40,000 30,000 20,000 10,000. Slide courtesy of Dr. Scott Hadland Source: National Center for Health Statistics, CDC Wonder

Transcription

1 The Teen Brain What s Going on in There? Sion Kim Harris, PhD Boston Children s Hospital Harvard Medical School Center for Adolescent Substance Abuse Research Sion.harris@childrens.harvard.edu Leading Causes of Death, Ages 15-24, United States, 2014 Motor Vehicle Crashes 24% Other Unintentional Injuries (3 out of 4 by poisoning ) 17% Homicides 18% Suicides 14% Leading Causes of Death, Ages 15-24, United States, 2014 Motor Vehicle Crashes 24% Other Unintentional Injuries 17% Alcohol and drugs are major (3 out of 4 by poisoning ) contributors to all of these Homicides 18% Suicides 14% TOTAL 73% Source: Heron M. Deaths: Leading causes for National vital statistics reports; vol 65 no 5. Hyattsville, MD: National Center for Health Statistics Source: Heron M. Deaths: Leading causes for National vital statistics reports; vol 65 no 5. Hyattsville, MD: National Center for Health Statistics A Public Health Crisis National Overdose Deaths (All Drugs) 60, Total deaths highest Female on record Male 137% increase since ,000 In MA, up 35% in one year ( ) 40,000 30,000 20,000 10,000 0 Slide courtesy of Dr. Scott Hadland Source: National Center for Health Statistics, CDC Wonder

2 The Age of the Brain Any Questions? 10 The human brain weighs about the same as a. A. Donut B. Six-pack of soda C. Chihuahua

3 Until the 1990 s, brain development was thought to be complete by about age 12 Teen Brain Adult Brain What we now know Adolescence is a critical period in brain development. The brain is still developing until about mid-20 s!! 13 Source: Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF 3rd, Herman DH, Clasen LS, Toga AW, Rapoport JL, 14 Thompson PM. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A May Slide courtesy of Ken Winters, PhD. 25;101(21): Available at: Definition: Critical Period Window in brain development when a part of the brain develops rapidly is highly sensitive to being shaped by environmental exposures and experiences Key Brain Development Processes until Mid-20s Pruning Myelination Source: Lubman DI, Cheetham A, Yücel M. Cannabis and adolescent brain development. Pharmacol Ther 2015;148: Brain cells (Neurons) 18

4 Construction Ahead Around age 12, brain cell connections start to undergo pruning based on use it or lose it (connections that are not used are pruned away) Source: Giedd J., et al., Neuropsychopharmacology Reviews (2015) 40, Available at: Construction Ahead The Brain s Information Superhighway: Myelinated axons = White Matter Tracts At the same time, myelin starts to form on brain cells and thicken, changing gray matter to white matter Myelin acts like insulation on an electrical wire - helps brain signals travel 100 times faster Source: Dr. Gordon J. Harris, MGH, White matter development from age 5 to 20 The Brain s Connectome: Adolescence/Young Adulthood is a Sensitive Period for Brain Wiring!! Neuropsychopharmacology Reviews advance online publication 22 October doi: /npp Image source: Dr. Van J. Wedeen, MGH, Source: Stevens MC, Skudlarski P, Pearlson GD, et al. Age-related cognitive gains are mediated by the effects of white matter development on brain network integration. Neuroimage 2009;48:

5 Result when pruning and myelination are complete: faster, but fewer, connections in the brain Source: Baker STE, Lubman DI, Yücel M, et al. Developmental Changes in Brain Network Hub Connectivity in Late Adolescence. Journal of Neuroscience 2015;35: Available at: To go from this To being able to do this Diekhof EK, Gruber O. When desire collides with reason: functional interactions between anteroventral prefrontal cortex and nucleus accumbens underlie the human ability to resist impulsive desires. The Journal of Neuroscience. 2010;30(4): The teen brain is highly neuroplastic It s a double-edged sword Adolescence is a great time for getting good at something! Opportunity Vulnerability Renard J, Vitalis T, Rame M, Krebs MO, Lenkei Z, Le Pen G, Jay TM. Chronic cannabinoid exposure during adolescence leads to longterm structural and functional changes in the prefrontal cortex. Eur Neuropsychopharmacol Jan;26(1):

