Hippocampal Network Changes Following Mindfulness Training in Tobacco Vaping Adolescents
Phase: NA
Conditions: Vaping Teens, Healthy Volunteers
Sponsor: National Institute on Drug Abuse (NIDA)

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Abbreviated Title: Mindfulness and Teen Vaping
Version Date: 07/21/2025
NIH IRB#: IRB001855
Abbreviated Title: Mindfulness and Teen Vaping
NIH IRB #: IRB001855
Version Date: 07/21/2025
Title: Hippocampal network changes following mindfulness training in tobacco vaping 
adolescents
NIH Principal Investigator:
Betty Jo Salmeron, MD, MA
Neuroimaging Research Branch
National Institute on Drug Abuse
BG BRC RM 07A717
251 Bayview Blvd
Baltimore, MD 21224
Phone: 667-312-5266
E-mail: bsalmeron@mail.nih.gov 
Fax: 443-740-2816

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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................1
STATEMENT OF COMPLIANCE ............................................................................................6
1
PROTOCOL SUMMARY....................................................................................................7
1.1
Synopsis.....................................................................................................................7
1.2
Schema.......................................................................................................................9
1.3
Schedule of Activities..............................................................................................10
2
INTRODUCTION ..............................................................................................................12
2.1
Study Rationale........................................................................................................12
2.2
Background..............................................................................................................12
2.3
Risk/Benefit Assessment .........................................................................................16
2.4
Known Potential Risks ............................................................................................16
2.5
Known Potential Benefits........................................................................................16
2.6
Assessment of Potential Risks and Benefits............................................................17
3
OBJECTIVES AND ENDPOINTS....................................................................................17
4
STUDY DESIGN ...............................................................................................................18
4.1
Overall Design.........................................................................................................18
4.2
Scientific Rationale for Study Design .....................................................................19
4.3
Justification for Intervention....................................................................................19
4.4
End-Of-Study Definition .........................................................................................19
5
STUDY POPULATION.....................................................................................................20
5.1
Inclusion Criteria .....................................................................................................20
5.2
Exclusion Criteria ....................................................................................................20
5.3
Inclusion of Vulnerable Participants .......................................................................21
5.4
Participation of NIH Staff or family members of study team members..................21
5.5
Inclusion of Pregnant Women, fetuses or neonates.................................................21
5.6
Lifestyle Considerations ..........................................................................................21
5.7
Screen Failures.........................................................................................................21
5.8
Strategies for Recruitment and Retention................................................................22
5.9
Costs ........................................................................................................................22
5.10
Compensation ..........................................................................................................22

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STUDY INTERVENTION ................................................................................................24
6.1
Study Interventions(s) or Experimental Manipulations(s) Administration .............24
6.2
Study Intervention or Experimental Manipulation Description ..............................24
6.3
Administration .........................................................................................................24
6.4
Fidelity.....................................................................................................................24
6.5
Interventionist Training and Tracking.....................................................................24
6.6
Measures to Minimize Bias: Randomization and Blinding.....................................24
6.7
Study Intervention/Experimental Manipulation Adherence....................................24
6.8
Concomitant Therapy ..............................................................................................25
6.9
Rescue Therapy .......................................................................................................25
7
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION 
AND PARTICIPANT DISCONTINUATION/WITHDRAWAL.............................................25
7.1
Discontinuation of Study Intervention/Experimental Manipulation .......................25
7.2
Participant Discontinuation/Withdrawal from the Study ........................................25
7.3
Lost to Follow-up ....................................................................................................25
8
STUDY ASSESSMENTS AND PROCEDURES..............................................................26
8.1
Screening Procedures...............................................................................................26
8.1.1
Screening activities performed prior to obtaining informed consent ......................26
8.1.2 Screening activities performed after a consent for screening has been signed.............26
8.2
Study Evaluations & Procedures after eligibility has been determined. .................26
8.3
Safety Assessments..................................................................................................30
8.4
Adverse Events and Serious Adverse Events ..........................................................30
8.4.1
Definition of Adverse Event....................................................................................30
8.4.2
Definition of Serious Adverse Events (SAE) ..........................................................30
8.4.3
Classification of an Adverse Event..........................................................................31
8.4.4
Time Period and Frequency for Event Assessment and Follow-Up........................32
8.4.5
Adverse Event Reporting.........................................................................................33
8.4.6
Serious Adverse Event Reporting............................................................................33
8.4.7
Events of Special Interest ........................................................................................34
8.4.8
Reporting of Pregnancy ...........................................................................................34
8.5
Unanticipated Problems...........................................................................................34
8.5.1
Definition of Unanticipated Problems (UP) ............................................................34

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8.5.2
Unanticipated Problem Reporting ...........................................................................34
9
STATISTICAL CONSIDERATIONS ...............................................................................34
9.1
Statistical Hypothesis...............................................................................................34
9.2
Sample Size Determination .....................................................................................35
9.3
Populations for Analyses .........................................................................................35
9.4
Statistical Analyses..................................................................................................35
9.4.1
General Approach....................................................................................................35
9.4.2
Analysis of the Primary Endpoints..........................................................................36
9.4.3
Analysis of the Secondary Endpoint(s) ...................................................................37
9.4.4
Safety Analyses .......................................................................................................37
9.4.5
Baseline Descriptive Statistics.................................................................................38
9.4.6
Planned Interim Analyses........................................................................................38
9.4.7
Sub-Group Analyses................................................................................................38
9.4.8
Tabulation of individual Participant Data................................................................38
9.4.9
Exploratory Analyses...............................................................................................38
10
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ......38
10.1
Informed Consent Process .......................................................................................38
10.1.1
Consent/Assent Procedures and Documentation.....................................................38
10.1.2
Consent for minors when they reach the age of majority........................................40
10.1.3
Considerations for Consent of NIH staff, or family members of study team members
41
10.1.4
Consent of Subjects who are, or become, decisionally impaired ............................41
10.2
Study Discontinuation and Closure .........................................................................41
10.3
Confidentiality and Privacy .....................................................................................42
10.3.1
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing 
Policies 42
10.3.2
Certificate of Confidentiality...................................................................................42
10.4
Future use of Stored Specimens and Data ...............................................................43
10.5
Safety Oversight ......................................................................................................43
10.6
Clinical Monitoring .................................................................................................44
10.7
Quality Assurance and Quality Control...................................................................44
10.8
Data Handling and Record Keeping........................................................................44

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10.9
Protocol Deviations and Non-Compliance ..............................................................45
10.10
Human Data Sharing, including Genomic Data Sharing, and Publication..............45
10.10.1 NIH Data Management and Sharing Policy and NIH Genomic Data Sharing Policy 
Compliance............................................................................................................................45
10.10.2 NIH Public Access Policy Compliance ...................................................................45
10.11
Collaborative Agreements .......................................................................................45
10.12
Agreement Type ......................................................................................................46
10.13
Conflict of Interest Policy........................................................................................46
11
ABBREVIATIONS ........................................................................................................46
12
REFERENCES................................................................................................................47

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STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Council for Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.

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1
PROTOCOL SUMMARY
1.1
Synopsis
Title:
Hippocampal network changes following mindfulness training in 
tobacco vaping adolescents in an open-label, pilot study.
Study Description:
This protocol will use fMRI and in-person and technology-delivered 
mindfulness-based stress reduction (MBSR) training to elucidate 
neurobehavioral correlates of regular nicotine vaping in adolescents 
compared to non-vaping adolescents, and changes in these correlates 
after MBSR training. Our central hypothesis is that nicotine vaping in 
adolescents will be associated with impaired hippocampal 
connectivity with large-scale brain networks (e.g., Executive Control 
network (ECN), Default Mode Network (DMN), Salience Network 
(SN)) involved in cognitive control and emotion regulation and 
decreased state transitions (measured via dynamic resting state 
functional connectivity (rsFC)); and that MBSR training will increase 
hippocampal connectivity to ECN and alter time in state and state 
transitions in frequent vaping adolescents, with these rsFC changes 
predicting changes in vaping behavior.   
Objectives:
Primary Objectives:
(1) To characterize static and dynamic rsFC of hippocampal 
networks in frequent nicotine vaping adolescents compared to non-
vaping adolescents.
(2) To characterize rsFC changes in hippocampal networks following 
an in-person and technology-delivered MBSR training program in 
frequent nicotine vaping adolescents.
Secondary Objectives:
-
To assess engagement with a smoking cessation app and 
changes in vaping behavior, emotion and cognition in the 3 
months following MBSR training. 
-
To assess differences between vaping and non-vaping teens  
pre- and post-MBSR training on other measures of network 
connectivity. 
Endpoints:
Primary Endpoints:
-
(1) Seed-based rsFC between hippocampal seed regions and 
large-scale brain networks (DMN, ECN, SN) and dynamic-
rsFC measures in 40 nicotine vaping and 40 non-vaping 
youth.
-
(2) Seed-based rsFC between hippocampal seed regions and 
large-scale brain networks (DMN, ECN, SN) and dynamic-
rsFC measures within the nicotine vaping group Pre/Post 
MBSR training.
Secondary Endpoint: 

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Engagement with MBSR training and post-training Craving-
to-Quit app and change scores for other behavioral measure 
(e.g. vaping, emotion regulation).
-
rsFC from seeds such as dorsal anterior cingulate. 
Study Population:
40 nicotine vaping adolescents (13-18 years old) who vape 4-
7 days per week, and 40 age, sex, race/ethnicity, SES matched 
typically developing (TD) adolescents with no nicotine 
vaping/tobacco smoking history. Participants will be recruited 
via online advertising, word of mouth, and from our vaping 
survey study. Recruitment will target the greater Baltimore 
area. To improve generalizability of our results, we will 
include youth who vape and who also smoke cigarettes (dual 
users) or co-use cannabis (co-MJ users) as well as those with 
stable psychiatric comorbidities. We will measure, control 
for, and exploratorily examine differences in these behaviors 
and groups in our analyses. 
Phase or Stage:
This is a natural history study (comparison of teens who do and do not 
vape) and an open-label pilot study (comparison of teens who vape 
before and after MBSR training).
Description of 
Sites/Facilities 
Enrolling 
Participants:
The Biomedical Research Center of NIDA-IRP in Baltimore, MD, is 
the single site used for this study. 
Description of Study 
Intervention:
The study intervention is a 9-week MBSR intervention once per week 
in-person or remotely (via an NIH approved remote platform used in 
compliance with policy, including HRPP Policy 303). The MBSR will 
be delivered to groups of 8-12 participants. Only the vaping 
adolescents will receive MBSR training. 
Study Duration:
The study duration is approximately 24 months. 
Participant 
Duration:
The participant duration is approximately 5.5-7 months, including 
baseline assessment and MRI scan 1, the 9-week MBSR intervention, 
and post-intervention assessment and MRI scan 2. There will also be 
a monthly follow-up for three months after the last MRI scan. Non-
vaping participants will only complete baseline assessments and scan 
1, which should take a week or less.  

