I m adult-size now! Males Females Newborn Age Source: Dekaban, A.S. and Sadowsky, D. Annals of Neurology, 4:345-356, 1978 16
We now know maturation is not complete until about age 25.
Who first figured out when the teen brain is mature? Neuroscientists, using brain imaging technology Division of Motor Vehicles Board of Elections State Liquor Control Board State Tobacco Control Board Actuaries at Car Rental Companies
An Immature Brain = Less Brakes on the Go System
Maturation Occurs from Back to Front of the Brain and Inside to Outside Images of Brain Development in Healthy Youth (Ages 5 20) Earlier: Limbic Motor Coordination Emotion Motivation Later: Prefrontal Judgment Blue represents maturing of brain areas Source: PHAS USA 2004 May 25; 101(21): 8174-8179. Epub 2004 May 17.
Imbalanced Neurodevelopment
Seven Implications of Brain Development for Adolescent Behavior Preference for 1. physical activity 2. high excitement and rewarding activities 3. activities with peers that trigger high intensity/arousal 4. novelty Less than optimal 5. control of emotional arousal 6. consideration of negative consequences Greater tendency to 7. be attentive to social information 8. take risks and show impulsiveness
Risk-Taking Based on science of brain development, a modern view of risk taking in adolescence is normative; important to development evolutionarily adaptive due primarily to emotional and contextual, not cognitive, factors
Impact of Peer Presence on Risky Driving in Simulated Context peer effect Chein et al., in press
An Immature Brain = Low Brain Power Source: US News & World Report, 2005
A Developing Brain > Impact from Environment? Source: US News & World Report, 2005 Since Hebb (1949) first postulated that the strengthening of synaptic elements occurs through functional validation, researchers have applied this approach to understanding the sculpting of the immature brain. In this manner, the brain becomes wired to match the needs of the environment. Extensions of this hypothesis posit that exposure to both positive and negative elements before adolescence can imprint on the final adult topography in a manner that differs from exposure to the same elements after adolescence. (Anderson, 2003, Neuroscience & Biobehavioral Reviews)
1. Brain imaging: addiction as brain disease 2. Brain imaging: brain development 3. Developing brain & drug risk
Implications of Brain Development for Drug Abuse Vulnerability Are adolescents more susceptible than adults to drugs? 4 lines of evidence (acknowledgement to Linda Spear, Ph.D.) Unethical to give human adolescents drugs in the laboratory; much of the best evidence comes from indirect evidence and adolescent rat studies.
Implications of Brain Development for Drug Abuse Vulnerability Data on Alcohol Are adolescents more susceptible than adults to drugs? 4 lines of evidence (acknowledgement to Linda Spear, Ph.D.) Unethical to give human adolescents alcohol in the laboratory; much of the best evidence comes from adolescent rat studies.
Evidence from epidemiological studies Drug use starts early and peaks in the teen years
Percentages of Past Year Alcohol Use Disorder (Abuse or Dependence) Among Adults Aged 21 or Older, by Age of First Use (SAMHSA, 2005) 20 15 16 15 Fewer Problems in Those Who Start Later % 10 9 5 4.2 2.6 0 <12 yrs 12-14 yrs 15-17 yrs 18-20 yrs 21+ yrs Age Started Drinking
Percentages of past year alcohol use disorder among those with a recent onset (prior 2 years; n = 4074) of alcohol use (Winters & Lee, 2007) 20 15 Lower Rates with Older Recent Users % 10 5 7.2 8.2 9.2 8.3 9.5 9.2 9.9 6.7 4.1 5.9 3.7 0 * * * * 12 y 13 y 14 y 15 y 16 y 17 y 18 y 19 y 20 y 21 y 22-26 y * p <=.05; compared to 22-26y group Age of Person in Years
Are adolescents more susceptible to alcohol than adults? Adolescent rats are less sensitive to the sedative and motor impairment effects of intoxication. Adolescent rats are more sensitive to the social disinhibition effects of alcohol. #2 and #3 : May contribute to binge drinking and increased risk to alcohol dependence.
