NIDA Phenotyping Assessments Battery (PhAB) Feasibility and Validation Study in Non-Intoxicated Drug Users
Conditions: Opioid-use Disorder, Cocaine Use Disorder, Marijuana Use Disorder, Healthy Controls
Sponsor: Virginia Commonwealth University

NIDA Phenotyping Battery  
Version 4, Date 06.12.19 
 
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NIDA Phenotyping Assessments Battery (PhAB) Feasibility and Validation Study in Non-
Intoxicated Drug Users. 
 
 
 
Principal Investigator:  Lori Keyser-Marcus, PhD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. LIST OF ABBREVIATIONS 
 
AE 
 
Adverse Event 

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ADHD  
Attention Deficit Hyperactivity Disorder 
ANT 
 
Attention Network Task 
BCBS  
Brief Substance Craving Scale 
ASRA  Adult Self-Report Symptom Checklist 
CARI  
Collaborative Advanced Research Imaging (VCU clinic) 
CSSR-S 
Columbia Suicide Severity Rating Scale 
CocUD Cocaine Use Disorder 
DSM-5 Diagnostic and Statistical Manual of Mental Disorders, Fifth Ed 
DTS 
 
Distress Tolerance Scale 
FTND  
Fagerstrom Test for Nicotine Dependence 
FTQ 
 
Family Tree Questionnaire 
HC 
 
Healthy Control 
IRB 
 
Institutional Review Board 
MAIA  
Multidimensional Assessment of Interoceptive Awareness 
MINI 
 
Mini International Neuropsychiatric Interview 
MCQ  
Metacognition Questionnaire 
MPQ-NEM 
Multidimensional Personality Questionnaire-Negative Emotional Temperament 
OUD  
Opioid Use Disorder 
PAB 
 
Phenotyping Assessment Battery 
PIB 
 
Platform Instrument Battery 
PANAS 
Positive and Negative Affect Schedule 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
PSQI  
Pittsburgh Quality of Sleep Index 
PTSD  
Post Traumatic Stress Disorder 
SAE 
 
Serious Adverse Event 
SST 
 
Stop Signal Task 
TAS-20 
Toronto Alexithymia Scale 
THC 
 
Tetrahydrocannabinol 
UPPS-P 
Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency 
VAS 
 
Visual Analog Scale 
VCU 
 
Virginia Commonwealth University 
WHO-DAS 
World Health Organization Disability Assessment Schedule 
WHO-QOL 
World Health Organization Quality of Life 
 
 
 
 
 
 
 
 
 
2. TABLE OF CONTENTS 
 
 
1. LIST OF ABBREVIATIONS 
………………………………………………………………………….2 
 
2. TABLE OF 
CONTENTS………………………………………………………………………………3 
 

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3. STUDY SYNOPSIS 
…………………………………………………………………………………..4 
 
4. BACKGROUND AND 
SIGNIFICANCE……………………………………………………………..5 
 
5. STUDY 
OBJECTIVES………………………………………………………………………………..6 
 
6. STUDY 
DESIGN………………………………………………………………………………………6 
6.1. Sample 
Size………………….………………………………………………………………………..6 
6.2. Study Schema and 
Timeline…………………………………………………………………………6 
6.3. Inclusion Criteria 
……………………………………………………………………………………...7 
6.4. Exclusion Criteria 
……………………………………………………………………………………..7 
 
7. STUDY 
PROCEDURES………………………………………………………………………………8 
7.1. Schedule of 
assessments……………………………………………….…………………………....8 
7.2. Subject Recruitment and 
Consenting……………………………………………………………….9 
7.3. Screening 
……………………………………………………………………………………………..10 
7.4. Phenotyping Assessment 
Visit……………………………………………………………………...11 
7.4.1. Assessment 
Measures…………………………………………………………………………11 
7.5. MRI Scan 
Visit…………………………………………………………………………………..15 
7.6. Participant 
Reimbursement………………………………………………………………………….16 
 
8. DATA MANAGEMENT PROCEDURES 
………………………………………………………………....16 
8.1. Data 
Collection………………………………………………………………………………………...1
6 
8.2. Data Entry and 
Validation…………………………………………………………………………….16 
8.3. Interim Analysis and Full Data 
Analysis……………………………………………………………..17 
 
9. SAFETY MONITORING AND 
REPORTING………………………………………………………………17 

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9.1. Subject 
Protection………………………………………………………………………………..17 
9.2. Adverse Event Monitoring and Reporting 
……………………………………………………..18 
9.3. Serious Adverse Event Monitoring and 
Reporting……………………………………………18 
9.4. Criteria for Participant Discontinuation from the 
Study……………………………………….19 
10.  INSTITUTIONAL REVIEW BOARD AND INDEPENDENT ETHICS 
COMMITTEE……………..19 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3. STUDY SYNOPSIS 
Title 
NIDA Phenotyping Battery Feasibility and Validation Study in Non-Intoxicated 
Drug Users 
 
Objective 
The primary objective of this project is to validate preliminary findings from the 
pilot study in order to refine the PhAB into a streamlined, validated deep 
phenotyping battery for addictions for adoption in future NIDA funded clinical 
trials. Specific aims to achieve this goal include: 
 
1. To finalize the PhAB battery content by examining levels of redundancy 
across PhAB measures, in order to further refine the assessment battery; 
2. To confirm percentages of participants that can complete the non-MRI 
portion of the protocol within two study visits; 
3. To assess whether PhAB battery profiles and performance measures vary in 
meaningful ways across substance use conditions, taking into account critical 
variables such as concomitant substance use, and psychosocial factors (e.g., 
trauma, depression, anxiety, etc); and 
4. To compare effective (directional) brain connectivity (via resting state fMRI 
and structural scans) between OUD, other relevant populations, and control 
participants and the relationship between effective brain connectivity and 
behavioral assessments from the PhAB  
 
Number of 
Subjects 
This project requires a final sample size of 400 subjects (100 non drug-using 
healthy control subjects, 50 subjects with primary stimulant use disorder, 200 
subjects with primary Opioid Use Disorder, and 50 subjects with primary 
Cannabis Use Disorder). 
Inclusion 
Criteria 
In order to participate in this study, subjects must: 
• 
Males and females between 18 and 70 years-of-age. 
• 
Current DSM-5 primary Substance Use Disorder:  Opioid, marijuana, 
stimulants (individuals with multiple types of substance use (e.g., 
opioid/marijuana will be included) 
• 
Have no contraindications for study participation as determined by 
medical history and concomitant medications. 
• 
Be able to demonstrate an understanding of study procedures and 
follow instructions including behavioral laboratory testing.  
• 
Be able and willing to comply with scheduled visits, and other study 
procedures. 
• 
Be able to read and complete forms and interviews in English. 
 