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1.2
Schema

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1.3
Schedule of Activities
Procedures
Pre-screening 
(Pre-consent)
Visit(s) 1
Visits 2-10
Visit 11
 
  
Visits 12-15
Eligibility Questionnaire 
Review 
X
X
-
-
-
Informed Consent
-
X
-
-
-
Demographics
X
X
-
-
-
Clinical history
X
X
-
-
-
Nursing Eval 
-
X
-
X
X
Outcome Evaluation
-
-
-
-
MRI scan
-
X
-
X
-
Questionnaires
-
X
-
X
X
MBSR training
-
-
X
-
-
Adverse Events 
Reporting
-
X
X
X
X

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TABLE 1. DIAGNOSTIC MEASURES AND ASSESSMENT BATTERY 
Visit #* 
DOMAIN 
INSTRUMENT(S) 
#1 
#2-10 
#11
#12-
15 
Diagnostic 
Assessment 
Mini International Neuropsychiatric Interview for Children 
and Adolescents-DSM-5.0 version (MINI-KID-5) or SCID-
RV 
X 
 
 
Demographics 
and Puberty 
Demographics questionnaire and Pubertal Development Scale  
X 
 
MRI Safety
MRI Safety Assessment
X
X
General Substance Use: Timeline Follow-back (TLFB) - 28 
Days (V1), 7 Days (V12-15): tobacco vaping (vaping days and 
vapes or puffs/day), tobacco smoking, cannabis, alcohol, other 
drugs; Substance Use History Questionnaire; Cannabis Use 
Disorder  Test (CUDIT); Craving Questionnaire
X 
 
X 
E-Cigarette Measures (Vapers only):  E-Cigarette Dependence 
Scale (EDS, 4 items); Modified Fagerstrom Test for Nicotine 
Dependence (FTND); Nicotine Social Influence Questionnaire 
(NSIQ)
X 
 
 
 
X 
Substance Use 
Measures
 
 
Biospecimens: Urine Cotinine Test, Urine Drug test (UDT), 
Breath CO and ALC tests 
X 
X
X 
Psychological 
Measures 
Sensitivity to Reward and Sensitivity to Punishment 
Questionnaire (SRSPQ), Patient Health Questionnaire-9 
(PHQ-9), General Anxiety Disorder-7 (GAD-7), Difficulty in 
Emotion 
Regulation 
Scale, 
5-trial 
Adjusting 
Delay 
Discounting Task (bench), Momentary Impulsivity Scale 
X 
X 
Mindfulness 
Measures 
Five-Facet Mindfulness Questionnaire (FFMQ), Mindfulness 
Practice Questionnaire (MPQ) (Visits #3-15 only) 
X 
X (MPQ 
only) 
X 
Cognitive 
Measures 
Digit Span (DGS) assessment (forward and backwards) 
X
 
X 
*Note: Visit(s) 1 = Baseline Assessment and MRI scan 1 but may be split into two to four visits (some of which 
may be conducted virtually) ~0-3 months pre-MBSR intervention; Visits 2-10 = MBSR training; Visit 11 = MRI 
scan 2 ~0-6 weeks post-MBSR intervention; Visits 12-15 (starting within about 3 weeks post-MBSR training) = 
monthly follow-up visits (preferably in-person but virtual, if need be); Visit 11 may be combined with Visit 12 
or 13 or done separately.

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2
 INTRODUCTION
2.1
Study Rationale
Tobacco use remains the leading cause of preventable morbidity and mortality worldwide and 
rates of tobacco use are rising among U.S. teens (primarily via vaping), erasing two decades of 
progress in prevention.1 While substantial evidence indicates that tobacco smoking is associated 
with dysfunction in brain networks involved in emotion regulation, attention, and reward 
processing2,3, the developmental effects of chronic nicotine exposure via vaped tobacco, which 
lacks exposure to the many toxins in smoke, are not well understood.4  Findings from research 
programs at NRB/NIDA-IRP and Johns Hopkins have established that: (1) adult tobacco smoking 
phenotypes are associated with alterations in cortico-striatal-limbic network connectivity2,5-7, and 
(2) adolescent nicotine exposure results in disruptions to feedback-related neurophysiological 
processes in humans10-12 and connectivity in hippocampal networks central to emotion regulation 
in rodents.13  
Mindfulness training (MT) appears to induce network-level changes in overlapping brain 
regions and networks in a manner that is opposite to the effects of adolescent tobacco exposure.14  
Meaningful associations have been shown between MT, mindfulness practice, and affective 
outcomes.15,16  Further, the theoretical underpinnings and psychological mechanisms of 
mindfulness fit well with and target factors believed to be central to recovery from addiction (e.g. 
emotion regulation).17  Little is known about the neurobehavioral mechanisms of MT on tobacco 
vaping or smoking in youth.  Recent innovations in functional magnetic resonance imaging (fMRI) 
using resting-state functional connectivity (rsFC) allow for system-level investigations of brain 
function. 
The purpose of this translational bench-to-bedside study is to examine the neurobiological 
effects of an evidence-based technology-delivered MT program on vaping-related rsFC alterations 
in hippocampal networks and testing whether changes in rsFC (ΔrsFC) in these networks predict 
reduction in tobacco vaping behaviors in adolescents.  The study also aims to test the accessibility 
and feasibility of using this MBSR platform as an implementation for widespread MT in 
adolescents.
2.2
Background 
Resting-state functional connectivity and translational neuroscience in addiction.18  rsFC 
quantifies correlations in low frequency fluctuations in blood-oxygen-level-dependent (BOLD) 
fMRI signal between disparate brain regions at rest.19  Static rsFC (s-rsFC) assessed over many 
minutes, allows for quantification of the strength of connectivity within and between large-scale 
brain networks.  In contrast, dynamic rsFC (d-rsFC) characterizes time-varying fluctuations in FC 
on the order of seconds and provides a global index of ‘dynamic network flexibility’, quantifying 
time spent in each network configuration (brain state) and how often network configurations 
change.20  In combination, these approaches enable the investigation of changes in spatial and 
temporal variance in networks as they relate to disease processes and in response to 
interventions.21,22  rsFC/fMRI approaches provide unique translational and reverse translational 
potential, since fMRI measures the same biophysical signal and as homologous networks have 
been identified using rsFC across species.23  This study is highly translational: It uses rsFC (static 
and dynamic) to investigate whether findings from a rsFC fMRI study conducted in rats that 

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showed hippocampal network alteration following adolescent nicotine exposure are replicable in 
human adolescents and show ΔrsFC following a MT intervention. 
Adolescent Neurodevelopment, Vaped vs. Smoked Tobacco Exposure, & Treatment Options  
Adolescent Nicotine Exposure Disrupts Development of Hippocampal-centered Circuits and 
Negatively Impacts Long-term Cognitive and Emotional Outcomes.  Adolescence is a critical 
development stage marked by dynamic shifts in brain and behavior.  It also is a vulnerable period 
for the initiation of drugs, with tobacco being among the mostly frequently used.24  Cholinergic 
signaling modulates the programming of synaptic circuits and influences neurocognitive 
development. Exposure to nicotine and tobacco smoke during adolescence can disrupt these 
neurocognitive processes.  Animal studies show that chronic nicotine exposure during adolescence 
alters nicotine acetylcholinergic receptor (nAChR) expression and negatively impacts maturation 
of hippocampal and cortico-striatal-limbic circuits leading to dysregulation of cholinergic, 
dopaminergic, and serotonergic neurotransmitter systems and long-lasting impairments in 
learning, memory, and attention and depression-like behaviors.25-29  The hippocampus, with its 
high expression of nAChRs, appears to be distinctly sensitive to the developmental effects of 
chronic nicotine exposure.30  Recent findings from a series of rodent studies by Gould and 
colleagues (summarized in 31) show that nicotine exposure during adolescence disrupts 
hippocampal development and produces long-term structural and functional hippocampal 
modifications that translate to persistent hippocampus-dependent cognitive and affective deficits.  
Despite the translational potential, there are few developmentally-focused drug exposure rsFC 
fMRI studies in rodents.  Our group recently completed the first rodent study to characterize the 
developmental effects of chronic nicotine exposure on whole-brain rsFC by chronically exposing 
adolescent and adult rats to nicotine and conducting serial fMRI scans. Preliminary results from 
this study show divergent effects of nicotine exposure on prelimbic (PrL) brain circuitry that varied 
as a function of developmental stage and identified distinct alterations in hippocampal 
connectivity that were unique to rodents chronically exposed to nicotine during adolescence.13   
Human Studies:  In clinical studies, adolescent tobacco smokers experience cognitive deficits 
which are exacerbated during acute nicotine withdrawal and are more than twice as likely to 
develop depression by their late 20’s.32,33  While understudied, results from the human 
neuroimaging literature largely parallel preclinical findings. Adolescent tobacco smokers 
(compared to non-smokers) exhibit alterations in hippocampal and cortico-striatal-limbic circuits 
that map onto executive control (ECN), default mode (DMN), and salience (SN) brain networks, 
and show notable structural, functional, and connectivity alterations in diverse brain regions 
enriched for nAChRs including the hippocampus, prefrontal cortex, insula, anterior cingulate 
(ACC), posterior cingulate (PCC), parietal cortex, cerebellum, thalamus, and striatum.11,12,34-38 
Are the Developmental Effects of Vaped Nicotine Similar to Those of Smoked Tobacco?
 Little is known about the effects of vaped nicotine on brain function and connectivity in humans 
and no neuroimaging studies have been conducted in young people who chronically vape nicotine.  
At the time of proposal submission three studies have been published examining the effects of 
nicotine vaping in humans (all in adults).  Acute administration of vaporized nicotine appears to 
alter the BOLD fMRI signal in the same nAChR-enriched brain regions that cigarette smoke 
inhalation does.39,40 In the first fMRI study conducted in chronic e-cigarette using adults, Nichols 
et al.41 found evidence for changes in brain activity in response to vaping cues in the 

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parahippocampal gyrus, PCC, precuneus, fusiform gyrus, lingual gyrus, thalamus, and cerebellum 
along with multiple parietal, temporal, and occipital regions. Given the rising rates of nicotine 
vaping and conflicting messages about the comparative health risks from vaping and smoking, it 
is of critical importance to determine the effects of vaped and smoked tobacco on brain 
development and cognitive and emotional outcomes.  
Tobacco vaping has tripled among U.S. adolescents and few treatment options exist for 
young people who develop a vaping-related tobacco use disorder (TUD).42  In 2018, 4.1 million 
teens, more than one out of every four U.S. high school students, reported current tobacco product 
use, with 21% of those teens reporting use of nicotine via vaping (e-cigarettes).15  E-cigarette use 
is strongly associated with other tobacco product use (e.g. two-thirds of teen tobacco users are dual 
users who engage in both vaping and smoking).43  In tobacco-naïve teens, vaping nicotine is 
associated with increased risk for progression to smoking.44,45  Further, use of e-cigarettes has not 
been shown to aid in smoked tobacco cessation in youth.46  Compounding this issue, evidence-
based treatment (EBT) options are limited for adolescents who vape nicotine and develop 
TUD.42,47  No clinical guidelines exist and few interventions have been developed for this 
population. Development and testing of new treatments for youth TUD are desperately needed 
given the modest efficacy of current EBT for youth smoking48 and lack of EBT targeting nicotine 
vaping in youth.      
Mindfulness Training: Neural Correlates, Psychological Mechanisms, & Role in Tobacco 
Cessation 
Mindfulness is defined as “present-focused, non-judgmental awareness”.49  Over the past two 
decades, numerous studies have shown that mindfulness can be increased with training and 
practice with resultant reductions in distress and improvements in emotion regulation.16 
Furthermore, mindfulness training (MT) produces salutatory changes in brain structure, function, 
and connectivity.14  Given its ability to target distress tolerance and emotion regulation (two 
psychological phenotypes closely linked to treatment response for SUD/TUD), there is growing 
interest in adapting mindfulness-based interventions for use in TUD populations.50   
Neurobiological Models of Adolescent TUD and Mindfulness Identify Overlapping Neural 
Circuitry.  Neuroimaging studies in adults have reliably shown changes in the hippocampus, 
ACC, PCC, insula, supramarginal gyrus (SMG), and PFC along with DMN, ECN, and SN 
networks following MT and practice.14,51-58  These brain regions/networks show significant 
anatomic overlap with the brain regions/networks showing evidence of dysfunctional signaling in 
tobacco using youth.35-37  Of significant relevance to our proposal, impairments in hippocampal-
prefrontal circuits are observed in TUD samples30 and are strengthened in non-smokers following 
MT.59,60 Additionally, in d-rsFC studies, tobacco smoking adults show altered d-rsFC with fewer 
state transitions during abstinence61,62; Conversely MT is associated with increased state 
transitions in non-smoking adolescents and adults.63,64  Taken together, these findings indicate that 
MT impacts neural function, connectivity, and flexibility in a manner that is opposite to the effects 
of chronic tobacco exposure, suggesting a possible brain mechanism via reversal or 
‘normalization’ of dysfunctional networks.  Janes et al.65 recently showed that smartphone app-
delivered MT reduced cue-induced PCC activity with the magnitude of reduction in PCC activity 
predicting concurrent decline in smoking in adults.  Alternatively, MT could improve abstinence 
via compensatory or training mechanisms by strengthening connectivity in unaffected networks.  

