Wilson compton nida

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 IntegratedTreatments
• Vulnerable Populations (e.g., pregnant women, mental illness)
• IntegratedTobacco 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
%ofBasalRelease
NICOTINE
Di Chiara et al.

2
Kimura et al., Nature Neuroscience 2007.
Habenula neurons increased firing for NO
REWARDand decreased firing for REWARD
Dopamine neurons increased firing for REWARD
and decreased firing for NO REWARD.
HABENULA
Habenula inhibits dopamine neurons
Habenula communicatesnegative
reward signals to dopamine neurons
Habenula and Negative Reward
Biological Psychiatry
Convergent Results Support CHRNA5/A3/B4
Gene Cluster Association with Nicotine Dependence
Medial
habenula
a5, a3, 4, have a high concentration in
habenula and interpeduncular nucleus
Genes Affect Risk for Smoking Progression,
Odds of Quitting and Whether Medications
May Help
*Chen LS et al.,Am J Psychiatry 169: 735-42, 2012*Belsky DW, et al., JAMA Psychiatry 70: 534-42, 2013 *Chen LS et al.,Addiction 109: 128-37, 2013

3
Mental
Disorder
Addictive
Disorder
Comorbid
Disorders
COMORBIDITY
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)****
Smoking Rates
*2010 National Survey on Drug Use and Health, SAMHSA 2011. **Lasser et al.,JAMA 2000; 284(20): 2606-2610.
***Ziedonis et al., Nic andTob 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 UseTobacco 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 PersonsAged
12 or Older, by PastYear Substance UseTreatment: 2005 to 2009
The NSDUH Report: Nicotine Dependence among Persons Who Received Substance UseTreatment, SAMHSA 2011.

4
Use of Mentholated Cigarette May Play Role in
Cocaine Dependence and Abstinence
*WinhusenTM et al., Drug andAlcohol Dependence 133: 845-51, 2013
• Smoking cessationtreatmentcan improve quit
rates in individuals also undergoing concurrent
treatmentfor stimulant addiction,
• However,use of menthol cigarettesmay complicate
cocaine treatmentoutcomesfor cocaine-dependent
individuals
*WinhusenTM 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., MaintenanceTreatment withVareniclineforSmokingCessation in PatientswithSCZ and BipolarDisorder, 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 DependenceTreatmentin
Inpatient Psychiatry:A Randomized Controlled Trial, American Journal of Public
Health, 104: 1557-65, 2014

5
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 ofThomas Eissenberg,Virginia Commenwealth University,USA
MoreYouth in USA Using E-CigarettesThanTobaccoCigs
Monitoring the Future Study,University of Michigan
0
2
4
6
8
10
12
14
16
18
8th Grade 10th Grade 12th Grade
Tobacco Cigarettes
E-Cigarettes
Past MonthUse of E-Cigs vs.TraditionalCigarettes in the 2014 Monitoring the
FutureStudy of 8th, 10th and 12th GradeStudents inUSA
8.1%
16.2%
17.1%
4.0%
7.2%
13.6%
Large Numbers ofYouth in USA Using E-Cigarettes
Without Prior Use ofTobacco
Monitoring the Future Study,University of Michigan
0
2
4
6
8
10
12
14
16
18
20
8th Grade 10th Grade 12th Grade
E-Cigs Only
E-Cigs and Any Lifetime
Tobacco
Past MonthUse of E-Cigarettes AmongYouth with/without Any LifetimeUse of
Tobacco Cigarettes orSmokelessTobacco in the 2014 Monitoring the Future Study
of 8th, 10th and 12th GradeStudents in USA
36%
30%
21%

6
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.
2011 2012 2013 2014 2015 2016
Contract Award1
Baseline
Field Test
Wave 2 Wave 3
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

7
0%
20%
40%
60%
80%
100%
Population Any Tobacco
Use
Cigarettes E-cigarettes Cigarillos Hookah Smokeless,
excl snus
Traditional
cigars
Filtered
cigars
Pipe Snus
Alcohol Use Past 12 Months (n=1023)
Blunt Use Past 12 Months (n=337)
Any Marijuana Use Past 12 Months (n=596)
Suppressed
Suppressed
Suppressed
Suppressed
The PATH Study Baseline (interim analysis)
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
0%
20%
40%
60%
80%
Population Any
Tobacco Use
Excl snus
Traditional
cigars
Filtered
cigars
Pipe Snus
Low (n=2852)
Moderate (n=1759)
High (n=1421)
Suppressed
Suppressed
Suppressed
Suppressed
*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 Internalizing Severity* By Past 30 Day Tobacco Use
0%
20%
40%
60%
80%
Population Any
Tobacco
Use
Excl snus
Traditional
cigars
Filtered
cigars
Pipe Snus
Low (n=2927)
Moderate (N=2492)
High (n=573)
Suppressed
Suppressed
Suppressed
Suppressed
*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).
Youth Past 12 Month Externalizing Severity* By Past 30 Day Tobacco Use

8
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.
Adult Past 12 Month Alcohol, Blunt, and Marijuana Use Prevalence* By
Current Tobacco Use*
0%
20%
40%
60%
80% Low (n=8486) Moderate (n=3405) High (n=2452)
Adult Past 12 Month Internalizing Severity By Current Tobacco Use
0%
20%
40%
60%
80%
Low (n=10407) Moderate (N=3458) High (n=410)
Adult Past 12 Month Externalizing Severity By Current Tobacco Use

9
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 IntegratedTreatments
• Vulnerable Populations (e.g., pregnant women, mental illness)
• IntegratedTobacco Epidemiology (MTF, PATH)
Themes for NIDA Research

Wilson compton nida

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