Inclusion Criteria  (Non-drug Using Healthy Controls) 
• 
Males and females between 18 and 70 years of age. 
• 
Have no contraindications for study participation as determined by 
medical history and concomitant medications. 
• 
Be able to demonstrate an understanding of study procedures and 
follow instructions including behavioral laboratory testing. 
• 
Be able and willing to comply with scheduled visits, and other study 
• 
Be able to read and complete forms and interviews in English. 
 
Exclusion 
General exclusion criteria: 

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Criteria 
• 
Current psychosis, mania, or suicidal/homicidal ideation 
• 
Meet current DSM-5 diagnosis of any psychoactive substance use 
disorder other than opioids,marijuana, stimulants, or nicotine. 
Diagnosis of mild to moderate use disorder for alcohol will not be 
considered exclusionary for any SUD group. 
• 
Have a history of seizures (excluding childhood febrile 
seizures), or loss of consciousness from traumatic injury for 
more than 30 minutes. 
• 
Have any other illness, or condition, which in the opinion of the PI or 
study physician would preclude safe and/or successful completion of 
the study. 
MRI exclusion criteria: 
• 
Metal fragments or implants, and/or history of fear of being in closed 
spaces for MRI scans. 
• 
Currently pregnant or nursing. 
 
Primary 
Outcome 
This study is a feasibility, construct and face validity study. The primary 
outcome measure is time taken to complete the battery, and rates of 
successful study completion.  
Duration 
1 year   
 
3. BACKGROUND AND SIGNIFICANCE 
 
There is profound heterogeneity of subjects in clinical studies of addictions, with patients being 
diagnosed by the primary substance of use. As a result, utilizing current DSM addictions 
classification leads to problems with signal detection and hamper the progress of the 
development of new drugs and treatments for substance use disorders (SUDs). Getting beyond 
the DSM-5 based definitions is necessary to “fingerprint” addiction phenotypes and 
endophenotypes, using machine-learning analyses of big data.  A detailed in-depth assessment 
of addiction phenotypes (deep phenotyping) may also include neuroimaging..   
 
In an effort to develop a “fingerprint” for addiction phenotypes, NIDA established a Workgroup to 
develop a phenotyping battery of tests and self-rated psychometric scales, supplemented by 
resting state fMRI to be administered to participants in any extramural clinical trial where 
addictions are assessed. The final phenotyping battery content was determined via consensus 
from both the selected experts- consultants group and the NIDA workgroup, and as such, the 
battery requires feasibility and validation study to finalize its content. The NIDA Phenotyping 
Assessment Battery (PhAB) covers six neurofunctional addiction domains :  Metacognition, 
Interoception, Cognition/Executive Function, Reward/Incentive Salience, Emotion/Negative 
Emotionality, and Sleep/Circadian Rhythm. The PhAB is meant to be administered during a 
Phenotyping visit - an extension of a screening visit in any clinical trial addictions protocol.   In 
addition to the PhAB, the group also developed an ancillary set of measures to be administered 
in conjunction with the PhAB in any addictions clinical trial during the Phenotyping visit.  The 
Platform Instruments include structured interviews, diagnostic measures (e.g., MINI), self report 
scales of symptom severity (e.g., ASRS-ADHD, VAS-Pain), trauma history (THQ), computer-
administered measures of intelligence (e.g., Shipley), and substance use measures (FTND, 
Timeline Follow-back), etc.  Clinical trial investigators would administer these scales and 
behavioral tasks   in addition to protocol nonspecific assessments (e.g., demographics) and 
medical evaluations (e.g, medical history and physical exams, genotyping, and labs) which 
could be done at Screening.   

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4. STUDY OBJECTIVES 
 
The primary objective of this project is to validate preliminary findings from the pilot study in 
order to refine the PhAB into a streamlined, validated deep phenotyping battery for addictions 
for adoption in future NIDA funded clinical trials. Specific aims to achieve this goal include: 
1. To finalize the PhAB battery content by examining levels of redundancy across PhAB 
measures, in order to further refine the assessment battery; 
2. To confirm percentages of participants that can complete the non-MRI portion of the protocol 
within two study visits; 
3. To assess whether PhAB battery profiles and performance measures vary in meaningful 
ways across substance use conditions, taking into account critical variables such as 
concomitant substance use, and 
psychosocial factors (e.g., trauma, depression, anxiety, etc); and 
4. To compare effective (directional) brain connectivity (via resting state fMRI and structural 
scans) between OUD, other relevant populations, and control participants and the relationship 
between effective brain connectivity and behavioral assessments from the PhAB  
 
 
5. STUDY DESIGN 
 
The study utilizes a four-group cross sectional cohort design.  A total of 400 participants (across 
4 cohorts) are targeted to complete the study) to include:  Healthy Controls (n=100), individuals 
with CocUD (n=50), individuals with OUD (n=200), and individuals with marijuana use disorder 
(n=50). The study is anticipated to take 1 year  to complete.  See Figure 1. 
 
 
 
 
a. Inclusion Criteria 
 

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Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
 
Inclusion Criteria (Individuals with SUDs) 
• 
Males and females between 18 and 70 years-of-age. 
• 
Current DSM-5 primary Substance Use Disorder:  Opioid, marijuana, stimulants 
(individuals with multiple types of substance use (e.g., opioid/marijuana will be 
included) 
• 
Have no contraindications for study participation as determined by medical history 
and concomitant medications. 
• 
Be able to demonstrate an understanding of study procedures and follow instructions 
including behavioral laboratory testing.  
• 
Be able and willing to comply with scheduled visits, and other study procedures. 
• 
Be able to read and complete forms and interviews in English. 
. 
Inclusion Criteria  (Non-drug Using Healthy Controls) 
• 
Males and females between 18 and 70 years of age. 
• 
Have no contraindications for study participation as determined by medical history and 
concomitant medications. 
• 
Be able to demonstrate an understanding of study procedures and follow instructions 
including behavioral laboratory testing. 
• 
Be able and willing to comply with scheduled visits, and other study 
• 
Be able to read and complete forms and interviews in English. 
 
 
b. Exclusion Criteria 
 
General Exclusion Criteria 
 
• 
Current psychosis, mania, or suicidal/homicidal ideation 
• 
Meet current DSM-5 diagnosis of any psychoactive substance use disorder other than 
opioids,marijuana, stimulants, or nicotine. Diagnosis of mild to moderate use disorder 
for alcohol will not be considered exclusionary for any SUD group. 
• 
Have a history of seizures (excluding childhood febrile seizures), or loss of 
consciousness from traumatic injury for more than 30 minutes. 
• 
Have any other illness, or condition, which in the opinion of the PI or study physician 
would preclude safe and/or successful completion of the study. 
 