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In this pilot study we will investigate whether measures of s-rsFC and d-rsFC in circuits altered 
by chronic nicotine exposure are modulated by MT and characterize how such rsFC changes 
relate to vaping behavior.  
Psychological Mechanisms of Mindfulness Training: Awareness & Emotion Regulation  
Participation in MT leads to reduction in anxiety and depression, improved coping, pain 
management, and emotion regulation.16  Much of the published literature on MT refers to the 
mindfulness-based stress reduction (MBSR) program, a 9-week program which focuses on 
experiential instruction of a variety of techniques and discussion of mindfulness concepts designed 
to enhance participants’ innate mindfulness.49,66  In contrast to cognitive therapies which focus on 
changing the content of thoughts, MBSR targets enhancing non-judgmental awareness of one’s 
own present-moment experiences (thoughts, feelings, sensations, and reactions) as they occur.17 
In this way, MBSR increases awareness of life moment-by-moment as it unfolds and seems to 
enhance the process of self-regulation in an on-going manner.  Meta-analytic work with adult 
MBSR studies suggests a role for emotion regulation mechanisms of reduced cognitive and 
emotional reactivity, increased mindful awareness, attention, and acceptance, and decreased 
rumination and worry.16,17,53  
Mindfulness Training shows Preliminary Effectiveness for Addictive Disorders.  Studies in 
addictive disorders suggest that MT programs including MBSR, mindfulness-based relapse 
prevention (MBRP)67, and mindfulness-oriented recovery enhancement (MORE)68 may reduce 
substance misuse and aid in drug abstinence in adults50,69, in part, by modulating cognitive and 
affective processes integral to cognitive control, emotion regulation, and reward processing53,70 
and decoupling substance use behavior (response) from craving and negative affect (trigger).71  
Few studies have examined the impact of MT on youth substance use.  
Technology-delivered Mindfulness Training has the potential to increase youth participation 
in TUD treatment.  As a result of the pandemic, technology-delivered healthcare has expanded 
dramatically. The use of digital technology for smoking cessation holds promise for adolescents 
who do not typically access traditional treatments. Over 75% of young people own or have access 
to a smartphone72 and two-thirds report using a health-related mobile app.73  Pbert et al.74 recently 
published findings from a feasibility study showing that smartphone app-based MT with 
CravingtoQuit® was effective at reducing tobacco smoking in adolescents and reductions in 
smoking were correlated with app engagement. We propose to test engagement with this 
technology-delivered mindfulness-based cessation app after the group-based MT delivered via on-
site or virtual sessions.  
Need for Mechanism-focused Translational Research related to Mindfulness and Youth 
Vaping.   Although, substantial evidence has accumulated regarding the negative health effects 
and neural correlates of smoked tobacco products in youth and the beneficial effects of mindfulness 
and MBSR in adults, these phenomena are understudied in youth and in relation to vaped tobacco.  
This pilot study seeks to elucidate neurobehavioral correlates of daily tobacco vaping in 
adolescents, focused on static and dynamic rsFC, and to characterize the impact of participation in 
a MBSR intervention on rsFC and vaping behaviors.  This pilot study is among the first to target 
vaping-related TUD in adolescents42 and will provide feasibility, acceptability, and preliminary 
efficacy data for MBSR which will inform next stage-controlled trials.   As tobacco vaping youth 
represent a large, underdiagnosed, and vulnerable population75, this protocol may elucidate the 

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potential negative impact of chronic tobacco vaping on brain function and connectivity (albeit 
through a cross sectional comparison with non-vaping adolescents) and potential beneficial neural 
changes in brain networks related to MBSR in the setting of adolescent development.  These 
findings will improve our understanding of the neural mechanisms through which MBSR may 
promote tobacco cessation in youth (i.e., via compensatory or training mechanisms in unaffected 
regions, ‘normalization’ of vaping-associated circuit abnormalities, or both).  In addition, network 
changes may be useful (and potentially more sensitive) indications of MBSR intervention effects, 
which may inform iterative changes to MBSR to optimize it for clinical care.55 This Bench-to-
Bedside (BtB) study will translate novel findings related chronic nicotine exposure during 
development from a rat study (bench) to humans receiving treatment (bedside). In doing so it will 
improve our understanding of an important disease process (i.e., tobacco vaping) and aid in the 
pilot testing and mechanistic understanding of a new therapeutic intervention for vaping-related 
TUD in youth (i.e., MBSR). 
Preliminary data comes from 3 domains: (1) Adolescent tobacco use:  Animal studies: Cited above, 
our research team recently showed rsFC alterations in hippocampal-PrL neural circuitry in rodents 
with chronic adolescent nicotine exposure.76  Human Studies: Studies using multimodal 
neuroimaging (i.e., EEG, fMRI) have characterize cognitive and affective correlates of addiction 
severity and treatment response in adolescent substance users.11,77,78 This work identified altered 
feedback-related negativity, P2, P300, and theta oscillatory EEG signals in tobacco smoking 
adolescents that were correlated with self-report measures of tobacco addiction, withdrawal, and 
taste/flavor smoking motives.10-12,79,80 (2) Mindfulness treatment studies:  Sibinga and others, 
(2011-2018) have conducted multiple RCTs of MBSR in diverse youth populations.  Across 
studies, her research has shown that participation in MBSR leads to improvements in 
psychological symptoms and health behaviors in at-risk urban youth.81-84  (3) Neural correlates of 
Successful Tobacco Cessation and Mindfulness Practice:  Hammond et al (2019) completed a 
meta-analysis showing functional alterations in the ACC, inferior frontal gyrus, SMG, precuneus, 
putamen, and temporal brain regions that were associated with SUD treatment response in addicted 
youth (including tobacco smokers).85  Drs. Ross, Yang, and Hammond recently completed a fMRI 
study showing that adult tobacco smokers who relapsed following a cessation intervention 
(compared to abstainers) had fewer d-rsFC between-state transitions.86  Lastly, prior work from 
Dr. Yang showed increased ACC activity and white matter integrity between the ACC and brain 
regions implicated in self-control following a 4-week MT program.87,88  
2.3
Risk/Benefit Assessment
2.4
Known Potential Risks
For both non-vaping control and vaping adolescent participants, there is minor risk associated with 
the MRI scans, including injury associated with bringing magnetic objects too close to the scanner, 
temporary hearing loss and very rarely minor burns. Trained personnel repeatedly screen 
participants and monitor use of earplugs to mitigate the risk of injury related to the strong magnetic 
field and noise from the scanner.
For vaping teens receiving the MBSR intervention, there is risk of breach of confidentiality 
associated with the group participation activities of the MBSR program.
2.5
Known Potential Benefits

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For non-vaping controls, there are no direct benefits to the individual participant. However, there 
is an extended benefit to society as their participation will aid in a better understanding of the 
adolescent brain in relation to developing a nicotine use disorder.
Vaping teens will all receive the MBSR intervention and thus its potential benefits, including 
decrease in anxiety and depression and enhanced self-regulation. These psychological changes 
could lead to reduced vaping-related substance use.
2.6
Assessment of Potential Risks and Benefits
The risks associated with the MRI scans are low, and the benefits of the MBSR training to the 
vaping teens combined with the benefits to society via greater understanding of the adolescent 
brain mitigate the potential risks.
3
OBJECTIVES AND ENDPOINTS
 
OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
Primary
(1) To characterize static 
and dynamic rsFC 
differences in 
hippocampal networks 
related to nicotine 
vaping in adolescents.
(2) To characterize rsFC 
changes (ΔrsFC) in 
hippocampal networks 
and d-rsFC following a 
technology-delivered 
MBSR program in 
nicotine vaping 
adolescents.
(1) Seed-based s-rsFC 
between hippocampal 
seed regions and 
large-scale brain 
networks (DMN, 
ECN, SN) and d-rsFC 
measures comparing 
time in state and state 
transition probabilities 
between N=40 
nicotine vaping and 
N=40 non-vaping 
youth.
(2) Seed-based s-rsFC 
analysis between 
hippocampal seed 
regions and large-scale 
brain networks (DMN, 
ECN, SN) and d-rsFC 
measures (time in state 
and state transition 
probabilities) within 
the frequent nicotine 
(1) Hippocampal 
networks are related 
to nicotine exposure, 
especially in 
adolescence.
(2) Hippocampal 
connectivity and d-
rsFC measures are 
related to both 
nicotine exposure 
and MBSR training.

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vaping group Pre/Post 
MBSR.
Secondary
(1) To assess engagement with 
a smoking cessation app 
and changes in various 
behaviors following MBSR 
training.  
(2) To assess other imaging 
metrics such as resting 
connectivity from 
alternative sites related to 
mindfulness meditation 
and nicotine dependence 
(e.g., dACC) between 
vaping and non-vaping 
teens and pre-/post-MBSR 
training in vaping teens. 
(1) Engagement with apps 
and Δscores for each 
behavioral measure 
(e.g., vaping behavior, 
emotion regulation, 
cognitive function) in 
the within-subject 
analyses of adolescents 
who vape, undergoing 
MBSR training.
(2) Connectivity metrics. 
(1) Understanding 
feasibility and 
acceptability as well 
as efficacy is 
important in 
assessing potential 
for development of 
MBSR training as a 
new therapeutic 
intervention for 
vaping-related TUD 
in youth.
(2) These metrics will 
provide a fuller 
understanding of 
teen vaping and the 
effects of MBSR 
training.
4
STUDY DESIGN
4.1
Overall Design
This is natural history study (comparison of vaping to non-vaping adolescents) and an open label 
pilot study (MBSR intervention to vaping adolescents).
This single-sight study will be carried out at the NIDA-IRP’s Biomedical Research Center in 
Baltimore, MD.
The study will enroll up to 60 nicotine vaping youth and 60 non-vaping youth to obtain complete 
data on N=40 tobacco vaping youth 13-18 years old and N=40 age, sex, race/ethnicity, SES 
matched typically developing (TD) non- vaping/non-smoking youth. The study intervention, given 
to vaping teens, is a Mindfulness-Based Stress Reduction (MBSR) training. The intervention is a 
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The MBSR intervention will consist of eight weekly 2-hour sessions and one 3-hour retreat that 
will take place at the NIDA BRC. Each group will consist of 8-12 participants. 
Participants will be recruited online and via our concurrent vaping survey study.  Only nicotine 
vaping youth will participate in the MBSR intervention. The vaping group will participate in one 
to four primary data gathering visits, all but one of which can be done virtually. The visit that will 
include the first MRI scan visit must take place in-person 0-3 months pre-MBSR intervention, and 
the second MRI scan visit will take place 0-6 weeks post-MBSR intervention. The TD non-vaping 
group will not participate in the MBSR intervention, and therefore will only participate in the 
baseline assessments (one to four virtual or in-person visits including the first in-person MRI scan). 
For those receiving the MBSR intervention, there will also be four monthly follow-up visits which 
may be administered in-person or virtually. The one at the conclusion of MBSR training may be 
combined with scan 2. The MBSR visits are optional, and as long as one visit is completed, the 
other visits if missed will not result in a deviation.
We hypothesize that teens who vape will differ from those who do not on all behavioral, cognitive 
and imaging measures and that the MBSR intervention will alter these measures in the vaping 
teens so that they will differ less from their non-vaping counterparts. 
4.2
Scientific Rationale for Study Design
The non-vaping group MRI will serve as a comparison against the frequent nicotine vaping group 
to characterize static and dynamic rsFC alterations in hippocampal networks related to frequent 
nicotine vaping in adolescents (Objective 1). Frequent nicotine vaping adolescents will participate 
in two MRI scan visit days (pre- and post- MBSR intervention) to characterize rsFC changes 
(ΔrsFC) in hippocampal networks following the intervention (Objective 2).
4.3
Justification for Intervention
As discussed in section 2.2, MBSR engages brain regions involved in tobacco use disorder. Sibinga 
and others, (2011-2018) have conducted multiple RCTs of MBSR in diverse youth populations.  
Across studies, her research has shown that participation in MBSR leads to improvements in 
psychological symptoms and health behaviors in at-risk urban youth.81-84    We will use the same 
9-week MBSR treatment protocol and the same MBSR trainer as previously used in these studies 
conducted in similar populations in the Baltimore area. 
4.4
End-Of-Study Definition
A frequent nicotine vaping participant is considered to have completed the study if they have 
completed the baseline assessment, all 9 weeks of the MBSR intervention, the pre- and post-
intervention MRI scans, and the follow-up assessments. There will be an end of intervention 
assessment and three follow-up assessments (once per month for three months and may be 
conducted virtually) after the last MRI scan. The final follow-up marks the end of the study for the 
participant.
A non-vaping participant is considered to have completed the study if they have completed the 
baseline assessment and one MRI scan. 
(SoA), Section Error! Reference source not found..

