1 Wilson M. Compton, MD, MPE Deputy Director, National Institute on Drug Abuse Tobacco Research at NIDA: Neuroscience, Treatment and Regulatory-related studies • 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) Themes for NIDA Research All Drugs Abused by Humans Raise Brain Dopamine Levels in the Nucleus Accumbens Nestler, Nature Neurosci, 2005 ` Time After Methamphetamine Dopamine (nM) METHAMPHETAMINE 2000 1500 1000 500 0 5 1 2.5 Dose (mg/kg IV) 0 20 40 60 80min 0 100 150 200 250 0 1 2 3 hr Time After Nicotine % of Basal Release NICOTINE Di Chiara et al.
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Neuroscience, Treatment and Regulatory-related studiesWilson M. Compton, MD, MPE Deputy Director, National Institute on Drug Abuse Tobacco Research at NIDA: Neuroscience, Treatment
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Wilson M. Compton, MD, MPE Deputy Director, National Institute on Drug Abuse
Tobacco Research at NIDA:
Neuroscience, Treatment and
Regulatory-related studies
• 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)
Themes for NIDA Research
All Drugs Abused by Humans Raise Brain Dopamine Levels in the Nucleus Accumbens
Nestler, Nature Neurosci, 2005
`
Time After Methamphetamine
Do
pam
ine
(nM
)
METHAMPHETAMINE 2000
1500
1000
500
0
5
1 2.5
Dose (mg/kg IV)
0 20 40 60 80min
0
100
150
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250
0 1 2 3 hr
Time After Nicotine
% o
f B
asal
Rel
ease
NICOTINE
Di Chiara et al.
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Kimura et al., Nature Neuroscience 2007.
Habenula neurons increased firing for NO REWARD and decreased firing for REWARD Dopamine neurons increased firing for REWARD and decreased firing for NO REWARD.
*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.
In the USA 44% Cigarettes Consumed by
the Mentally Ill Lasser et al., JAMA 2011
People with Severe Mental Illness Much More Likely to Use Tobacco and Other Drugs
• 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
*Hartz SM, et al., JAMA Psychiatry, 7: 248-54, 2014
>4 Drinks Alcohol/Day Daily Smoking > 1 mo
Marijuana > 21x/year Other Drugs > 10x
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.
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Use of Mentholated Cigarette May Play Role in Cocaine Dependence and Abstinence
*Winhusen TM et al., Drug and Alcohol Dependence 133: 845-51, 2013
• 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
*Winhusen TM et al., J Clin Psychiatry 75: 336-43, 2014
Stimulant Abstinence as a function of stimulant-dependent diagnosis and cigarette type
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
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
Monitoring the Future Study, University of Michigan
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8th Grade 10th Grade 12th Grade
Tobacco Cigarettes
E-Cigarettes
Past Month Use of E-Cigs vs. Traditional Cigarettes in the 2014 Monitoring the Future Study of 8th, 10th and 12th Grade Students in USA
8.1%
16.2% 17.1%
4.0%
7.2%
13.6%
Large Numbers of Youth in USA Using E-Cigarettes Without Prior Use of Tobacco
Monitoring the Future Study, University of Michigan
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2
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8th Grade 10th Grade 12th Grade
E-Cigs Only
E-Cigs and Any LifetimeTobacco
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 8th, 10th and 12th Grade Students in USA
36%
30%
21%
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Adolescent Brain Cognitive Development National Longitudinal Study
Youth Past 12 Month Alcohol, Blunt, and Marijuana Use Prevalence* By Past 30 Day Tobacco Use
* 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.
WARNING: Interim preliminary results from a portion of the baseline wave. Results from entire
baseline wave will differ. Inferences from these data should be made with caution.
Source: Society for Research on Nicotine and Tobacco Annual Meeting, February 2015
*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).
The PATH Study Baseline (interim analysis)
Youth Past 12 Month Internalizing Severity* By Past 30 Day Tobacco Use
WARNING: Interim preliminary results from a portion of the baseline wave. Results from entire
baseline wave will differ. Inferences from these data should be made with caution.
Source: Society for Research on Nicotine and Tobacco Annual Meeting, February 2015
*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).
The PATH Study Baseline (interim analysis)
Youth Past 12 Month Externalizing Severity* By Past 30 Day Tobacco Use
WARNING: Interim preliminary results from a portion of the baseline wave. Results from entire
baseline wave will differ. Inferences from these data should be made with caution.
Source: Society for Research on Nicotine and Tobacco Annual Meeting, February 2015
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0%
20%
40%
60%
80%
100%Alcohol Use Past 12 Months (n=10050) Blunt Use Past 12 Months (n=1770) Any Marijuana Use Past 12 Months (n=3002)
* 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.
The PATH Study Baseline (interim analysis)
Adult Past 12 Month Alcohol, Blunt, and Marijuana Use Prevalence* By Current Tobacco Use*
WARNING: Interim preliminary results from a portion of the baseline wave. Results from entire
baseline wave will differ. Inferences from these data should be made with caution.
Source: Society for Research on Nicotine and Tobacco Annual Meeting, February 2015
0%
20%
40%
60%
80% Low (n=8486) Moderate (n=3405) High (n=2452)
The PATH Study Baseline (interim analysis)
Adult Past 12 Month Internalizing Severity By Current Tobacco Use
WARNING: Interim preliminary results from a portion of the baseline wave. Results from entire
baseline wave will differ. Inferences from these data should be made with caution.
Source: Society for Research on Nicotine and Tobacco Annual Meeting, February 2015
0%
20%
40%
60%
80%
Low (n=10407) Moderate (N=3458) High (n=410)
The PATH Study Baseline (interim analysis)
Adult Past 12 Month Externalizing Severity By Current Tobacco Use
WARNING: Interim preliminary results from a portion of the baseline wave. Results from entire
baseline wave will differ. Inferences from these data should be made with caution.
Source: Society for Research on Nicotine and Tobacco Annual Meeting, February 2015
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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
• 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)