MRI Exclusion Criteria 
 
• 
Metal fragments or implants, and/or history of fear of being in closed spaces for MRI 
scans. 
• 
Currently pregnant or nursing. 
 
 
6. STUDY PROCEDURES 
 
7.1 Time and Events Schedule  

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The time and events schedule is presented in Table 1 below.   
 
Table 1.  Schedule of Assessments 
 
Screening 
Assessment 
visit 
MRI visit 
Informed consent 
X 
 
 
Demographics 
X 
 
 
MINI-DSM5 
X 
 
 
C-SSRS 
X 
X 
X 
Medical survey 
X 
 
 
Prior/concomitant medications 
X 
X 
X 
Vital signs 
X 
X 
X 
Urine toxicology screen 
X 
X 
X 
* Physical exam  
X 
 
 
* Laboratory blood draw 
X 
 
 
* MRI contraindication and safety checklist 
X 
 
 
Pregnancy test (females) 
X 
X 
X 
Alcohol breathalyzer 
X 
X 
X 
Expired CO 
X 
X 
X 
Locator form 
X 
X 
X 
**Mock MRI scan 
X  
 
 
**Adult self-report symptom checklist (ASRA) 
X  
 
 
**Recent Life Events Questionnaire (Adults) 
X  
 
 
Timeline Follow-Back, Drug, Alcohol & Tobacco 
 
X 
 
**Computerized Shipley-2 
X  
 
 
Fagerstrom (FTND) 
 
X 
 
Brief Substance Craving Scale (BSCS) 
 
X 
 
PTSD Checklist for DSM5 (PCL5) 
 
X 
 
WHOQOL BREF 
 
X 
 
**Family Tree Questionnaire 
X  
  
 
**Trauma History Questionnaire (THQ) 
X  
 
 
Positive and Negative Affect Schedule (PANAS) 
 
X 
 
Toronto Alexithymia Scale (TAS-20) 
 
X 
 
**Relationship Scale Questionnaire (RSQ) 
X  
  
 
MPQ-NEM 
 
X 
 
WHO-DAS 
 
X 
 
**VAS-Pain 
X  
  
 
Attentional Network Test (ANT) 
 
X 
 
Hypothetical Purchase Task 
 
X  
 
Stop Signal Reaction Task 
 
X 
 
 
Screening 
Assessment 
visit 
MRI visit 
Visual Digit Span (backward recall) 
 
X 
 
5-Trial Adjusting Delay Discounting 
 
X 
 
Emotional Go/Nogo Task 
 
X 
 
SUPPS-P 
 
X 
 
Cue Interference Task-Attentional Bias Line Counting 
 
X 
 
Distress Tolerance Scale 
 
X 
 

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PROMIS-Depression Scale 4a 
 
X 
 
PROMIS-Anxiety Scale 4a 
 
X  
 
Buss Perry Aggression Questionnaire 
 
X 
 
Snaith-Hamilton Pleasure Scale 
 
X 
 
Metacognitions Questionnaire (MCQ-30) 
 
X 
 
MAIA 
 
X 
 
Pittsburgh Sleep Quality Index-Revised 
 
X 
 
Debriefing Questionnaire 
 
X 
 
Adverse Events 
 
X 
X 
MRI scan 
 
 
X  
Edinburg Handedness Questionnaire 
X 
 
 
^ Opioid Craving Scale 
X 
X 
X 
^ Opioid Intoxication Scale 
X 
X 
X 
24 Hour Survey 
 
 
X  
Resting State Questionnaire 
 
 
X  
 
Note:  Many of the assessments are available for download through the Millisecond Test Library  
(www.millisecond.com). Millisecond Software, LLC, is a provider of software for psychological 
testing.  All tests in the Millisecond Library are free with an Inquisit license or with the Inquisit 
Lab free trial. 
 
*  Denotes procedures that will be completed only for individuals who are eligible for screening 
for MRI portion of the study (Healthy Controls and individuals with OUD).   
 
** If time is available, this task will be completed at Screening Visit, otherwise, the task will be 
completed at the Phenotyping Assessment Visit.   
 
^ The Opioid Intoxication Scale will also be completed with individuals who test positive for 
opioid use during the mock scan and/or MRI visit(s). The Opioid Craving Scale will also be 
administered to individuals with OUD at each visit.   
 
7.2   Subject Recruitment and Consenting   
 
Subjects will be recruited from participants included in the CARI screening repository (VCU 
IRB# HM20000294, Keyser-Marcus (PI)) and from local advertising.  Individuals who have 
previously completed the CARI universal screening protocol (through HM20000294) and are 
determined to be eligible for an on-site screening visit, will be contacted to determine study 
interest.  Interested individuals will be scheduled for an on-site screening visit. 
 
Individuals who present for the screening visit will undergo the informed consent process.  The 
consent procedure fully apprises individuals of rights and responsibilities of study participants.  
Consent is conducted by study personnel in a private office. During the consenting process, 
potential participants will be given the opportunity to ask questions throughout and have all of 
their questions answered prior to making a decision regarding whether or not to participate.  All 
consent and study procedures and materials will be approved by the VCU IRB.  All subjects will 
provide informed written consent prior to any data collection. During the informed consent 
process it will be made clear to all subjects that this is not a treatment study.  A community 
resource brochure will be offered to all study participants, regardless of group assignment.  The 
resource brochure includes information on substance abuse treatment providers in the 
Richmond area.  

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7.3  Screening 
 
The screening assessment will take place during the same visit as the consent/enrollment into 
the study.  It is estimated to take between 60 and 90 minutes for subjects to complete screening 
procedures.   
 
Screening assessment used to determine study eligibility will include (may not in that 
particular order as in below):  
A Demographics Questionnaire will be used to assess standard sociodemographic 
information, including age, racial/ethnic background, sex, educational attainment, employment 
status, occupation, and marital status.  
 
Participant Locator Form The Participant Locator form collects information (e.g., name, 
address, telephone number, email) for the participant and phone numbers for up to three other 
people whom the participant states are familiar with his or her whereabouts and who might 
assist with contact efforts if study personnel are unable to reach the participant.  
 