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5
STUDY POPULATION
5.1
Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
Non-Vaping group:
1. For adolescents aged 17 and under, parental/guardian informed consent to participate in 
the study
2. English language fluency
3. Males and females; Age 13-18 enrolled in grades 9-12, or the summer after graduation.
4. No MRI contraindications
5. No evidence of current psychosis, mania, or significant suicidality 
6. If on medication for depression, anxiety or ADHD, dose has been stable for 3 months
7. No DSM-5 diagnosis of moderate or severe SUD related to a psychoactive substance, 
including tobacco, in the past year
8. Access to necessary resources for participating in a technology-based intervention, which 
includes smartphone ownership for this study
9. No use of nicotine more than 5 times in their life, and none at all in the last 30 days prior 
to enrollment.
  
Vaping group:
1. For adolescents aged 17 and under, parental/guardian informed consent to participate in 
the study
2. English language fluency
3. Males and females; Age 13-18 enrolled in grades 9-12, or the summer after graduation.
4. No MRI contraindications
5. No evidence of current psychosis, mania, or significant suicidality 
6. If on medication for depression, anxiety or ADHD, dose has been stable for 3 months
7. No DSM-5 diagnosis of moderate or severe SUD related to another psychoactive substance 
(other than tobacco) in the past year
8. Vape a nicotine containing product at least 10 days in the past 30 days 
9. Access to necessary resources for participating in a technology-based intervention, which 
includes smartphone ownership for this study
5.2
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this 
study based on self and or parent-report unless otherwise noted: 
Vaping or Non-Vaping Group:
1. Chronic medical conditions associated with cerebral blood flow abnormalities per PI/MAI 
determination after review of the medical history.
2. Neurological conditions that may interfere with MRI data quality per PI/MAI 
determination after review of the medical history.

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3. Neurodevelopmental disorders that are likely to significantly affect data in the judgment of 
the MAI/PI
4. Non-penetrating traumatic brain injury with loss of consciousness > 30 minutes or 
significant sequalae persisting longer than 2 weeks or any penetrating traumatic brain 
injury.
5. Changing dose of psychotropic medication in past 3 months
6. Current regular meditation or yoga practice averaging >10 min/day for >2 days per week
7. Pregnancy, self-report upon protocol entry, but by urine test prior to MRI scan.
5.3
Inclusion of Vulnerable Participants
We will include children because this study focuses on effects of vaping unique to adolescents.
Non-English speakers are excluded because the questionnaires in this study are not all validated 
in languages other than English. We do not have the resources to translate the consent and 
questionnaires.
5.4
Participation of NIH Staff or family members of study team members
NIH staff and family members of study team members may be enrolled in this study.  Neither 
participation nor refusal to participate as a subject in the research will have an effect, either 
beneficial or adverse, on the participant’s employment or position at NIH.
Every effort will be made to protect participant information, but such information may be available 
in medical records and may be available to authorized users outside of the study team in both an 
identifiable an unidentifiable manner.
The NIH Frequently Asked Questions (FAQs) for Staff Who are Considering Participation in NIH 
Research and Leave Policy for NIH Employees Participating in NIH Medical Research Studies 
(NIH Policy Manual 2300-630-3) will be provided to subjects for them to review.  Please see 
section Error! Reference source not found. for consent of NIH Staff.
5.5
Error! Reference source not found.Inclusion of Pregnant Women, fetuses or neonates
Pregnant women may not participate in this study.
5.6
Lifestyle Considerations
Participants will be instructed to abstain from cannabis, alcohol, and other street drugs for 24 hours 
and limit caffeine for 12 hours, prior to scan visits, but will be allowed to vape as usual. Abstinence 
will be verified on scan days via self-report, and UDT, with participants rescheduled if they test 
positive for THC or other drugs on UDT and fail a clinical assessment for intoxication.  
Participants in the vaping group will need to agree to participate in the MBSR training.  One 
parent/guardian must be present for the consent process for participants under 18 y/o, and they will 
have the option to remain at NIDA while their minor is participating.
5.7
Screen Failures
Screen failures are defined as participants who consent to participate in this study but are not 
subsequently entered in the study. Individuals who do not meet the criteria for participation in this 
trial (screen failure) because of meeting one or more exclusion criteria that are likely to change 
over time may be rescreened. Examples include stabilization of antidepressant treatment of an 

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affective disorder resulting in three months stable dose without significant clinical symptoms. 
Rescreened participants will be assigned the same participant number as for the initial screening.
5.8
Strategies for Recruitment and Retention
Recruitment is generally conducted under the NIDA IRP Office of the Clinical Director (OCD). 
Recruiting materials may be developed in-house or by contractors. We may also use the service 
provided at the NIH Office of Patient Recruitment. All advertising methods will comply with the 
most current regulations (NIH and OHSRP guidelines) and the NIDA policy on recruitment 
materials and with Information Systems Security Officer (ISSO) approval for any IT-related tools 
or metrics to aid in or monitor recruitment. Digital ads link to the Prescreening Form on REDCap. 
Participants have the option of filling out the Screening Form independently, or leaving a number 
and receiving a call from the study team, to complete the form as a Phone Screen. Subjects may 
be recruited from the general population in the Baltimore region through advertising in city, 
regional or campus newspapers, social media and other online platforms (e.g., Craigslist), email 
and digital listservs, direct mail, local clubs and/or schools, and other media or via direct outreach 
and referrals. Please refer to the Recruiting Materials document for more information about 
recruitment methods. Participants may be recruited online and from the concurrent vaping survey 
study (IRB001196). Upon completion of the vaping survey study, participants are given the 
opportunity to share their contact information if they are interested in this study.
Community providers of care and services in Baltimore, Washington DC and the surrounding areas 
may be contacted for recruitment and IRB approved materials will be offered to these facilities. 
Additionally, some healthcare providers provide medical record recruitment services. These 
services include sending IRB approved notices to their potentially qualified patients, who have 
opted in for such messages, via their secure electronic patient portals (i.e., medical record) to let 
them know there is a research study for which they may qualify. If they are interested, patients will 
indicate that their information can be sent to the study team. Potential participants may also be 
recruited from the NIDA IRP approved screening protocol.
NIDA IRP personnel may hand out IRB approved materials, meet potential candidates interested 
in studies and answer any questions they may have. As done for previous outreach events, we may 
take NIH issued, password-protected devices so that interested people can leave their information 
with us. We will work with IT staff to ensure this system is compliant with NIDA-IRPs ISSO and 
will comply with Privacy Act requirements. Typically, IT staff will create a database for outreach 
personnel to record candidate information directly so that they cannot see other people’s 
information. As a back-up, (e.g., battery failure) we may take index cards so that people can write 
down their information for us. Again, this method would eliminate the possibility that they would 
see anyone else’s information as we would give each person their own card.  
5.9
Costs
There are no costs to the participant and insurance will not be billed.
5.10 Compensation
Participants will be compensated according to NIDA IRP Remuneration Guidelines and following 
guidelines from NIH OHSRP Policy 302. Participant compensation rates are outlined in the table 
below. 

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Consent/Study 
Procedures: Rate = 
$20/hr
MRI: Rate 
= 
$25/scan
MBSR 
(parent/gu
ardian 
only) 
Follow
-Ups: 
Rate = 
$20/hr
Estimated 
TOTAL
Non-Vaping 
Participant
Consent/Screening/Ba
seline/MRI Visit ~5 - 
5.5 hrs = ~$100-$110
1 scan =
$25
N/A
N/A
~$125 - 
$135
Non-Vaping 
Participant 
Parent
Consent/Screening/Ba
seline/MRI Visit ~1 - 
5.5  hrs = ~$20 - $110
N/A
N/A
N/A
~$20 - 
$110
Vaping 
Participant
Consent/Screening/Ba
seline/MRI Visits ~ 7 - 
7.5 hrs = ~$140-$150
2 scans =
$50
travel 
reimburse
ment only
~4 
hrs= 
$80
~$270 - 
$280
Vaping 
Participant 
Parent
Consent/Screening/Ba
seline/MRI Visits ~ 1 - 
7.5 hrs = ~$20-$150
N/A
travel 
reimburse
ment only
~0-4 
hrs=
$0-$80
~$20 - 
$230
We anticipate non-vaping participants will earn about $125 - $135, while vaping participants will 
earn about $270 - $280, depending on the total time it takes for each participant to complete study 
procedures. If participants withdraw before completion of the study, they will be compensated 
only for the time/procedures completed. Time spent in MBSR training sessions will not be 
compensated, as there is potential for direct benefit from the MBSR training. 
One parent/guardian must be present for the consent process for participants under 18 y/o and one 
parent/guardian will be compensated $20/hr. They will have the option to remain at NIDA while 
their minor is participating. If so, they will be compensated $20/hour for their time, except for 
MBSR training time. 
We anticipate a non-vaping participant’s parent/guardian will earn up to about $110 if they stay at 
NIDA for all of the study procedures. 
We expect a vaping participant’s parent/guardian will earn up to about $230 if they attend all visits 
and remain at NIDA for all procedures. Note that neither parents nor participants are compensated 
for MBSR training visits due to potential of direct benefit to the teen. 
Additionally, travel will be provided or reimbursed for participants. Accompanied minors or 
participants who are age 18 can be provided a ride share through NIDA or reimbursed for their 
travel expenses, or given a $15 flat rate. Unaccompanied minors may be reimbursed for travel 
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Meals or snacks will be provided during study visits.
Method of Payment: The NIDA IRP has a contractor in place for remuneration. The 
participant/parent/guardian will generally receive payment earned for that day at the end of each 
day of participation when possible. If any procedures are completed remotely or during evening 
or weekend hours, payment may be delayed. 
Remuneration will generally be in cash payments. Payment by gift cards (as long as NIDA IRP 
guidelines permit), check or electronic means (e.g., via PayPal) may also be offered. NIDA IRP 
has a cash limit per day so the participant/parent/guardian may choose multiple payment methods 
if they are owed more than the current limit, in one visit. We will coordinate getting any payments 
due to the participant during regular business hours with the various payment options described 
above.  Payment by check or electronic means (e.g., via PayPal) may also be offered.  
6
STUDY INTERVENTION
6.1
Study Interventions(s) or Experimental Manipulations(s) Administration
6.2
Study Intervention or Experimental Manipulation Description
Description of intervention: MBSR Program:  The adapted MBSR program is a structured 
evidence-based 9-week program that consists of eight weekly 2-hour sessions and one 3-hour 
retreat. We will conduct 4-6 MBSR groups of 8-12 participants each.  The program content 
includes: 1) material related to mindfulness, meditation, yoga, and the mind-body connection; 2) 
experiential practice of mindful meditation (sitting, lying down, walking, etc.), mindful yoga, and 
“body scan”, and encouragement of home practice; and 3) group discussion of barriers to effective 
practice. MBSR group discussions are focused on issues related to the practice of mindfulness in 
daily life. As with our previous studies, the group will be led by an instructor trained in MBSR, 
experienced with mindfulness instruction in youth with psychiatric conditions, using the adapted 
MBSR workbook.  MBSR program fidelity will be tracked using a previously developed checklist 
consisting of the main concepts, content, activities, and qualitative assessment for each class. 
6.3
Administration  
The MBSR intervention will be delivered in-person or virtually for 9 weeks. Virtual MBSR 
sessions will be held via videoconference using an NIH Information Systems Security Officer 
(ISSO) approved teleconference software.
6.4
Fidelity
6.5
Interventionist Training and Tracking
A commercially available MBSR trainer, experienced in working with adolescents in research 
studies, will deliver the training. Documentation of the conduct of each training session will be 
provided. 
6.6
Measures to Minimize Bias: Randomization and Blinding
N/A
6.7
Study Intervention/Experimental Manipulation Adherence