6 % with Alcohol Disorder The adolescent/young adult brain is more vulnerable than adult brain to the effects of alcohol and drugs This is Your (Developing) Brain on Drugs 32 Age at First Drink and Risk of Alcohol Addiction Age at First Use and Risk of Marijuana Addiction Age at First Drink Source: Hingson RW, Heeren T, Winter MR. Age at drinking onset and alcohol dependence. Arch Pediatr Adolesc Med. 2006;160: Source: Substance Abuse and Mental Health Services Administration. (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA Findings). Rockville, MD. Why are adolescents more vulnerable to developing an addiction to substances? Reason 1: Teen brains are affected by alcohol and drugs differently from adult brains Let s look at the science regarding alcohol Slide courtesy of Ken Winters, PhD. 36

7 Animal Studies Adolescent rats were found to be less sensitive than adult rats to alcohol and drug effects in terms of Sedation (sleepiness) Motor impairment Drunk Adult Drunk Adolescent Slide courtesy of Ken Winters, PhD. Sources: White AM, Truesdale M, Bae J, et al. Differential effects of alcohol on motor coordination in adolescent and adult rats. Pharmacology Biochemistry and Behavior. 2002;73: Silveri MM, Spear LP. Decreased sensitivity to the hypnotic effects 37 of ethanol early in ontogeny. Alcoholism: Clinical and Experimental Research. 1998;22: Slide courtesy of John R Knight, MD. Wide-Awake Drunk Teens Reason 2: Teen brains respond differently to rewarding things than adults Front Brain areas with greatest changes during adolescence Back Source: Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience. 1999;2: Used with permission. Source: Boston Globe August 21, 2003 Slide courtesy of John R Knight, MD. The Reward Pathway marijuana Source: NIDA Ventral-Tegmental Area Source: NIDA

8 Comparing Reward Pathway Function across Age Groups MRI study showed adolescent brains showed a much stronger response to large rewards than children or adults Teen brains respond more strongly to highly stimulating activities, like Source: Galvan A et al. Journal of Neuroscience, 2006,26(25): Reason 3: The gas pedal develops faster than the braking system The Hot vs. Cool Head Front Brain areas with greatest changes during adolescence Back (Reward pathway) Source: Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience. 1999;2: Used with permission. Adult Source: Source: Casey Casey BJ, BJ, Getz S, al., Galvan Development A. The adolescent Reviews. 2008; brain. 28(1): Dev Rev ;28(1): Used with permission.

9 The Developing Brain: Key Points Teen brains have higher physical tolerance and stronger reward response to addictive substances (so tend to binge when using) Teen brains change faster in response to using alcohol/drugs, and therefore can get addicted faster Parents need to help be the teen s prefrontal cortex Alcohol and Drug Effects on Teen Memory and Thinking 50 Hippocampus: The Key to the SAT s Binge drinking reduces growth of new brain cells and dendrites in the hippocampus 51 Source: He et al. European Journal of Neuroscience 2005; 21(10): Source: cations/arh314/ htm 52 Hippocampal Size and Teen Drinking Hippocampus 10-35% smaller among heavydrinking teens Marijuana and Memory THC in marijuana suppresses activity of hippocampal cells below the level needed to trigger memory formation With chronic THC exposure, brain cell connections involved in memory are gradually lost due to continual suppression Slide courtesy of Susan Tapert, PhD. Nagel BJ, Schweinsburg AD, Phan V, Tapert SF. Reduced hippocampal volume among adolescents with alcohol use disorders without psychiatric comorbidity. Psychiatry Research Neuroimaging. 2005;139: Source: Ranganathan M, D Souza DC. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berl) 2006;188:425 44; Broyd SJ, van Hell HH, Beale C, et al. Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. Biol Psychiatry 2016;79:

10 Average IQ Marijuana and Hippocampal Volume Adult heavy marijuana users who started in adolescence had an avg % smaller hippocampal volumes compared to non-users Marijuana users Non-users Teen Marijuana Use and Change in IQ Sources: Yücel M, Solowij N, Respondek C, Whittle S, Fornito A, Pantelis C, Lubman DI. Regional brain abnormalities associated with long-term heavy cannabis use. Arch Gen Psychiatry Jun;65(6): Rubino T, Realini N, Braida D, et al. Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus. 2009;19: IQ and Marijuana Use The Dunedin Study (N=1,037) Change in IQ from 13 to 38 yrs old 13 yrs old 38 yrs old yrs (Pre-initiation) 18 yrs 21 yrs 32 yrs 38 yrs Assessment ages Source: Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RS, McDonald K, Ward A, Poulton R, Moffitt TE. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A Oct 2;109(40):E Available at: Never used marijuana Regular marijuana 3+ years Dose-related IQ change Regular mj use - 3+ yrs National Academies of Sciences Report on Marijuana, Jan Regular mj use - 2 yrs Regular mj use - 1 yr Used infrequently Never used Available at:

11 Strong evidence for link between marijuana and psychotic disorders Many longitudinal studies have found increased psychosis or schizophrenia risk with more frequent marijuana use during youth 15-year follow-up of 45,570 Swedish year-olds Source: Andreasson S, et al., Lancet, 1987 Copyright 2013 John R Knight MD, Center for Adolescent Substance Abuse Research (CeASAR), Boston Children s Hospital. All rights reserved. Genetic Risk: Marijuana Use and Schizophrenia by Age 26 Brain Development is shaped by genes & experiences at critical points in time 63 Source: Caspi et al. Biol Psychiatry Many studies show white matter differences between young adult regular marijuana users who started in adolescence vs. non-users Recent longitudinal brain imaging studies provide confirmation: Becker et al., 2015 Non-user Daily user Source: Arnone D, Barrick TR, Chengappa S et al. Corpus callosum damage in heavy marijuana use: Preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. NeuroImage, 2008; 41: Camchong J et al., Cerebral Cortex, 2016

12 Avg. % THC Content among Confiscated Cannabis Products in U.S. ( ) Marijuana is a very different substance today than it was 20 years ago, bringing greater risks 14% 12% 10% 8% 6% 4% 2% 0% Marijuana for sale in Colorado averages 17% to 18% THC ~4% ~12% *Source: ElSohly et al., Biological Psychiatry, *38,681 samples Avg. % THC Content among Confiscated Cannabis Products in U.S. ( ) Highly potent marijuana edibles 14% 12% 10% 8% 6% 4% 2% 0% Marijuana for sale in Colorado averages 17% to 18% THC ~4% % Cannabidiol (antipsychotic) ~12% *Source: ElSohly et al., Biological Psychiatry, *38,681 samples 23-year-old Luke Goodman on ski vacation in Colorado with family shot himself with his own gun Forms of Butane Hash Oil contains up to 90% THC! Shatter Dabs Budder Earwax Vaping

13 As THC content increases, we see more adverse effects: Change in ED Visit Rate Caused by Marijuana Only (no other substance involved), by Age Group Paranoia Anxiety and panic Hallucinations Erratic mood swings Aggressive behavior Emergency Department Visits Caused by Marijuana Use (Rate per 100,000 people) Emergency Department Visits Caused by Marijuana Only (Rate per 100,000 people) Source: National Drug Abuse Warning Network, 2011 Source: Zhu H, Wu LT. Trends and Correlates of Cannabis-involved Emergency Department Visits: 2004 to J Addict Med Nov/Dec;10(6): % 60% 50% 40% 30% 20% 10% 14% Among adolescents, marijuana accounts for more treatment admissions than all other substances combined 10% 1% 5% 64% 0% Alcohol Heroin/Opiates Cocaine Meth/Other Marijuana Stimulants Source: SAMHSA National Treatment Episode Data Set, Table 2.1a Marijuana Withdrawal Symptoms Restlessness, anxiety Increased irritability, anger, aggression Difficulty falling and staying asleep, nightmares/strange dreams Boredom Decreased appetite Source: Milin R, Manion I, Dare G, Walker S. Prospective assessment of cannabis withdrawal in adolescents with cannabis dependence: a pilot study. J Am Acad Child Adolesc Psychiatry Feb;47(2): The Next Big Tobacco Slide courtesy of Kevin Sabet, PhD/ 77 Slide courtesy of Edventi.com

14 Medicalization to Sell Tobacco Marketing tobacco to youth Marketing Marijuana to Youth Advise DELAYING until age 21+ The future promise of any nation can be directly measured by the present prospects of its youth - John F. Kennedy

15