The Mini International Neuropsychiatric Interview V 7.0.2 (MINI) (Sheehan et al, 1998) will 
be used to collect diagnostic information used to make eligibility determinations. DSM-5 
diagnoses (including Cocaine Use Disorder and Opioid Use Disorder) will be ascertained for all 
subjects. Interviews will be conducted by experienced research personnel who have 
successfully completed standardized training in the administration and scoring of the MINI.  
 
Columbia Suicide Severity Rating Scale (C-SSRS).  (Posner et al., 2009) is an interview 
measure used to assess suicidal ideation and behavior. The Baseline version is used during 
screening and collects information related to lifetime suicidal ideation and behavior. The Since 
Last Visit version assesses suicidal ideation and behavior in the time since the last patient visit, 
and will be used at the subsequent study visit. 
 
The CARI Medical Survey will be used to collect information regarding medical history on all 
potential subjects, and the Concomitant Medications form will be used to collect information 
regarding current over-the-counter and prescription medications used by potential participants. 
Vital signs to be assessed include oral temperature, sitting blood pressure, pulse, respiratory 
rate, and weight. Urine specimens will be collected for pregnancy testing (females only), as well 
as urine drug screen for cocaine (benzoylecgonine), opiates and opioids, benzodiazepines, 
amphetamine, methamphetamine, and THC.  Breath alcohol and carbon monoxide (for recent 
tobacco use) levels will also be obtained. 
 
Upon completion of the screening assessments listed above, individuals who screen as 
ineligible will be compensated for their time and effort and informed that they are ineligible to 
participate in the study.  Individuals who are deemed eligible for the study will go on to complete 
a portion of the Platform Battery (listed below) assessments during this visit, if time permits.  If 
the participant has to leave prior to completing these assessments, they will be completed at the 
Phenotyping Assessment Visit.   
 
 
 
MRI Eligibility Screening  

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Individuals in the Healthy Control and Opioid Use Disorder groups will also be eligible to 
screen for the MRI portion of the study.  The MRI screening consists of the following: 
 
Medical and Laboratory Evaluation, which will include a physical examination (including 
neurological exam and medical history), MRI safety screening, and a blood draw for complete 
blood count (CBC).  
 
Mock MRI scanning session: Healthy control and OUD subjects who are deemed eligible for 
MRI scanning, based on results of the physical exam and MRI screening checklist, will also 
complete a mock MRI scanning session. During the mock session, participants are allowed to 
practice tasks in a MRI Simulation Device (mock MRI machine). During the computer 
demonstration prior to the simulator sessions, subjects are allowed up to 10 min of practice 
(with interaction permitted with the research assistant), until it is clear that the procedures are 
understood and that the majority of the practice responses are correct. During simulator 
sessions, tasks are projected by an LCD projector on a screen that the subject views using 
mirror-prism glasses. The subject listens to a recording of MRI sounds during the simulator 
sessions.  Participants will also complete the Edinburgh Handedness inventory in order to 
determine their dominant hand across a number of tasks.  Self report of recent drug use will 
also be collected.  Participants will also complete the 24-hour Survey at both the mock MRI 
scan visit and the MRI scan visit, in order to document consumption of caffeinated beverages, 
alcohol and tobacco use in the past 24 hours.  The Opioid Intoxication Scale will also be 
completed with individuals who test positive for opioid use during the mock scan and/or MRI 
visit(s). The Opioid Craving Scale will also be administered to individuals with OUD at each visit.  
Finally, the Resting State Questionnaire will be administered following the MRI scan.   
 
 
Upon completion of the screening visit, CARI research staff will inform participants of their 
eligibility to complete the study. Eligible participants are then scheduled to return to the clinic to 
complete the study assessment visit. Individuals who are not eligible will be notified of their 
ineligibility, compensated $30 (non MRI candidates) or up to $70 ($70 for MRI candidates who 
complete the mock scanning session, or $50 for MRI candidates who do not complete the MRI 
scanning session), and thanked for their time.  
 
Note:  Individuals who have already completed the Phenotyping portion of the protocol, and 
have been recontacted and reconsented to participate in the MRI portion of the study will 
complete a MRI screening visit, which will consist of the same MRI screening procedures listed 
above.  
 
7.4  Phenotyping Assessment Visit 
 
As described above, the Assessment Visit will consist of the the remaining measures included in 
the Platform Instrument Battery, and all of the measures included in the Phenotyping Battery.  It 
is estimated to take approximately 3.5 - 4 hours to complete both (with scheduled rest breaks 
included).  Upon arrival to the clinic, participants will first complete biological measures, which 
includes vital signs (oral temperature, sitting blood pressure, pulse, respiratory rate, and 
weight), urine and breath samples.  Urine specimens will be collected for pregnancy testing 
(females only), and urine drug screen for cocaine (benzoylecgonine), opiates and opioids, 
benzodiazepines, amphetamine, methamphetamine, and THC.  Breath alcohol and carbon 
monoxide (for recent tobacco use) levels will also be obtained.   
 

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7.4.1 Assessment Measures  
 
Platform Instrument Measures.  Platform instruments will not be administered in the fixed 
sequence as in below. Efforts will be made to administer as many of the Platform Instruments 
marked with an asterisk (*) at the time of the Screening Visit (as time permits). Otherwise, they 
will be administered during the Phenotyping Visit.   
 
* Computerized Shipley-2. Brief, but robust measure of cognitive functioning and impairment 
that assesses both crystallized and fluid cognitive ability (Shipley, Gruber, Martin, and Klein, 
2009). Estimated time to complete 20 minutes. The Shipley-2 has been shown to be 
psychometrically sound, with moderate to high test-retest reliability correlations (.74 to .94) 
across a 1-2 week delay, and good internal consistency, discriminative validity, and strong 
concurrent validity with WAIS-III, PIQ, and VIQ ( with correlations ranging from .62- .87).   
 
* Adult Self-Report Symptom (ASRA) Checklist (ADHD). A brief self-administered inventory 
consisting of 18 questions which aids in assessing symptoms of ADHD/ADD. Estimated time to 
complete is 1-5 minutes. It has demonstrated high rates of internal consistency for both self-
report and rater-administered versions (Cronbach’s alpha 0.88, 0.89, respectively) and high 
concurrent validity with the rater administered ADHD RS (Adler, Spencer, et al, 2006) 
 
* Recent Life Events Questionnaire (Adults). (Brugha, Bebington, et al, 1985), Is a 21-item self-
administered scale used to assess recent (past 12 months) life events, as well as their current 
impact on the respondent. 
 