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The trainer(s) will follow a manual in delivering the treatment and document the conduct of each 
session for review.
6.8
Concomitant Therapy
Participants may use their normal medications, including over-the-counter medications and dietary 
supplements, and prescribed medications. Medication usage will be assessed at each study visit 
and documented in the relevant Case Report Form (CRF).
6.9
Rescue Therapy 
N/A
7
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1
Discontinuation of Study Intervention/Experimental Manipulation
Participants who engage at any level in the MBSR training and are not disruptive will be allowed 
to continue with the intervention and the protocol in general. Only those who express a desire to 
withdraw from the MBSR, persist in disruptive behaviors during sessions, or are lost to follow-up 
with be discharged from the study. There are no safety endpoints that need follow-up after 
discontinuation of MBSR or the study. 
7.2
Participant Discontinuation/Withdrawal from the Study
Participants are free to withdraw from participation in the study at any time upon request.
An investigator may discontinue a participant from the study for the following reasons:
•
Continual non-compliance (e.g., repeatedly fails to show for scheduled protocol visit 
(excluding MBSR training sessions) without calling to reschedule, does not complete 
procedures as instructed, persistent disruptive behavior during MBSR training sessions, 
etc.)
•
Lost-to-follow-up; unable to contact subject (see Section 7.3, Lost to Follow-Up).
•
Any event or medical condition or situation occurs such that continued collection of follow-
up study data would not be in the best interest of the participant or might require an 
additional treatment that would confound the interpretation of the study.
•
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation.
•
Screen failure
•
The individual no longer wishes to participate.
The reason for participant discontinuation or withdrawal from the study will be documented in the 
participant’s electronic research record.
7.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she fails to return for MBSR intervention 
sessions, or any scheduled protocol visit and is unable to be contacted by the study staff. 

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The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:
•
Study staff will attempt to contact the participant and reschedule a missed follow-up visit 
within 2 weeks.
•
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record or study file. 
•
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.
8
STUDY ASSESSMENTS AND PROCEDURES
8.1
Screening Procedures
8.1.1
Screening activities performed prior to obtaining informed consent
A phone screen or online screener (see attached Phone Screen and Online Screening Survey) will 
be completed with the potential participant to preliminarily ascertain suitability for the study. 
Screening questions will cover participants’ clinical history, which comprises current substance 
use, including nicotine vaping, contraindications to MRI scanning, general health and mental 
health, including all regular medications, access to a smartphone and ability to participate in 
weekly MBSR training sessions (vaping group only). A waiver of consent is requested for the 
online screening survey and phone screen – please see section 10.
8.1.2 Screening activities performed after a consent for screening has been signed
At the first visit, after consent/assent is obtained, the following measures will be gathered to further 
assess eligibility for the study:
Diagnostic Assessment (~1.5 hours)
a.
Clinical history – clinician review
b. Mini International Neuropsychiatric Interview for Children and Adolescents-DSM-5.0 
version (MINI-KID-5) or SCID-RV
c.
MRI Safety Assessment
a.
Substance Use History
o
General Substance Use History Questionnaire (with tobacco & e-cigarette 
smoking, alcohol, and cannabis questions included)
o
Cannabis Use Disorder Test (CUDIT, 8 items, ~1-2 min)
8.2
Study Evaluations & Procedures after eligibility has been determined.
Administration of questionnaires, interviews, or other instruments (Table 1).

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The consent, screening activities listed in 8.1.2, and the baseline assessments listed below may be 
completed in the same visit virtually or in-person, and all or some of these procedures may also be 
completed in the same visit as the first scan session. Some questionnaires may be completed 
virtually in between the consent appointment and Scan Day 1.
Orientation and Initial Baseline Assessments (Visit(s) 1, may be conducted virtually) (~35-
55 min):
Demographics and Puberty (~2-5min)
a.
Demographics questionnaire
b. Pubertal Development Scale
Substance Use Measures
a.
General Substance Use (all participants)
o
Timeline Follow-back (TLFB)
▪
Past 28-days tobacco vaping (vaping days and vapes or puffs/day), tobacco 
smoking, cannabis, alcohol, other drugs if relevant. 7-day TLFB for later 
visits for vaping teens.
o
Craving Questionnaire (~1-5 min)
b. E-Cigarette Measures (Vapers only)
o
E-cigarette Dependence Scale (EDS, 4 items, 1 min)
o
Nicotine Social Influence Questionnaire (NSIQ, 1 min)
▪
Social influence - peer and family e-cigarette use and approval
o
Modified E-Cigarette Fagerstrom Test for Nicotine Dependence (FTND, 8 items, 
1-2 min)
Psychological Measures
o
Sensitivity to Reward and Sensitivity to Punishment Questionnaire (SRSPQ, 48 items, 
5 min)
o
Patient Health Questionnaire-9 (PHQ-9, 9 items, 2 min)
▪
Assesses degree of depression severity
o
General Anxiety Disorder-7 (GAD-7, 7 items, 2 min)
o
Difficulty in Emotion Regulation Scale (36 items, 4 min)
o
5-trial Adjusting Delay Discounting Task (bench, 2 min)
▪
Assesses discounting of future rewards compared to current rewards
o
Momentary Impulsivity Scale (4 items, 1 min)
Mindfulness Measures
o
Five-Facet Mindfulness Questionnaire (FFMQ, 39 items, 3 min)
Cognitive Measures
o
Digit Span Assessment (forwards and backwards) (DGS, ~3-5 min)
MBSR

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The study intervention, given to vaping teens, is a Mindfulness-Based Stress Reduction (MBSR) 
training. The intervention is a group-based instructor-led mindfulness-based stress reduction 
(MBSR) training. See section 4 for details related to MBSR training.
MRI Sessions (~2 hours):
Radiographic or other imaging assessments (Visits 1 and 11 for vaping participants; Visit 1 
only for controls)
MRI Data Acquisition
The study may use the 3T MRI with custom pulse sequences and image reconstruction and analysis 
software (via CRADA with Siemens using sequences developed at various universities). All 
sequences are within FDA approved specific absorption radiation (SAR) limits. We believe this 
study is a non-significant risk (NSR) device study subject to the abbreviated IDE requirements of 
21 CFR 812.2(b). The devices (custom pulse sequences and image reconstruction and analysis 
software), as used in this study, do not meet the definition of a significant risk (SR) device per 21 
CFR 812.3(m) because:
1.       It is not intended as an implant and presenting a potential for serious risk to the health, safety, 
or welfare of a subject because the MRI is not an implant.
2.       It will not be used in supporting or sustaining human life and does not present a potential 
for serious risk to the health, safety, or welfare of a subject because MRI will not be used in 
supporting or sustaining human life. 
3.       It will not be for a use of substantial importance in diagnosing, curing, mitigating, or treating 
disease, or otherwise preventing impairment of human health and presenting a potential for serious 
risk to the health, safety, or welfare of a subject because the MRI results will not be used to provide 
clinically relevant information for participants. 
4.       It does not otherwise present a potential for serious risk to the health, safety, or welfare of a 
subject because the pulse sequences and image reconstruction and analysis software are used 
within the FDA approved SAR limits.
Per regulations, abbreviated IDEs (NSR device studies) do not require an application to the FDA 
as the IRB acts as FDA’s surrogate for review, approval, and continuing review of these type of 
device studies.
At scan visits:
-
Participants will present to the NIDA-IRP BRC for a medical update, and an MRI safety 
screen, conducted by the MAI/designee or research nurse. They will also complete a 
nursing evaluation (weight, urine drug test, urine pregnancy test, urine cotinine test, breath 
CO, and ALC test), and will orient to the MRI scanner. Participants will then undergo a 
~60 min MRI session on a Siemens 3.0T MRI scanner using a 32-channel head coil. 
-
Participants will be instructed to abstain from cannabis, alcohol, and other drugs for 24 
hours and limit caffeine for 12 hours prior to scan visits. They will be instructed to continue 

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nicotine products as usual. Abstinence will be verified on scan days via self-report, and 
UDT (listed above), with participants rescheduled if they test positive for drugs on UDT 
and have signs of acute intoxication (per clinical assessment).  
-
Scan sessions will include: (1) anatomical MRI for registration (T1W), (2) resting-state 
scan (whole-brain T2*w gradient-echo EPI sequence) [10 minutes, eyes-open, fixation 
cross], (3) Diffusion Tensor Imaging (DTI).
Follow-up Assessments
Within three weeks of the MBSR training completion, vaping participants will complete substance 
use questionnaires, psychological assessments, mindfulness measures, and cognitive assessments 
in-person or via secure video call. Our goal is to complete both scan 2 and the initial post-MBSR 
training assessments within about 1 week after MBSR training. This first follow up visit may be 
combined with the post MBSR scan 2 but scan 2 may take place as late as approximately 6 weeks 
after MBSR training to accommodate scheduling. Participants will then have three more follow-
up visits, approximately a month apart, in which they complete the measures listed above. These 
three monthly visits will be dated from the completion of the first assessments following MBSR 
training (not the scan 2 date). Note: The Digit Span will only be completed at one of the follow up 
visits, and the FFMQ, DERS and SRSPQ will be completed during two of the visits, preferably 
the first and the last. The Delayed Discounting questionnaire will only be completed if the follow 
up visit is in-person. A nursing evaluation consisting of urine sample for a drug test, and breath 
CO and alcohol test will be taken at each in-person follow-up.
Participants will also engage with the Craving-to-Quit app to elucidate changes in vaping behavior, 
emotion, and cognition in the 3 months following the MBSR training. The follow-up visits will 
take about 1 hour each to complete. 
8.2.1 Biospecimen Evaluations
The following biospecimen tests will be collected at scan 1 (Visit 1), scan 2 (Visit 11), and follow-
up visits (12-15) to measure nicotine, THC, alcohol, and other drug use.
o
Urine Cotinine Test, Urine Drug Test (UDT)
o
Breath CO and ALC test
Urine samples acquired for measurements of pregnancy and drug usage at each visit will be 
destroyed once valid assays have been obtained.
8.2.2 Samples for Genetic/Genomic Analysis
N/A
8.2.2.1 Description of the scope of genetic/genomic analysis
8.2.2.2 Description of how privacy and confidentiality of medical information/biological 
specimens will be maximized
8.2.2.3 Management of Results
8.2.2.4 Return of Secondary Genomic Research Results

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8.2.2.5 Genetic counseling
N/A
8.3
Safety Assessments
Pre-scan assessments:
•
Medical update (e.g., height, weight, change in previously provided history, etc.)
•
MRI Safety Screen
•
Pregnancy test (females of childbearing potential)
Post-scan assessments:
•
 Assess for wellbeing 
No results will be discussed with participants unless something requires referral for medical 
follow-up.
Safety monitoring: At each scan visit to NIDA, participants are queried about their general 
medical and emotional health (including current medications and drug use history) since their last 
visit to NIDA and are observed throughout each visit at NIDA by study investigators. Any change 
in health status is noted by protocol staff and evaluated for relevance to the participant’s 
participation. Study staff will communicate with participants during the scan and any who want to 
terminate the scan for any reason will be allowed to. Investigators will refer the participant to the 
MAI for any medical adverse events or questions about recent medical conditions.
8.4
Adverse Events and Serious Adverse Events
8.4.1
Definition of Adverse Event
Consistent with the Common Terminology Criteria for Adverse Events (CTCAE), an adverse 
event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medical treatment or procedure that 
may or may not be considered related to the medical treatment or procedure. Severity of each AE 
(grading) will be determined consistent with the Common Terminology Criteria for Adverse 
Events (CTCAE) version 5.0.
8.4.2
Definition of Serious Adverse Events (SAE)
A Serious Adverse Event is any Adverse Event that:
•
Results in death;
•
Is life-threatening (places the subject at immediate risk of death from the event as it 
occurred);
•
Results in inpatient hospitalization or prolongation of existing hospitalization;
•
Results in a persistent or significant disability/incapacity;
•
Results in a congenital anomaly/birth defect; OR
•
Based upon appropriate medical judgment, may jeopardize the subject’s health and may 
require medical or surgical intervention to prevent one of the other outcomes listed above 
in this definition (examples of such events include allergic bronchospasm requiring 
intensive treatment in the emergency room or at home, blood dyscrasias or convulsions 

