% of Basal Release Dopamine (nm) Wilson M. Compton, MD, MPE Deputy Director, National Institute on Drug Abuse Tobacco Research at NIDA: Neuroscience, Treatment and Regulatory-related studies Themes for NIDA Research Basic Research Genetics (understanding impact of genetics on vulnerability to smoking-related morbidity/mortality) Biomarkers of vulnerability Prevention Research (ABCD) Medications Development Behavioral and Integrated Treatments Vulnerable Populations (e.g., pregnant women, mental illness) Integrated Tobacco Epidemiology (MTF, PATH) All Drugs Abused by Humans Raise Brain Dopamine Levels in the Nucleus Accumbens ` 2000 1500 1000 METHAMPHETAMINE Dose (mg/kg IV) 5 2.5 1 500 0 0 20 40 60 80min Time After Methamphetamine 250 200 NICOTINE 150 100 0 0 1 2 3 hr Time After Nicotine Di Chiara et al. Nestler, Nature Neurosci, 2005 1
Habenula and Negative Reward HABENULA Habenula neurons increased firing for NO REWARD and decreased firing for REWARD Dopamine neurons increased firing for REWARD and decreased firing for NO REWARD. Kimura et al., Nature Neuroscience 2007. Habenula inhibits dopamine neurons Habenula communicates negative reward signals to dopamine neurons Convergent Results Support CHRNA5/A3/B4 Gene Cluster Association with Nicotine Dependence a5, a3, 4, have a high concentration in habenula and interpeduncular nucleus Biological Psychiatry Medial habenula Genes Affect Risk for Smoking Progression, Odds of Quitting and Whether Medications May Help *Belsky DW, et al., JAMA Psychiatry 70: 534-42, 2013 *Chen LS et al., Am J Psychiatry 169: 735-42, 2012 *Chen LS et al., Addiction 109: 128-37, 2013 2
Mental Disorder Comorbid Disorders Addictive Disorder COMORBIDITY In the USA 44% Cigarettes Consumed by the Mentally Ill Lasser et al., JAMA 2011 Smoking Rates Normal Population: 23%* Alcoholism: 56.1% (past mo.); 43.5% (lifetime)** Drug Addictions: 67.9% (past mo.); 49% (lifetime)** Schizophrenia: 70-85%*** Depression: 44.7% (past mo.); 36.6% (lifetime)** Anxiety: 54.6% (past mo.); 46% (lifetime)** PTSD: 44.6% (past mo.); 45.3% (lifetime)** ADHD: 41-42% (adults)**** 19-46% (adolescents)**** *2010 National Survey on Drug Use and Health, SAMHSA 2011. **Lasser et al.,jama 2000; 284(20): 2606-2610. ***Ziedonis et al., Nic and Tob Res 2008;10(12):1691-1715. ****McLernon et al., Ann NY AcadSci 2008;1141: 131-147. People with Severe Mental Illness Much More Likely to Use Tobacco and Other Drugs >4 Drinks Alcohol/Day Daily Smoking > 1 mo Individuals with SMI were 4X more likely to be heavy alcohol users and almost 4X more likely to be regular marijuana users Protective factors usually associated with lower rates of substance use did not carry over to this population Marijuana > 21x/year Other Drugs > 10x *Hartz SM, et al., JAMA Psychiatry, 7: 248-54, 2014 Past Month Cigarette Use and Nicotine Dependence among Persons Aged 12 or Older, by Past Year Substance Use Treatment: 2005 to 2009 The NSDUH Report: Nicotine Dependence among Persons Who Received Substance Use Treatment, SAMHSA 2011. 3
Use of Mentholated Cigarette May Play Role in Cocaine Dependence and Abstinence Smoking cessation treatment can improve quit rates in individuals also undergoing concurrent treatment for stimulant addiction, However, use of menthol cigarettes may complicate cocaine treatment outcomes for cocaine-dependent individuals Stimulant Abstinence as a function of stimulantdependent diagnosis and cigarette type *Winhusen TM et al., J Clin Psychiatry 75: 336-43, 2014 *Winhusen TM et al., Drug and Alcohol Dependence 133: 845-51, 2013 Maintenance pharmacotherapy+ CBT can help individuals with SMI stay smoke-free Maintenance pharmacotherapy with varenicline and cognitive behavioral therapy improved prolonged tobacco abstinence rates for individuals with serious mental illness after 1 year of treatment and at 6 months after treatment discontinuation *Evins et al., Maintenance Treatment with Varenicline for Smoking Cessation in Patients with SCZ and Bipolar Disorder, JAMA 311: 143-54, 2014 Smoking Cessation Treatment During Psychiatric Hospitalization Reduces Smoking Rates & Improves Mental Health *Prochaska, Hall, et al., Efficacy of Initiating Tobacco Dependence Treatment in Inpatient Psychiatry: A Randomized Controlled Trial, American Journal of Public Health, 104: 1557-65, 2014 4
Electronic Nicotine Delivery Systems: Promise or Peril? Promise: If governments, parliaments, regulation agencies, and experts are able to restrain their yearning to restrict access to e-cigarettes, these products are likely to represent a revolution in public health. Etter, 2013. Peril: Urged on by myopic health professionals who seem to have lost any population health focus they might have had, this may become one of the biggest blunders of modern public health. Chapman, 2013. Middle ground: [our responses to ECIGs] will provide the greatest public health benefit when they are proportional, based on evidence, and incorporate a rational appraisal of likely risks and benefits. Hajek et al., in press. Slide Courtesy of Thomas Eissenberg, Virginia Commenwealth University, USA More Youth in USA Using E-Cigarettes Than Tobacco Cigs Past Month Use of E-Cigs vs. Traditional Cigarettes in the 2014 Monitoring the Future Study of 8 th, 10 th and 12 th Grade Students in USA 18 17.1% 16.2% 16 14 13.6% 12 10 8.1% Tobacco Cigarettes 8 7.2% E-Cigarettes 6 4 4. 