The Water Maze Test Hidden Slide courtesy Sion Kim Harris, Ph.D. Saline vs alcohol Measures -Swimming speed -Time to find platform
Wanna look for some cheese with me? Sure!
Implications of Brain Development for Drug Abuse Vulnerability Data on Are adolescents more susceptible than adults to drugs? Marijuana 4 lines of evidence (acknowledgement to Linda Spear, Ph.D.) Unethical to give human adolescents alcohol in the laboratory; much of the best evidence comes from adolescent rat studies.
Percentages of Adult Cannabis Dependence as Function of Age of Onset of Use (National Household Survey on Drug Abuse, 2000-2001) 10 8 Fewer Problems in Those Who Start Later % 6 4 5.4 6 4.4 2 0 1.9 0.5 11-13 yrs 14-15 yrs 16-17 yrs 18-20 yrs 21+ yrs Age of Cannabis Onset
Percentages of past year cannabis use disorder among those with a recent onset (prior 2 Years; n = 2176) of cannabis use (Winters & Lee, 2007) % 20 15 10 5 6 17.4 14.1 16.4 15.4 10.6 Lower Rates with Older Recent Users 12.8 8 6.9 4.4 3 0 * * * * * * * 12 y 13 y 14 y 15 y 16 y 17 y 18 y 19 y 20 y 21 y 22-26 y * p <=.05; compared to 22-26y group Age of Person in Years
Marijuana and Cognitive Development 0.4 Adolescent Vulnerability 1 Diagnosis 2 Diagnoses 3 Diagnoses Change in Full Scale IQ (in standard deviation units) 0.2 0 0.2 0.4 0.6 0.8 p=.44 p=.09 p=.02 Cannabis Dependent Before Age 18 (n=17) Not Cannabis Dependent Before Age 18 (n=57) Cannabis Dependent Before Age 18 (n=12) Not Cannabis Dependent Before Age 18 (n=21) Cannabis Dependent Before Age 18 (n=23) Source: Meier MH et al., PNAS Early Edition 2012. Not Cannabis Dependent Before Age 18 (n=14)
CA MN Source: Jackson, et al. (2016). Proceedings of the National Academy of Sciences, 113(5), E500-E508.
However, the cotwin control analysis revealed a different pattern of results. This analysis holds constant the potentially confounding influences of genetics and shared environment. Twin pairs that were discordant for marijuana use did not reveal significant differences in IQ change between MZ or DZ siblings, suggesting that familial confounds were responsible for the association between adolescent marijuana use and CA decline in IQ scores (Jackson et al., 2016). MN Source: Jackson, et al. (2016). Proceedings of the National Academy of Sciences, 113(5), E500-E508.
More about Marijuana Are adolescents more susceptible than adults to drugs? 4 lines of evidence (acknowledgement to Linda Spear, Ph.D.) Unethical to give human adolescents alcohol in the laboratory; much of the best evidence comes from adolescent rat studies.
Support for Marijuana Legalization in the United States Has Reached Unprecedented Levels Sources: Gallup http://bit.ly/olrseq and GSS
Marijuana and Legalization, Nov., 2016 Total # of states: 29 and D.C. Recreational use: 8 states and D.C Medical use only: 21 Decriminalized only: 5
Source: Mehmedic et al., 2010 14 Average THC and Cannabidiol (CBD) Levels in the US: 1960-2011 MARIJUANA POTENCY 12 10 8 6 THC: Psychoactive Ingredient CBD: Non Psychoactive (Medicinal) Ingredient 4 2 0 196 0 196 5 197 0 197 4 197 8 198 0 198 3 198 4 198 5 198 6 199 0 199 2 199 3 199 5 199 6 THC 0.2 0.24 0.39 0.47 1 1 1.5 3.3 3.3 3.5 3.5 3.1 3.1 4 4.54 5.16 4.96 4.67 5.4 6.18 7.26 7.18 8.33 8.09 9.08 10.3 10.3 9.91 11 11.4 CBD 0.28 0.31 0.38 0.36 0.33 0.31 0.42 0.4 0.41 0.43 0.45 0.47 0.42 0.46 0.46 0.46 0.53 0.48 0.41 199 7 199 8 199 9 200 0 200 1 200 2 200 3 200 4 200 5 200 6 200 7 200 8 200 9 201 0 201 1
Miller s Review of the Marijuana and Mental Health Connection Disorder Cross-Sectional Data Longitudinal Data Schizophrenia ++ ++ Bipolar + Anxiety Disorders + + Depressive Disorders + + Risk of Suicide + Key: ++ = several studies; +a few studies Yellow box = risk greater when MJ use onset during youth. Miller, C. L. (in press). The impact of marijuana on mental health. In K. Sabet & K.C. Winters, Contemporary health issues on marijuana. NY: Oxford Press.