* Family Tree Questionnaire (FTQ) for Substance Use. A self-report family history measure that 
assists in identifying of first- and second-degree relatives with alcohol and other substance use-
related problems (Mann, Sobell, Sobell, & Sobell, 1985).  Reliability studies have demonstrated 
good test-retest reliability, and validity studies have shown criterion and concurrent validity of 
the instrument. 
 
* Trauma History Questionnaire (THQ).  A 24-item self report measure of physical and sexual 
abuse (ever in lifetime), which includes items related to crime-related events and general 
disaster/trauma.  Respondents are asked to provide the frequency of the event and their age at 
the time of the event. The THQ has been found to be psychometrically sound with regard to 
both reliability and validity (Hooper, Stockton, Krupnick, & Green, 2011) 
 
* Relationship Scale Questionnaire (RSQ)  A 30-item self-report questionnaire that assesses 
attachment style. Subjects rate on a 5 point scale, the extent to which each statement describes 
them in close relationships from “Not at all like me” to “Very much like me”. (Griffin and 
Bartholomew, 1994).  Previous research has suggested that the RSQ demonstrates good test-
retest reliability and internal consistency (Guédeney,  Fermanian, & Bifulco 2010).  
 
* Visual Analog Scale for Pain (VAS-pain). 100mm visual analog scale used to obtain patient 
rating for current magnitude of pain experienced, with endpoints defining extreme limits such as 
‘no pain at all’ and ‘pain as bad as it could be’ (Wewers & Lowe, 1990) 
 
Timeline Follow Back for Drug, Alcohol, Tobacco use  (Sobell and Sobell, 1996).  Structured 
interview that queries quantity of daily drug,alcohol and tobacco use over a specified time 
period. Using a calendar, respondents provide retrospective estimates of their tobacco, alcohol 

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and/or drug use.  This method has demonstrated solid psychometric properties across a variety 
of populations (Robinson, Sobell, Sobell, & Leo, 2014). 
 
Fagerström Test for Nicotine Dependence (FTND) (Heatherton et al, 1991; available in the 
Millisecond Test Library). A widely used 6-item self-report questionnaire designed to measure 
nicotine dependence, The items are summed to yield a total score of 0-10, with higher scores 
indicating greater nicotine dependence.   
 
Brief Substance Craving Scale (BSCS; available in the Millisecond Test Library). The BSCS is a 
16 item, self-report instrument assesses craving intensity and frequency of craving for cocaine 
and other substances of abuse over a 24-hour period.  Items are rated on a five-point Likert-
type scale (Somoza, Dyrenforth, Goldsmith, Mezinskis, & Cohen, 1995).  
 
PTSD Checklist for DSM5. (PCL5; available in the Millisecond Test Library) A 20-item 
questionnaire based on DSM5 criteria for PTSD,with each item being assigned a severity score 
of 0-4, yielding a total symptom severity score ranging from  0-80  The PCL5 has been shown to 
exhibit strong internal consistency (α = .94), and test-retest reliability (r = .82), as well as  
convergent and discriminant validity (Blevins, Weathers, Davis, Witte, & Domino, 2015).  
WHO QOL Bref. (available in the Millisecond Test Library). A 26-item questionnaire assessing 
quality of life in 4 domains: physical, psychological, social and environmental (WHOQOL Group, 
1998). Reliability and validity data indicate that the WHOQOL-BREF has good to excellent 
internal consistency, item–total correlations, and discriminant validity and construct validity 
(Skevington, Lotfy, & O’Connell, 2004)  
Positive and Negative Affect Schedule (PANAS-20; available in the Millisecond Test Library). A 
20-item measure assessing positive and negative affect, on a scale from 1 to 5 (Watson et 
al.1988). Reliability and validity reported by Watson (1988) was moderately good, with the 
Cronbach alpha coefficient ranging from 0.84 to 0.90, and test-retest correlations ranging from 
0.39-0.71 over a 8-week time period. 
 
Toronto Alexithymia Scale (TAS-20; available in the Millisecond Test Library). A 20-item self-
report questionnaire to assess emotional awareness. The measure is divided into three 
subscales: Difficulty Describing Feelings, Difficulty Identifying Feelings, and Externally-Oriented 
Thinking.  Items are rated on a 5 point Likert-type scale, from 1 (strongly disagree) to 5 (strongly 
agree).  The TAS-20 demonstrates good internal consistency (Cronbach’s alpha = .81) and test-
retest reliability (.77, p<.01), as well as adequate levels of convergent and concurrent validity 
(Bagby, Parker & Taylor, 1994). 
 
Multidimensional Personality Questionnaire- Negative Emotional Temperament (MPQ-NEM). 
(Tellegen,1995). A 40-item scale on the MPQ that assesses individual trait differences in 
affective reactivity: primary scales of Stress Reaction, Alienation, and Aggression. High scores 
on the MPQ NEM factor indicate greater anxiety, anger, and related negative emotions and 
behavior. The MPQ has strong psychometric properties and good behavioral genetic data from 
twin studies (McGue, Bacon, & Lykken, 1993). 
 
WHO Disability Assessment Schedule (WHO-DAS; available in the Millisecond Test Library).  A 
12 item generic assessment for health and disability linked to ICF (International Classification of 
Functioning, Disability and Health).  A Normative data for the 12 item version of the WHODAS 

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2.0. found that scores of  10–48 accurately identify individuals with a clinically significant 
disability (Andrews, Kemp, Sunderland, VonKorf, & Ustun, 2009).  
 
Levenson Self-Report Psychopathy Scale (LSRP; available in the Millisecond Test Library). A 
26 item self-report scale, in which respondents rate each item on a scale from 1 (strongly 
disagree) to 4 (strongly agree.  Items included in the scale reflect both primary psychopathy 
(callous, manipulative, and selfish use of others) and secondary psychopathy (impulsivity and 
poor behavioral controls;  Levenson et al, 1995). 
Phenotyping Assessment Battery (PhAB)  Measures. 
 
Measures will be administered in non-fixed order. After NIDA Phenotyping Battery Measures 
administration subjects will complete Debriefing/Satisfaction survey. After Interim Data Analysis 
(see Section 8.4) the order of measures administration can be changed and the order may 
become fixed. 
 