2 0 8th Grade 10th Grade 12th Grade Monitoring the Future Study, University of Michigan Large Numbers of Youth in USA Using E-Cigarettes Without Prior Use of Tobacco Past Month Use of E-Cigarettes Among Youth with/without Any Lifetime Use of Tobacco Cigarettes or Smokeless Tobacco in the 2014 Monitoring the Future Study of 8 th, 10 th and 12 th Grade Students in USA 20 18 16 14 12 10 8 6 4 2 0 36% 3 21% E-Cigs Only E-Cigs and Any Lifetime Tobacco 8th Grade 10th Grade 12th Grade Monitoring the Future Study, University of Michigan 5
Adolescent Brain Cognitive Development National Longitudinal Study NIDA, NIAAA, NCI, NICHD, NIMHD, ORWH, NIMH, NINDS, OBSSR Ten year longitudinal study of 10,000 children from age 10 to 20 years to assess effects of drugs on individual brain development trajectories Population Assessment of Tobacco and Health (PATH) Study National, longitudinal cohort study of 45,000+ users of tobacco products and those at risk for tobacco use ages 12 and older in the U.S. Funded by the Center for Tobacco Products, FDA. Results from this study will inform the impact of FDA regulatory authority over tobacco products, and help to inform future activities. Contract Award 1 Field Test Baseline Wave 2 Wave 3 2011 2012 2013 2014 2015 2016 Today PATH Study Domains (examples) Baseline Sample 45,971 total (32,320 age 18+, 13,651 age 12-17) Outcomes Tobacco Product Use including Dual Use, Switching, New Products Tobacco Use Behaviors including Initiation, Cessation/Quitting, Relapse Health Outcomes Mediators/Moderators Demographics Knowledge, Attitudes, Beliefs, and Risk Perceptions Tobacco Addiction Peer, Environmental, Contextual influences Mental Health/Substance Abuse Co-morbidities 6
Youth Past 12 Month Alcohol, Blunt, and Marijuana Use Prevalence* By Past 30 Day Tobacco Use 10 8 6 Alcohol Use Past 12 Months (n=1023) Blunt Use Past 12 Months (n=337) Any Marijuana Use Past 12 Months (n=596) 4 2 Population Any Tobacco Cigarettes E-cigarettes Cigarillos Hookah Smokeless, Traditional Use excl snus cigars Filtered cigars Pipe Snus * Current use for each tobacco product is use in the past 30 days. Past year alcohol use is defined as using any alcohol in the past 12 months. Blunt use is report of having smoked all or part of a cigar with marijuana in it in the past 12 months. Any Marijuana use is blunt use or report of having used marijuana, hash, THC, grass, pot or weed in the past 12 months. Youth Past 12 Month Internalizing Severity* By Past 30 Day Tobacco Use Low (n=2852) 8 6 Moderate (n=1759) High (n=1421) 4 2 Population Any Cigarettes E-cigarettes Cigarillos Hookah Smokeless, Traditional Tobacco Use Excl snus cigars Filtered cigars Pipe Snus *Includes significant problems during the past year with: feeling very trapped/sad/depressed; trouble sleeping; feeling nervous/anxious/tense/scared; being distressed/upset about the past. Severity indicates the report of 0-1 problems (Low), 2-3 (Moderate), or 4 (High). Youth Past 12 Month Externalizing Severity* By Past 30 Day Tobacco Use Low (n=2927) 8 Moderate (N=2492) 6 High (n=573) 4 2 Population Any Cigarettes E-cigarettes Cigarillos Hookah Smokeless, Traditional Filtered Pipe Snus Tobacco Excl snus cigars cigars Use *Include two or more occurrences in the past year of: hard time paying attention/following instructions; lied/ conned to get something; bullied/threatened people; started a physical fight. Severity indicates the report of 0-1 (Low), 2-3 (Moderate), 4-5 (High). 7
Adult Past 12 Month Alcohol, Blunt, and Marijuana Use Prevalence* By Current Tobacco Use* 10 Alcohol Use Past 12 Months (n=10050) Blunt Use Past 12 Months (n=1770) Any Marijuana Use Past 12 Months (n=3002) 8 6 4 2 * Current cigarette use is 100 lifetime and currently use everyday or some days; other tobacco products currently use everyday or some days. Past year alcohol = any in past 12 mos. Blunt = smoked all or part of a cigar with MJ in past 12 mos. Any Marijuana = blunt or MJ, hash, THC, grass, pot or weed in past 12 mos. Adult Past 12 Month Internalizing Severity By Current Tobacco Use 8 Low (n=8486) Moderate (n=3405) High (n=2452) 6 4 2 Adult Past 12 Month Externalizing Severity By Current Tobacco Use Low (n=10407) Moderate (N=3458) High (n=410) 8 6 4 2 8
PATH Next Steps Data collection ongoing Selected analysis ongoing Accelerated efforts to have the PATH Study be a resource to the scientific community while ensuring highest data quality More Information: PATHstudyinfo.nih.gov Themes for NIDA Research Basic Research Genetics (understanding impact of genetics on vulnerability to smoking-related morbidity/mortality) Biomarkers of vulnerability Prevention Research (ABCD) Medications Development Behavioral and Integrated Treatments Vulnerable Populations (e.g., pregnant women, mental illness) Integrated Tobacco Epidemiology (MTF, PATH) 9