Miller s Review of the MJ and Mental Health Connection The preponderance of evidence reviewed in this chapter substantiates not only a significant, causal role for marijuana in chronic psychotic syndromes but also a strong association with mood disorders and suicidal ideation.
Implications of Brain Development for Drug Abuse Vulnerability Are adolescents more susceptible than adults to drugs?
1. Could there be inherent risk factors of brain development that contribute to drug use? Preference for. 1. physical activity 2. high excitement and rewarding activities 3. activities with peers that trigger high intensity/arousal 4. novelty Less than optimal.. 5. control of emotional arousal 6. consideration of negative conseq. Greater tendency to 7. be attentive to social information 8. take risks and show impulsiveness
2. Adolescents, as adults, have pleasure centers in the brain.
3. The adolescent pleasure brain center may be more vulnerable to the effects of drugs compared to adolescents (Chambers, Taylor and Potenza, 2003) Evidence that dopamine activity is more robust during adolescence. If dopamine production is more pronounced during adolescence, risk of drug abuse could be heightened > sensitivity to initial drug effects > motivation to continue use > difficulty to reduce use
4. Does early use sensitize the brain? Early exposure may recalibrate the brain s sensitivity to the drug of abuse and to other drugs.
1. Brain imaging: addiction as brain disease 4. Summary 2. Brain imaging: brain development 3. Developing brain & drug risk
Summary Adolescence is an extended period of transition from reliance on adults to independence Normal adolescence is characterized by. increase in conflicts with family members desire to be with one s friends resistance to messages from authority irritability risk taking proclamations of sheer boredom
Summary The brain undergoes a considerable amount of development during the teen years. The last area to develop is the prefrontal cortex, which is involved in planning, decision making and impulse control.
Summary Several lines of evidence suggesting that adolescents are more vulnerable to the effects of drugs particularly alcohol than adults.
Brain Development: Reinforcing Need for Prevention and Treatment Youth is a particularly vulnerable period for developing a substance use disorder. Prevention and treatment programs are vital.
Brain Development: Opportunities for Prevention and Treatment Discuss with teenagers the science of the neurobiology of addiction
Brain Development: Opportunities for Prevention and Treatment Discuss the implications of using substances when the brain is still developing.
Human Data: Drug s Effects on Memory
Brain Development: Implications for Prevention and Treatment Teach important skills not optimal for the teen brain impulse control second thought processes social decision making dealing with risk situations taking healthy risks
Classroom Resources There are now some age-appropriate resources to educate youth about their developing brain. Resource from BSCS Drug Abuse, Addiction and the Adolescent Brain (www.bscs.org) Hazelden has published an 8-lesson multi media resource: Drugs and the Developing Brain (www.hazelden.org)
Parent Resources
Prevent_Intervene_Get Treatment_Recover www.drugfree.org
Working with Parents P = Promote activities that capitalize on the strengths of the developing brain. A = Assist children with challenges that require planning. R = Reinforce their seeking advice from adults; teach decision making. E = Encourage lifestyle that promotes good brain development. N = Never underestimate the effects of drugs on the developing brain; emphasize the importance of drug-free lifestyle. T = Tolerate the oops behaviors due to an immature brain.
For additional information and follow-up questions contact: Ken Winters, Ph.D. winte001@umn.edu THANK YOU Questions and Discussion Evaluation : SAMHSA s GPRA