   
 
Attentional Network Test (ANT; available in the Millisecond Test Library):  Cue-target test using 
reaction time to measure Alerting, Orienting, Executive Control. Our focus is on Executive 
Control. Single testing session, 1 block test 9 min, connects with neuronal networks. (Fan, 
McCandliss, Sommer, Raz & Posner, 2002). 
  
Stop Signal Reaction Task  ((SST) available in the Millisecond Test Library)  A measure of 
response inhibition in which subjects perform a “go task” in response to a stimulus, and 
occasionally the go stimulus is followed by a “stop signal”, which requires subjects to withhold 
the go response (Verbruggen et al, 2008). . 
 
Hypothetical Purchase Task.  A time- and cost-efficient simulation procedure to assess 
reinforcement efficacy in humans. Respondents answer questionnaires asking how much of a 
particular substance (e.g., bags of heroin) they would purchase across a range of prices within a 
fixed period of time. (Jacobs & Bickel, 1993). 
 
Visual Digit Span (backward recall; available in the Millisecond Test Library):  Brief 
(approximately 5 minutes) commonly used test of working memory, in which subjects are tasked 
to recall (in reverse order) a sequence of numerical digits presented to them via computer.  
Increasingly longer sequences are added in each subsequent trial. (Wechsler, 1997). 
 
5-Trial Adjusting Delay Discounting task  (available in the Millisecond Test Library; Koffarnus & 
Bickel, 2014). A brief task designed to obtain a subject’s discount rate in less than one minute.  
Based on the premise that individuals tend to value rewards less as the amount of time 
increases until those rewards would be received. 
 
Emotional Go/Nogo Task (Tottenham, Hare  & Casey, 2011; will be available in the Millisecond 
Test Library).  Task designed to assess cognitive control in the context of emotional information 
as a measure of emotion regulation.  Mix of behavioral inhibition with embedded probe of 
attentional capture by emotional/social cues.   
 
SUPPS-P (available in the Millisecond Test Library).  A 20-item version of the original UPPS-P 
questionnaire, used to assess self-reported personality traits associated with impulsive behavior 
across five dimensions: urgency,  premeditation, perseverance, sensation seeking, and positive 
urgency (Whiteside & Lynam, 2001) 
 

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Cue Interference Task- Attentional Bias Line Counting Task  (will be made available in the 
Millisecond Test Library).  A modified version of a previously developed attentional bias task 
(Passamonti, Luijten, Ziauddeen, et al, 2017), which measures the degree by which people are 
distracted by drug cues, will be used in the present study. 
 
Distress Tolerance Scale (DTS) (available in the Millisecond Test Library). A 15-item self report 
measure of emotional distress tolerance.  Items are loaded across 4 factors:  tolerance, 
absorption, appraisal, regulation (Simons & Gaher, 2005) 
 
PROMIS- Depression scale.  A brief (4-item) self-report measure which assesses four domains 
of depression: negative mood, views of self, social cognition, and decreased positive affect and 
engagement.  With regard to psychometric characteristics, Choi and colleagues (2010), found 
that the short form scores were highly correlated with the longer PROMIS measures.  
 
PROMIS- Anxiety.  A brief (4-item) self-report measure which assesses anxiety symptoms (e.g., 
hyperarousal), experienced in the past 7 days..  Subjects rate the frequency of experiencing 
each symptom, on a 5-point Likert-type scale, from 1 (never) to 5 (always).    
 
Buss Perry Aggression Questionnaire- 29 item self measure of aggression.  Participants rank 
statements along a 7-point Likert-type scale, ranging from 1 (extremely uncharacteristic of me) 
to 7 (extremely characteristic of me).  The measure includes four subscales: physical 
aggression, verbal aggression, anger, and hostility (Buss & Perry, 1992).  
 
Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al, 1995).  Available in the Millisecond Test 
Library.  A 14-item scale which measures anhedonia.  Previous research has found the SHAPS 
has adequate construct validity and test-retest reliability (ICC=0.70) as well as high internal 
consistency (Cronbach’s alpha of 0.94) among both clinical and nonclinical populations 
(Franken et al, 2007).  
 
Metacognitions Questionnaire-30 (MCQ-30; available in the Millisecond Test Library). A brief 
(approximately 5 minutes) self-report measure of metacognitive beliefs associated with the five-
factor metacognitive model of psychological disorders, including: cognitive confidence, positive 
beliefs about worry, cognitive self-consciousness, negative beliefs about uncontrollability of 
thoughts and danger, and beliefs about the need to control thoughts.  The MCQ-30 has 
demonstrated good internal consistency, convergent validity, and test-retest reliability (Wells 
and Cartwright-Hatton 2004). 
 
Multidimensional Assessment of of Interoceptive Awareness (MAIA; available in the Millisecond 
Test Library).  A 32-item self-report measure that assesses awareness of body sensations, 
including the emotional/physiological state, physical discomfort and pain.  Items are rated on a 6 
point Likert-type scale, ranging from 0 (never) to 5 (always) (Mehling, Price et al. 2012). 
 
Pittsburgh Sleep Quality Index-Revised ((PSQI) available in the Millisecond Test Library) A brief 
questionnaire assessing sleep habits, including disruptions in sleep and influence of sleep on 
daily functioning during the past week. (Buysse et al.,1989). 
Concomitant Medication(s) 
All concomitant medications taken during the trial must be recorded with indication, daily dose, 
and start and stop dates of administration. Medications taken within 28 days before the start of 
the trial will be documented as a prior medication. Medications taken after the start of the trial 
will be documented as concomitant medications.  

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7.5   MRI Scan Visit 
 
Upon arrival to the clinic, participants will first complete biological measures, which includes vital 
signs (oral temperature, sitting blood pressure, pulse, respiratory rate, and weight), urine and 
breath samples.  Immediately prior to MRI scanning, urine from each participant is screened for 
amphetamine, barbiturates, benzodiazepines, cocaine, methamphetamine, MDMA (ecstasy), 
opioids (methadone, buprenorphine, morphine, codeine, heroin, hydrocodone, hydromorphone, 
levorphanol, oxycodone, and oxymorphone), phencyclidine, propoxyphene, tricyclic 
antidepressants, and THC.  Breath alcohol and carbon monoxide (for recent tobacco use) levels 
will also be obtained.  Self report of recent drug use will also be collected.  Participants will also 
complete the 24-hour Survey at both the mock MRI scan visit and the MRI scan visit, in order to 
document consumption of caffeinated beverages, alcohol and tobacco use in the past 
24 hours.  The appropriate Drug Intoxication Scale(s) (cocaine/opioid/marijuana) will also be 
completed with individuals who test positive for opioids, cocaine, and/or marijuana during the 
mock scan and/or MRI visit(s). The Opioid Craving Scale will also be administered to individuals 
with OUD at each visit.  Finally, the Resting State Questionnaire will be administered following 
the MRI scan.  
 