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that do not result in inpatient hospitalization, or the development of drug dependency or 
drug abuse).
An adverse event (AE) or suspected adverse reaction is considered “serious” if, in the view of 
either the investigator or sponsor, it results in any of the following outcomes: death, a life-
threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or a congenital anomaly/birth defect. Important medical events that may not result in 
death, be life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse.
8.4.3
Classification of an Adverse Event
8.4.3.1 Severity of Event
Severity of each AE (grading) will be determined consistent with the Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0.
Grade 1 Mild; asymptomatic or mild symptoms, or clinical or diagnostic observations only, or 
intervention not indicated.
Grade 2 Moderate; minimal, local or noninvasive intervention indicated, or limiting age-
appropriate instrumental ADL.
Grade 3 Severe or medically significant but not immediately life-threatening, or hospitalization 
or prolongation of hospitalization indicated, or disabling, or limiting self-care ADL.
Grade 4 Life-threatening consequences, or urgent intervention indicated.
Grade 5 Death related to AE.
8.4.3.2 Relationship to Study Intervention/Experimental Manipulation
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study procedures administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study procedures should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive.
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within 
a reasonable time after administration of the study procedures, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal. 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of study procedures). However, other 

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factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate.
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study procedures administration makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after administration of the study procedures) 
and in which other drugs or chemicals or underlying disease provides plausible explanations (e.g., 
the participant’s clinical condition, other concomitant treatments).
Not Related – The AE is completely independent of study procedures administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an alternative, 
definitive etiology documented by the clinician.
8.4.3.3 Expectedness 
A clinician will be responsible for determining whether an adverse event (AE) is expected or 
unexpected. An AE will be considered unexpected if the nature, severity, or frequency of the event 
is not consistent with the risk information previously described for the study procedures.
8.4.4
Time Period and Frequency for Event Assessment and Follow-Up
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention 
of study personnel during study visits.
All AEs will be captured in the participant’s NIDA IRP electronic research record, which is 
currently, the Clinical Data Warehouse (CDW). Information to be collected includes event 
description, time of onset, clinician’s assessment of severity, relationship to study procedures 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study will be documented 
appropriately regardless of relationship. All AEs except those that are “Not Related” will be 
followed to adequate resolution/stabilization.
Any medical or psychiatric condition that is present at the time that the participant is screened will 
be considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE. 
The events in the table below are very often seen with MRI and therefore fully expected (similar 
to minor bleeding or bruising after blood draws or injections). They will not be recorded as AEs 
because their occurrence does not constitute information that would inform or change the 
established risk profiles of MRI. Events solely related to conditions present at baseline, will also 
not be recorded as AEs.
Conditions Commonly Associated with MRI and Not to be Recorded as AEs:
CTCAE Condition
CTCAE Grade
CTCAE Grade Description
General disorders: Fatigue
Grade 1
Fatigue relieved by rest

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Ear 
and 
labyrinth 
disorders: 
Tinnitus
Grade 1
Mild symptoms; intervention not 
indicated
Musculoskeletal and connective 
tissue disorders: Back pain
Grade 1
Mild pain
Nervous 
system 
disorders: 
Dizziness
Grade 1
Mild unsteadiness or sensation of 
movement
Nervous 
system 
disorders: 
Headache
Grade 1
Mild pain
8.4.5
Adverse Event Reporting  
In consultation with the PI, a trained member of the study team will be responsible for conducting 
an evaluation of all adverse events and shall report the results of such evaluation to the NIH 
Institutional Review Board (IRB) as per Policy 801.
The PI will report all unanticipated adverse device effects (UADEs) to the Sponsor within 10 
working days. This should be submitted to the ORSC RSS by a MedWatch Form (Form 3500A), 
which should be sent ENCRYPTED to the REGSupportORSC@nih.gov inbox with a cc to the 
CD/CMO/designee. The Sponsor will immediately conduct an evaluation to determine if the 
UADE presents unreasonable risk to subjects. If the Sponsor determines that the UADE presents 
unreasonable risk, part of the study presenting the risk or all of the study will be terminated within 
5 working days of the determination, and no later than 15 working days after the Sponsor received 
notice of the UADE. For non-significant risk device investigations terminated due to an UADE, a 
sponsor may not resume a terminated investigation without IRB and FDA approval. 
ALL AEs that are collected, as determined by the written protocol, should be tracked in the ORSC 
RSS’s template AE tracker or similar document. All AEs will be sent to the Sponsor quarterly, or 
at minimum annually.  
In addition, the PI will report to the Sponsor, within 5 working days, a withdrawal of approval by 
the reviewing IRB of the investigator’s part of an investigation. The Sponsor will notify the FDA 
of withdrawal of IRB approval.  
The PI will report to the Sponsor, within 5 working days, if the device is used without obtaining 
informed consent. The Sponsor will notify the FDA of use of the device without informed consent.
8.4.6
Serious Adverse Event Reporting  
In consultation with the PI, a trained member of the study team will be responsible for conducting 
an evaluation of a serious adverse event and shall report the results of such evaluation to the 
Sponsor and the NIH Institutional Review Board (IRB) as per Policy 801.

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8.4.7
Events of Special Interest  
N/A
8.4.8
Reporting of Pregnancy  
A urine pregnancy test will be included in the screening and before each MRI scan. If a participant 
is pregnant, we will talk to them about their health and options. If the study team is concerned that 
the participant may not get health care they need, we will discuss the pregnancy with the 
consenting parent/guardian even if the participant does not want us to. The participant may not 
participate in this study if she is pregnant.
8.5
Unanticipated Problems
8.5.1
Definition of Unanticipated Problems (UP)
Any incident, experience, or outcome that meets all of the following criteria:
•
Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review Board 
(IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; and
•
Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been caused 
by the procedures involved in the research); and
•
Suggests that the research places participants or others (which many include research staff, 
family members or other individuals not directly participating in the research) at a greater 
risk of harm (including physical, psychological, economic, or social harm) than was 
previously known or expected.
8.5.2
Unanticipated Problem Reporting
 The investigator will report unanticipated problems (UPs) to the NIH Institutional Review Board 
(IRB) as per Policy 801.
9
STATISTICAL CONSIDERATIONS
9.1
Statistical Hypothesis
•
Primary Endpoint(s): 
(1) Our central hypothesis is that frequent nicotine vaping in adolescents will be associated 
with impaired hippocampal connectivity (measured via s-rsFC) with large-scale brain 
networks (ECN, DMN, SN) involved in cognitive control and emotion regulation and 
differences in time in state and state transitions (measured via d-rsFC) between. 
Alternatively, our null hypothesis is that there will be no difference in the hippocampal 
connectivity or d-rsFC measures between groups (daily nicotine vaping adolescents and 
TD age-matched adolescents who do not vape).
(2) We hypothesize that the MBSR intervention will increase hippocampal connectivity to the 
ECN and normalize time in state and state transition measures in vaping adolescents, with 

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Abbreviated Title: Mindfulness and Teen Vaping
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these ΔrsFC predicting Δvaping behaviors. Alternatively, our null hypothesis is that there 
will be no change in rsFC or vaping behaviors as a result of the MBSR intervention. 
•
Secondary Endpoint(s):
(1) Descriptive statistics will be calculated to determine the feasibility and acceptability of 
technology-delivered MBSR, while preliminary efficacy to reduce vaping in adolescents 
will be assessed with t-tests.
9.2
Sample Size Determination
General fMRI power. Since fMRI is the main outcome measurement utilized in the present 
protocol, the key power analysis pertains to the fMRI data. However, prospective power analyses 
for fMRI data are complicated for several reasons. First, fMRI data are analyzed in a hierarchal 
manner such that both the intra-participant variance from the time-course data and the inter-
participant variance across individuals could affect statistical power. A large number of time points 
tend to mitigate effects of intra-participant variance, but temporal autocorrelation and scanner 
limitations limit the number of independent measurements per unit time and thus the number of 
independent time points that are collected. In addition, effect sizes and both types of variance will 
vary spatially. Because of this, a given study may have sufficient power to detect differences in 
some brain regions, but lack sufficient power in other regions where the null hypothesis is false. 
Finally, fMRI analysis consists of a very large number of non-independent multiple comparisons, 
greater than 1.5 million at the group level, necessitating correction methods less severe than a 
Bonferroni correction, as discussed above. Thus, a proper power analysis on fMRI data requires 
simulating all of these effects. Desmond and Glover97 have performed such a simulation. They 
show for a relatively modest signal change of 0.5% during a cognitive task and with an intra-
participant standard deviation of 0.75% and an inter-participant standard deviation of 0.5%, that 
11 participants are required for a power of 0.8 using p < 0.05. Using a false positive rate of p < 
0.002, a level more consistent with a cluster size threshold to correct for multiple comparisons98, 
and with the variances kept the same, approximately 21 participants are needed for an expected 
signal change of 0.5% and 11 participants for a signal change of 0.75%. For more than ~100 
independent time points, power (and hence the intra-participant variance) is relatively independent 
of the number of time points97. As signal change is often less than .5% in fMRI studies, we aim to 
recruit 40 teen vapers and 40 matched control teens for this study. 
9.3
Populations for Analyses
•
Modified Intention-to-Treat Analysis Dataset: All frequent nicotine vaping participants 
approved to participate in the MBSR intervention who complete the first scan day will be 
included in the comparison of vaping to non-vaping teens. Non-vaping teens who complete 
the scan will be included in this analysis.
Frequent nicotine vaping participants who completed the study intervention (regardless of 
number of sessions actually attended) and complete both MRI scans will be included in the 
pre-post imaging comparison in the vaping group. If they also complete at least one follow-
up visit, they will be included in the assessment of effect of MBSR on vaping and related 
outcome measures.  
9.4
Statistical Analyses
9.4.1
General Approach