As an additional measure of phenotyping related to the neurobiology of drug addiction, a subset 
of participants (OUD primary (n=50), and HC (n=50)), will undergo an MRI scan consisting of a 
resting state fMRI and structural scans. Brain connectivity measures will be determined 
using functional and effective connectivity analyses. 
 
The scan session will last approximately 80 minutes from the time of successful position 
of while the participant’s head is in the scanner bore, including time for individual scan setups. 
The session consists of each of the following scans:  1) Localizer, 2) resting-state fMRI scan, 
during which the participant is asked simply to look at a crosshair, 3) T2 FLAIR scan for 
incidental pathology, 4) Structural T1-weighted MP-RAGE scan for calculation of brain 
volumes and co-localization of brain signal across different participants, 5) Drug-word Stroop 
task (see description below), 6) Two runs of the XY-GoNoGo task (see description below), 7) 
PRESS Spectroscopy sequence to assess concentrations of glutamate, choline, creatine, N-
acetyleaspartate and other metabolites in the anterior cingulate cortex , 8) and Mega-PRESS 
spectroscopy sequence to assess concentrations of GABA in the anterior cingulate cortex.  MR 
spectroscopy will be performed on the ACC region and will use Point-Resolved Spectroscopic 
Sequence (PRESS).  The MRS scan is approximately 4.5 mins.  MRS analysis for PRESS 
spectra will be performed by using the Java-based Magnetic Resonance User Interface 
(jMRUI).  Specialized MRS of GABA and other metabolites will be performed using a Mescher-
Garwood PRESS (MEGA-PRESS) sequence.  The total time for this sequence is approximately 
9 mins.  MEGA-PRESS data will be analyzed with the MATLAB-based tool Gannet.  In MR 
spectroscopy, the subject will experience nothing different compared to other MRI scans in 
the study.   Prior to each fMRI run, two EPI images with the same echo time and spacing as the 
main run are acquired with opposite phase-encode directions (less than 60 s duration). From 
this scan pair, susceptibility-induced off-resonance field correction is estimated using the 
method implemented in FSL "topup" software. In addition, peripheral pulse rate (using MRI 
compatible pulse oximeter) and respiratory rate (using standard MRI respiratory chest belt) will 
be recorded during the fMRI scans for removing artifactual physiological signals 
using the “retroicor” software. 
 

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XY Go-NoGo task  This task probes brain responsiveness to sporadic requirements to inhibit 
prepotent motor behavior.  The subject must periodically interrupt a general stream of cue-
elicited motor responses that are elicited once per second. The subject sees a sequence of 
either the letter X or the letter Y presented in the middle of the screen once per second (i.e. 1 s 
trial; stimulus duration = 400 to 600 ms).  The remaining time of each one-second trial is 
composed of blank screen).  The subject is instructed to respond to each letter if it is different 
than (i.e. alternates with) the previous letter.  Periodically, the subject will see a second X or a 
second Y presented in a row, and must withhold his or her response.  The scan task will be 
performed in two fMRI runs (5 minutes each).  During task performance, an indicator LED light 
flashes in the scanner control room with each button press, thereby alerting the research staff of 
subject engagement in the task in real-time. 
 
 Drug Word Stroop Task  Participants see opioid words (OWs) and neutral words (NWs) within 
four alternated 30-s OW blocks and NW blocks. Each presented word is randomly printed in 
blue, green, or red. The participant is instructed to ignore the meaning of the word and to press 
a button to denote the word color. For each participant, the mean reaction times (RTs) during 
the OW blocks and during the NW blocks are computed. The effect of opioid cues on the 
reaction time (ΔRT) are measured by the mean RT during all the correct-response trials in the 
OW blocks minus the mean RT during all the correct-response trials in the NW blocks, i.e., ΔRT 
= RT (OW) minus RT (NW). ΔRT is treated as the behavioral measure of attentional bias. 
 
 
 
 
 
 
 
7.6  Participant Reimbursement 
All participants will receive $40 for completing the screening visit and $75 for completing the 
assessment visit, for a total of up to $115 for completing the assessment battery portion of the 
study.   
 
Additionally, individuals who are eligible to screen for the MRI portion of the study (Healthy 
Controls and individuals with OUD) will receive up to an additional $75 for screening ($25 for the 
additional screening measures-  the physical exam and blood draw,  and $50 for the mock MRI),  
and $100 for the MRI (for up to $290 for completing both the assessment battery portion and 
MRI portion of the study).  Payment will be in the form of cash. Participants who are returning 
only to complete the MRI screening/scanning portion of the study will receive up to $75 for the 
MRI screening ($25 for physical exam and blood draw, and $50 for mock MRI), and $100 for the 
scan visit.   
 
The pro-rated compensation schedule for individuals who do not complete a given study visit is 
as follows:   
Participants will receive $10 per hour for a study visit (with the maximum available $40 for 
individuals in marijuana and cocaine groups and up to $115 for individuals in the healthy control 
and opioid use disorder groups for screening, maximum of $75 for assessment visit (regardless 
of group status), and a maximum of $100 for the MRI visit) if they do not complete a given study 
visit. 
All participant payment will be in the form of cash.   
 
Resting 
T2 
0
3 min
18
23
30
37
44
50
57
69 min
Struct 
PRESS 
Stroop 
XYGNG
L 
XYGNG 
mPRESS 
DTI 

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8.  DATA MANAGEMENT PROCEDURES 
 
8.1 Data Collection 
  
Individual subject data will be obtained via structured interview evaluations, self-report 
measures, and computerized behavioral tasks. This information will be collected at specified 
time points during the study.  The biological specimens obtained from all subjects will include 
urine, and breath samples for alcohol detection.  All materials will be obtained for the specific 
purposes of this research.  Trained research personnel will collect study data according to 
written protocol.  
 
8.2.  Data Entry and Validation 
 
In an effort to enhance efficiency and accuracy of the data, hard copy self-report measures will 
be converted into electronic data capture forms (using REDcap electronic data capture system) 
for direct computer-based entry by study participants.   Remaining self-report and interview data 
will be entered by research assistants into an existing, secure database (i.e. REDcap).  Data 
integrity will be maintained by restricting allowable input values on a standardized entry forms.  
Double entry of a random subset of 10% of the observations will be used to identify problematic 
data entry issues.    
 