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Quantitative analysis:  For quantitative analysis of behavioral variables assessed at multiple time 
points, changes in scores across time will be presented descriptively (means, SDs) and analytically.  
Behavioral data encompasses scores on questionnaires assessing substance use variables, 
psychological functioning, and mindfulness processes. Paired t-tests will be used to examine pre- 
to post-treatment changes in continuous measures, and chi-squares will be used to test for pre- to 
post-treatment changes in categorical variables. Regression will be used to assess continuous 
relationships between scores on behavioral performance measures, self-report questionnaires, 
neuroimaging data (both pre-treatment and change from pre- to post-treatment), and outcome data. 
fMRI data: resting time courses averaged from seeds of hippocampal subregions will be extracted 
and correlated with time courses from all other voxels in the brain on an individual level. Individual 
maps will be combined to obtain group level maps of connectivity from hippocampal subregions 
which will be compared between groups at baseline and within group pre- vs post-MBSR with t-
tests. 
9.4.2
Analysis of the Primary Endpoints
Behavioral data analysis: Group differences (Vaping vs. TD) will be evaluated via chi-squares, 
independent t-tests (Primary Endpoint 1).  In addition to EOT nicotine abstinence, Δscores will be 
calculated for each behavioral measure (e.g. vaping frequency, emotion regulation) and will be 
used for within-subject analyses to characterize MBSR-related behavioral change (Primary 
Endpoint 2).  
rsFC fMRI data analysis:  Seed-based ROI whole-brain rsFC analyses between a priori defined 
hippocampal seed regions and large-scale brain networks (focusing on DMN, ECN, SN). Whole-
brain regression analyses will be conducted for each seed on each individual’s preprocessed data 
resulting in a Fisher-transformed z-value in each brain voxel (DV).  Seed regions: Right- and left- 
whole and sub-region hippocampal ROI seeds such as those defined via probabilistic voxel maps 
created by Chase et al.99 will be used for rsFC analyses.  Target network identification:  
Hypothesis-driven seed-based analyses will be constrained to voxels within each of three 
functionally generated masks of large-scale brain networks (DMN, ECN, SN) identified via group 
independent component analysis6 or taken from a published atlas. 
s-rsFC Analysis:  Independent and Paired t tests will examine group (Vaping vs. TD) (Primary 
Endpoint 1) and session (Pre/Post-MBSR) (Primary Endpoint 2) effects in s-rsFC strength between 
each hippocampal seed and voxels within each of the 3 network masks (e.g., seed-ECN voxels). 
 d-rsFC Analysis:  d-rsFC will be estimated using a sliding window method21,22 creating 
windowed correlation matrices, to which a k-means clustering algorithm will be applied to identify 
states.6 Independent and Paired t-tests will examine group (Vaping vs. TD) (Primary Endpoint 1) 
and session (Pre vs. Post-MBSR) (Primary Endpoint 2) differences in d-rsFC DVs: state 
occupancy and transitions. 
Correlational analyses:  To test relationships between MBSR-related ΔrsFC and Δ vaping 
behaviors and other behavioral outcomes, we will use regression analyses.  
Post-hoc analyses:  Post-hoc ROI seed-based whole-brain connectivity analyses will test if the 
regions showing mindfulness-related ΔrsFC are distinct from or overlap with regions modulated 
by nicotine exposure (from Primary Endpoint 1).

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9.4.3
Analysis of the Secondary Endpoint(s)
Our secondary endpoint aims to determine the feasibility and acceptability of the MBSR 
intervention and thus we will collect descriptive data to determine the feasibility and acceptability 
via program engagement. To assess program engagement: the # of MBSR group sessions attended 
will be calculated for each participant and the # and proportion of participants completing 50%, 
75%, and 100% of group sessions will be calculated.
To assess preliminary efficacy, we will use the data as described for Primary Endpoint 2. Primary 
and secondary outcomes for the clinical trial are shown below.
9.4.4
Safety Analyses
Outcome Type
Measures 
Used 
for 
Outcome
Definition of Outcome
Primary Efficacy 
Outcomes
TLFB, Urine Cotinine Test
The primary outcome measure is change in 
vaping frequency at the post-MBSR follow-
up MRI session.   
Primary Group Effect 
Outcome
FFMQ mindfulness scale, 
Difficulties 
in 
emotion 
regulation 
scale 
(DERS), 
General 
Substance 
Use 
History Questionnaire, Digit 
Span assessment
The primary outcome measure for the vaping 
vs TD group comparison will be the substance 
use, mental health and cognitive function 
measures at baseline.
Secondary Efficacy 
Outcomes
TLFB, FFMQ mindfulness 
scale, Difficulties in emotion 
regulation 
scale 
(DERS), 
Digit Span assessment
Secondary efficacy outcomes are changes in 
craving, mindfulness, negative emotions 
(depression, anxiety), emotion regulation and 
cognitive measures from baseline to post-
MBSR study visit.
Primary 
Feasibility/Acceptability 
Outcomes
Recruitment, retention, 
program engagement, app 
use data 
MT intervention will be considered 
acceptable and feasible for use in this 
population if at least 75% of participants are 
retained through the EOT, and at least 75% 
of participants download the C2Q app and 
complete 1 module.  
Secondary 
Feasibility/Acceptability 
Outcomes
Participant 
self-report 
on 
MBSR program and CTQ 
utility, ease of use, etc. 
Secondary outcomes for 
feasibility/acceptability are self-report 
responses about the helpfulness and utility of 
the MBSR program and C2Q app.

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N/A – This study does not involve any intervention presenting significant risk to participants.
9.4.5
Baseline Descriptive Statistics
Tobacco vaping and other drug use measures:  Tobacco vaping/e-cigarette use (vaping days, 
vapes/vaping day) and other drug use in the past 28 days will be collected via TLFB at baseline 
and post-MBSR MRI follow-up visit. Additional information on time to first vape, nicotine 
concentration used, vape device used, use of flavors, social influence will be collected along with 
validated instruments measuring e-cigarette dependence (EDS).
Biochemical measures of drug use: Semi-quantitative urine cotinine testing and carbon monoxide 
(CO) monitoring will be used to verify self-reported post-MBSR abstinence. Urine drug testing, 
and breath alcohol level will be collected.
Other self-report assessments: Self-report measures of mood, anxiety, coping, emotion regulation, 
cognitive function and mindfulness found to show changes following MT in prior studies will be 
collected and used in theory-driven exploratory analyses.
9.4.6
Planned Interim Analyses
This is a small pilot study. We may conduct an analysis to allow our trainees to submit an abstract 
for internal NIH or other scientific meetings. Such analyses will not be used to alter the protocol.
9.4.7
Sub-Group Analyses
In this small pilot study, it is unlikely that we will be able to conduct subgroup analyses, however, 
if there are sufficient numbers, age, sex, race and SES will be considered for subgroup analyses.  
9.4.8
Tabulation of individual Participant Data
Individual participant data will be listed by measure and timepoint. 
9.4.9
Exploratory Analyses
Whole brain connectivity with alternative seeds relevant to mediation and nicotine dependence 
such as dorsal anterior cingulate will be carried out similar to the hippocampal seed analyses 
described above. Graph theory metrics may be calculated on whole brain connectivity measures. 
10 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS
10.1 Informed Consent Process
10.1.1 Consent/Assent Procedures and Documentation
Prior to the first visit, permission to conduct a brief phone screen or online screen will be obtained 
from the participant (see attached Phone Screen and Online Screening Survey and section 8). 
Participant permission for the brief phone screen and online screen will be documented within the 
respective forms (in REDCap). We request a waiver of participant and parental consent for the 
phone and online screening:

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•
The phone and online screen questions present no more than minimal risk of harm to 
subjects and involves no procedures for which written consent is normally required outside 
of the research context. 
•
The waiver or alteration will not adversely affect the rights and welfare of the subjects.
•
The clinical investigation could not practicably be carried out without the waiver (it would 
be impractical and burdensome for subjects to undergo full consent process for a brief pre-
screening).
•
Subjects will be provided with additional pertinent information if they proceed to study 
enrollment.
If the pre-screen does not lead to clear disqualification from study participation, participants will 
be invited to participate in the study. Written informed assent/consent will be obtained from each 
participant and their parent/guardian, respectively (if the participant is a minor). Both the minor 
and parent/legal guardian are required to sign the consent document after they are presented with 
the study details, before taking part in study procedures (with the exception of those listed in 
Section 8.1.2). In situations where there is joint custody of a child, both parents must give 
permission for their child to participate. Both parents must sign the consent form. The other 
parent’s permission can be obtained via telephone or an NIH approved remote platform and 
documented in the NIDA IRP electronic research record. If one parent/guardian is remote, the 
informed assent/consent document will be sent to the parent/guardian. An explanation of the study 
will be provided over the telephone after the parent/guardian has had the opportunity to read the 
document. The parent/guardian and child will sign and date the informed assent/consent. The 
signed informed assent/consent document will be sent back to the consenting investigator who will 
sign and date the form with the date the consent was returned. A fully executed copy will be 
returned to the participant. The informed assent/consent process will be documented in the NIDA 
IRP electronic research record. The minor’s right to dissent from participation or withdrawal from 
this study will be honored. Written assent of the minor and written consent of the parent/guardian 
will be obtained on the same consent document. If the participant is 18 at enrollment, written 
consent will be obtained and no parental consent is required.  
The informed consent document will be provided as a physical or electronic document to the 
participant (and parent/guardian of minors as applicable) for review prior to consenting/assenting. 
A designated study investigator will carefully explain the procedures and tests involved in this 
study, and the associated risks, discomfort and benefits in age-appropriate language. In order to 
minimize potential coercion, as much time as is needed to review the document will be given, 
including an opportunity to discuss it with friends, family members and/or other advisors as 
applicable, and to ask questions of any designated study investigator. 
The initial consent/assent process as well as re-consent/re-assent, when required, may take place 
in person or remotely (e.g., via telephone or other NIH approved remote platforms used in 
compliance with policy, including HRPP Policy 303) per the discretion of the designated study 
investigator and with the agreement of the participant and parent/guardian for minors. Whether in 
person or remote, the privacy of the subject will be maintained. Consenting investigators (and 
participant/parent, when in person) will be located in a private area (e.g., study room). When 
consent/assent is conducted remotely, the participant and parent/guardian will be informed of the 
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needed. Whether the consent/assent process is in-person or remote, participants and investigators 
may view individual copies of the approved consent document or the same copy (e.g., the 
investigator may share their screen with the participant/parent onsite or remotely). 
Once the subject and parent/ guardian for minors verbally demonstrate understanding to the 
investigator and agrees to the process, a quiz evaluating understanding of study procedures is 
administered. Provided the participant and parent/guardian scores at least 80% correct, the 
participant (and parent/guardian for minors) is invited to sign the consent document. If the score 
on the quiz is less than 80% correct, the investigator will review the quiz results and clarify 
incorrect answers, then re-administer the quiz. Failure to obtain 80% correct score on the second 
administration of the quiz, which is exceedingly rare, eliminates the subject from participation in 
this study.  
A signed informed consent/assent, when applicable, will be obtained prior to any research 
activities taking place (with the exception of procedures listed in Section 8.1.2). Consent/assent 
will be documented with required signatures on the physical document (which includes the printout 
of an electronic document sent to the participant) or on the electronic document. Electronic 
signatures (i.e., the “signature” is digitally generated) will not be used. When a hand signature with 
a finger, stylus, mouse, or the like on an electronic document is used for the documentation of 
consent, this study will use one of the following electronic platforms to obtain the required 
signatures:
• Adobe Acrobat platform (which is not compliant with 21 CFR Part 11);
• Foxit (which is not compliant 21 CFR Part 11);
• DocuSign (which is not compliant 21 CFR Part 11); 
The parent/guardian and participant is provided a copy of the signed consent form for their own 
records. Enrollment is documented in the participant’s electronic research record.
10.1.2 Consent for minors when they reach the age of majority
When a pediatric subject reaches the age of majority, continued active participation (including 
ongoing interactions with the subject) will require that consent be obtained from the now adult 
with the standard protocol consent document to ensure legally effective informed consent has been 
obtained.
However, when we have no ongoing interactions with the subjects, including if subjects are lost to 
follow-up or withdrawn from the study, or have completed the study, we request a waiver of 
informed consent to continue to use data and/or specimens obtained from those individuals. 
Requirements for a Waiver of Consent consistent with 45 CFR 46.116 (f)(3):
(1) The research involves no more than minimal risk to the subjects.
a.
Analysis of samples and data from this study involves no additional risks to 
subjects.
(2) The research could not practicably be carried out without the waiver or alteration.
a.
Considering the length of time between the minor’s last contact with the 
research team and their age of majority, it could likely be very difficult to locate 

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them again. A significant reduction in the number of samples analyzed is likely 
to impact the quality of the research. 
(3) As the research involves using identifiable private information or identifiable 
biospecimens, the research could not practicably be carried out without using such 
information or biospecimens in an identifiable format. 
a.
Though the purpose of future studies cannot yet be known, they often involve 
the correlation of clinical outcomes and clinical interventions with laboratory 
studies.  Such information would be unavailable if access to medical record 
numbers was unavailable. 
(4) The waiver or alteration will not adversely affect the rights and welfare of the subjects.
a.
Retention of these samples or data does not affect the welfare of subjects. 
(5) There will be no pertinent information after initial participant to provide the the 
participants,
a.
We only request a waiver of consent for those subjects who have been lost to 
follow-up or withdrawn from the study, or have completed the study, prior to 
reaching the age of majority.
10.1.3 Considerations for Consent of NIH staff, or family members of study team members
If the potential participant is a member of the research team where this research is taking place, 
procedures outlined in NIH HRPP Policy 404 will be followed. Consent for NIH staff will be 
obtained as detailed above with the following additional protections:
Consent from staff members will be obtained by an individual independent of the staff member’s 
team whenever possible.  Otherwise, the consent procedure will be independently monitored by 
the CC Department of Bioethics Consultation Service to minimize the risk of undue pressure on 
the staff member.
10.1.4 Consent of Adults who lack, or lose, decision-making capacity to consent to research 
participation
Participants who are 18 and unable to consent to research are excluded from enrolling in the 
protocol. Participants who are under 18 and are unable to provide assent or cannot obtain consent 
from their parent/guardian are excluded from enrolling in the protocol. However, it is possible that 
subjects enrolled in the protocol may permanently lose the capacity to consent for themselves 
during the course of this study.  In the event this occurs, the subjects will be withdrawn from the 
study.  
10.2 Study Discontinuation and Closure
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigator, funding agency, and regulatory authorities.  If the study is prematurely terminated or 
suspended, the Principal Investigator (PI) will promptly inform study participants and 
parent/guardian (if applicable), the Institutional Review Board (IRB), and sponsor and will provide 

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the reason(s) for the termination or suspension.  Study participants and parent/guardian (if 
applicable) will be contacted, as applicable, and be informed of changes to study visit schedule.
 Circumstances that may warrant termination or suspension include, but are not limited to:
•
Determination of unexpected, significant, or unacceptable risk to participants
•
Insufficient compliance of study staff to the protocol requirements
•
Data that are not sufficiently complete and/or evaluable
•
Determination that the primary endpoint has been met
•
Determination of futility
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and, as applicable, the Food and Drug Administration 
(FDA), or other relevant regulatory or oversight bodies (OHRP, DSMB).
10.3 Confidentiality and Privacy
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff. This confidentiality is extended to cover testing of biological samples in addition to the 
clinical information relating to participants.  Participants will be assigned a code number without 
personally-identifying information following their first contact in the protocol. This number will 
be used throughout the experiment and will be the only identifier on specimen samples, behavioral 
and physiological archival data, fMRI/MRI data.  The identity of participants will not be revealed 
at scientific meetings, in publications or other vehicles of public communication. The PI and co-
investigators will have access to the ID code. Clinical research data and questionnaire data may be 
gathered in the CDW, a secure database on a closed network, or REDCap, a similarly secure 
system. Access to records in the CDW or REDCap is protected by a system of password-protected 
accounts and monitored by the Clinical Director (CD). Data downloaded from the CDW or 
REDCap for analysis will be used on NIH approved systems and applications. 
All research activities will be conducted in as private a setting as possible.
10.3.1 Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data 
Sharing Policies
It is NIH policy that the results and accomplishments of the activities that it funds should be made 
available to the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all 
mechanisms used to share data will include proper plans and safeguards for the protection of 
privacy, confidentiality, and security for data dissemination and reuse (e.g., all data will be 
thoroughly de-identified and will not be traceable to a specific study participant). Plans for 
archiving and long-term preservation of the data will be implemented, as appropriate. 
10.3.2 Certificate of Confidentiality
To further protect the privacy of study participants, the Secretary, Health and Human Services 
(HHS), has issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, 
behavioral, clinical or other human subjects research funded wholly or in part by the federal 
government.  Recipients of NIH funding for human subjects research are required to protect 
identifiable research information from forced disclosure per the terms of the NIH Policy (see 

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https://humansubjects.nih.gov/coc/index). As set forth in 45 CFR Part 75.303(a) and NIHGPS 
Chapter 8.3, recipients conducting NIH-supported research covered by this Policy are required to 
establish and maintain effective internal controls (e.g., policies and procedures) that provide 
reasonable assurance that the protocol is managed in compliance with Federal statutes,  and 
regulations. It is the NIH policy that investigators and others who have access to research records 
will not disclose identifying information except when the participant consents or in certain 
instances when federal, state, or local law or regulation requires disclosure. NIH expects 
investigators to inform research participants of the protections and the limits to protections 
provided by a Certificate issued by this Policy.
10.4 Storage, Use, and Sharing of Specimens and Data for Secondary Research
Data collected for this study will be stored on NIH approved systems and applications.
No biological samples will be stored.
 To advance science, it is helpful for researchers to share information.  We share information with 
researchers outside the NIH in two ways.  Most commonly, we have specific partnerships with 
other researchers.  Also, we may put data into one or more scientific databases, where it is stored 
along with information from other studies.  Researchers can then study the information combined 
from many studies to learn even more about health and disease.
We will share some protocol data with our scientific research partners inside or outside the NIH.  
Research partners outside the NIH sign an agreement with the NIH to share data.  This agreement 
indicates the type of data that can be shared and what can be done with those data.
Some information collected under this protocol may be placed into one or more scientific databases 
after it has been stripped of identifiers such as name, so that it may be used for future research on 
any topic and shared broadly for research purposes.  A researcher who wants to study the 
information must apply to the database and be approved.  Researchers with an approved study may 
be able to see and use the data from this protocol, along with that from many other studies.  We 
do not expect any direct benefits for participants resulting from the use of protocol data and 
information, though new discoveries that may help other people could occur.  The Principal 
Investigator is open to answering any participant questions about how these data may be used. 
The Neuroimaging Research Branch (NRB) collects data and human samples (henceforth simply 
referred to as data) in its protocols. Data analysis typically proceeds long after the data collection 
has ceased. This analysis includes that described in the protocol and novel analysis that were not 
anticipated or existing during the life of the protocol. As new methods become available, additional 
data analyses will be conducted utilizing new methods consistent with the aims of the project. 
Additionally, de-identified data may be shared with properly administered databases and/or with 
collaborators with whom proper data sharing agreements are in place, after consultation with and 
approval from the NIDA-IRP Scientific Director. Data shared with NIH investigators outside of 
NIDA, unless otherwise stated, would be sent by NIDA as de-identified data via secure email, 
encryption or secured ftp. The code to those data will not be shared. 
10.5 Safety Oversight

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The clinical research team will meet on a regular basis (approximately weekly) when subjects are 
being actively enrolled/evaluated on the study to discuss each subject.  
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Events meeting requirements for expedited reporting as described in HRPP 
Policy 801 will be submitted within the required timelines. 
The principal investigator will review all data on each subject to ensure safety and data accuracy. 
The principal investigator will personally conduct or supervise the investigation and provide 
appropriate delegation of responsibilities to other members of the research staff.
10.6 Clinical Monitoring
Clinical site monitoring is conducted to ensure that the rights and well-being of study participants 
are protected, that the reported study data are accurate, complete, and verifiable, and that the 
conduct of the study is in compliance with the currently approved protocol/amendment(s), with 
International Council for Harmonization Good Clinical Practice (ICH GCP), and with applicable 
regulatory requirement(s). 
The study investigators will be responsible for monitoring throughout the study and will verify 
data collection on an ongoing basis. 
Independent audits will be conducted by Intramural Research Program Auditing Committee 
(IRPAC) Coordinated by the Offices of the Clinical Director at NIAAA and NIDA.
10.7 Quality Assurance and Quality Control
Quality assurance (QA) and Quality control (QC) procedures will be monitored by the PI and 
research team. The PI will provide direct access to all study related source data/documents, and 
reports for the purpose of monitoring and auditing.
10.8 Data Handling and Record Keeping
10.8.1 Data Collection and Management Responsibilities
Data collection will be the responsibility of the clinical trial staff under the supervision of the 
principal investigator. The investigator will be responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported.
All source documents will be completed in a neat, legible manner to ensure accurate interpretation 
of data.  
Adverse events, clinical data and medical history information collected during screening and in 
this protocol is stored in the NIDA IRP electronic research record (CDW) or similar database, 
which is password protected and has limited access.
Any paper form of research records used by investigators will be kept in study-specific binders. 
These binders are kept in a locked cabinet, in a locked room, which has limited access. Binders 
remain in this room at all times, apart from when required for study sessions.  At the completion 
of each session the folder will be returned to the locked cabinet by the investigator or research 
associate responsible for the experimental session. Data (physiological, imaging, behavioral) 
obtained during experimental sessions is stored on password protected, network drives, which have 

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limited access.  Data stored on these drives is identified by study number, participant number 
and/or task.  No personal identifiers are stored with the data.
Electronic data collection forms will either be collected in CDW and/or another NIH approved 
secure application such as REDCap and stored securely. All data will be maintained and backed 
up in compliance with NIH and NIH IT policies.
10.8.2 Study Records Retention
Study documents will be retained per the NIH Intramural Records Retention Schedule. Data will 
be stored indefinitely.
10.9 Protocol Deviations and Non-Compliance
It is the responsibility of the investigator to use continuous vigilance to identify and report 
deviations and/or non-compliance to the NIH Institutional Review Board as per Policy 801.  All 
deviations must be addressed in study source documents, reported to the NIDA IRP Clinical 
Director. The investigator is responsible for knowing and adhering to the reviewing IRB 
requirements.
10.9.1.1 NIH Definition of Protocol Deviation
A protocol deviation is any changed, divergence, or departure from the IRB-approved research 
protocol. 
•
Major deviations: Deviations from the IRB approved protocol that have, or may have the 
potential to, negatively impact the rights, welfare or safety of the subject, or to substantially 
negatively impact the scientific integrity or validity of the study.
•
Minor deviations: Deviations that do not have the potential to negatively impact the rights, 
safety or welfare of subjects or others, or the scientific integrity or validity of the study.
10.10   Human Data Sharing, including Genomic Data Sharing, and Publication
10.10.1NIH Data Management and Sharing Policy and NIH Genomic Data Sharing Policy 
Compliance
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies 
to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated 
with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic 
data sharing. 
No genomic data will be collected for this study.
10.10.2 NIH Public Access Policy Compliance
This study will comply with the NIH Public Access Policy, which ensures that the public has 
access to the published results of NIH funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication.  
10.11   Collaborative Agreements  

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N/A
10.12   Agreement Type
N/A
10.13   Conflict of Interest Policy
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 
of this trial.  The study leadership in conjunction with the NIDA IRP has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest.
11 ABBREVIATIONS
AE
Adverse Event
ANCOVA
Analysis of Covariance
BOLD
Blood-Oxygen-Level-Dependent
CDW
Clinical Data Warehouse
CFR
Code of Federal Regulations
CLIA
Clinical Laboratory Improvement Amendments
CMP
Clinical Monitoring Plan
COC
Certificate of Confidentiality
CRF
Case Report Form
DHHS
Department of Health and Human Services
DMN
Default Mode Network
DSMB
Data Safety Monitoring Board
eCRF
Electronic Case Report Forms
ECN
Executive Control network
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GLP
Good Laboratory Practices
GMP
Good Manufacturing Practices
IB
Investigator’s Brochure
ICH
International Council for Harmonisation 
IDE
Investigational Device Exemption
IND
Investigational New Drug Application
IRB
Institutional Review Board
ISM
Independent Safety Monitor

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ISO
International Organization for Standardization
MBSR
Mindfulness Based Stress Reduction
MOP
Manual of Procedures
MRI
Magnetic Resonance Imaging
MSDS
Material Safety Data Sheet
MT
Mindfulness Training
NIH 
National Institutes of Health
NIH IC
NIH Institute or Center
OHRP
Office for Human Research Protections
PI
Principal Investigator
QA
Quality Assurance
QC
Quality Control
rsFC
resting state Functional Connectivity
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SN
Salience Network
SMC
Safety Monitoring Committee
SOA
Schedule of Activities
SOP
Standard Operating Procedure
UDT
Urine Drug Test
UP
Unanticipated Problem
US
United States
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