8.3.  Interim Analysis & Full Data Analysis 
The primary data analyses will focus on final modifications to the PhAB and Platform 
battery. Data will be evaluated over all enrolled subjects. Number and percentage of 
dropouts, non- completers of the PhAB Battery and Platform Instrument measures will be 
assessed. Time to complete the assessment batteries will also be recorded for each task 
and each participant. Findings with regard to average time to complete each measure, 
redundancy between assessments, and sensitivity and specificity of measures will guide 
decisions on the refinement of the battery and the selection of instruments to be included in 
the final version of both the Platform instrument and PhAB assessment batteries. Additional 
analyses will focus on examining relationships between task performance, assessment 
response patterns, and SUD diagnoses, and how these relationships vary according to 
various other psychosocial influences (e.g., trauma, gender, depression, etc). 
 
Effective connectivity analyses of resting state scans will be performed using dynamic 
causal modeling (DCM) in SPM. Effective brain connectivity will be compared between 
OUD, other relevant populations in the study and control participants and the relationship 
between effective brain connectivity and behavioral assessments from the PhAB will be 
assessed. Default mode and executive control networks will be the primary networks 
studied in this analysis. In addition, a effective connectivity brain analysis will be 
conducted in order to test the group difference in a large extent covering the whole brain. 
A preliminary functional connectivity analysis will be conducted in a large brain network to 
detect the brain regions showing largest group difference in functional connectivity. Nodes 
showing largest group difference in functional connectivity will be selected as DCM nodes 
for the large extent effective brain connectivity analysis.   
 
 

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9.  SAFETY MONITORING AND REPORTING 
 
The study PI is ultimately responsible for safety monitoring and adherence to the protocol, and 
will review all safety monitoring and study performance data and address any problems noted.  
 
 
 
9.1 Subject protection 
 
Subjects might experience psychological distress due to assessment procedures.  It is not 
anticipated that serious psychiatric problems (including suicidality) will develop 
while participating in the study. If such an event occurs (whether or not it 
is thought to be study-related), the study team is experienced in handling these events and will 
follow clinic guidelines and immediately contact the appropriate study doctor and/or PI for 
evaluation.  The participant will be referred for appropriate medical or psychiatric care as 
needed.  It is more likely that during the clinic visits, participants may 
experience some degree of emotional discomfort or fatigue due to the screening and/or 
assessment procedures. However, the use of these procedures has not been shown to be 
harmful to psychiatric/substance abusing patients. In an effort to minimize the risk of distress 
and/or fatigue experienced by participants, breaks will be given at regular intervals and as 
needed, and participants will be informed that they have the right to refuse to answer questions 
that make them uncomfortable. Additionally, research personnel are trained to assess for level 
of distress and will be attentive to the participant’s needs.  
 
Confidentiality of patient records is maintained by assigning subject ID numbers and 
using these rather than subject names on all study records. Research data are kept in a 
locked filing cabinet; signed consent forms and subject ID keys are kept in a separate 
location in a locked cabinet.   
 
 
9.2 Adverse event monitoring and reporting 
 
An adverse event (AE) is defined as any untoward medical occurrence in a participant 
that may or may not have a causal relationship with study participation. Any mention of an 
untoward event will trigger an entry onto the AE log. All adverse events (AEs) occurring during 
the course of the study will be collected, documented, and reported to the PI. The occurrence of 
AEs will be assessed at baseline.  Due to the nature of the current study, it is anticipated that a 
low number of study-related adverse events will occur. However, potential adverse events may 
include: psychological distress due to assessment procedures. Relapse to substances requiring 
hospitalization, drug overdose, and suicidality may also occur.  A summary of AEs will be 
provided to the VCU IRB at the time of protocol continuing review, and will also be provided to 
NIDA Program Officer (Dr. Aidan Hampson) and Science Officer (Dr. Tanya Ramey).   
 
9.3 Serious adverse event monitoring and reporting 
 
A serious adverse event (SAE) is defined as any event that is fatal or life threatening, that 
is permanently disabling, requires or extends hospitalization of the subject, is a congenital 
anomaly, or requires intervention to prevent any of the above. This could include 
hospitalizations related to drug overdose or suicidality.  
 

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AE’s deemed to be serious (SAEs), as defined by the FDA, will be systematically evaluated at 
each clinic visit. Study-related SAEs, will be reported to the VCU IRB, and the NIDA Program 
Officer within 24-48 hours. A full written report to all institutions will follow as soon as possible 
but in no more than three days.  The written report will be in the format required by the local IRB 
and will contain information regarding the date of the SAE, description of the SAE, severity 
rating (Grade 1 to 4), assessment of cause, whether the SAE indicates an increased risk for 
current or future subjects, and whether changes to the informed consent form will be necessary.   
 
 
9.4 Criteria for Participant Discontinuation from the Study 
 
The reasons for discontinuation from the study may include: inability to comply with study 
procedures, change in study eligibility, or exhibiting potential harm to self or others.  Participants 
must continue to meet inclusion criteria in order to remain in the protocol. If suicidal ideation is 
identified in any subjects while actively enrolled in the study, the subject will be withdrawn from 
the study. The study physician will be contacted immediately and meet with the subject. If the 
participant expresses having a plan, the subject will not be left alone until a study physician has 
met with him/her. A trained study staff will remain with the subject until a study physician meets 
with him/her or until the subject has been seen by a study psychiatrist for an emergency 
psychiatric consultation. A physician will be available at all times to assess the situation. If the 
study physician determines that the subject’s suicidal risks are high, he/she will develop a plan 
for safety will the subject, including but not limited to: transferring the patient to the psychiatric 
unit of the VCU medical center.  
 
In the event that a patient either withdraws from the study or the investigator decides to 
discontinue a patient due to SAE, the patient will have appropriate follow-up monitoring. 
Monitoring will continue until the problem requiring hospitalization has resolved or stabilized with 
no further change expected, is clearly unrelated to study, or results in death.  
 
10.  Institutional Review Board (IRB)/Independent Ethics Committee(IEC) 
 
It is the responsibility of the investigator to have IRB approval of the study protocol, protocol 
amendments, informed consent forms, and other relevant documents, eg, advertisements, if 
applicable, from the IRB/IEC.  All correspondence with the IRB/IEC should be retained in the 
Investigator File.  Copies of IRB/IEC approvals should be forwarded to NIDA Science Officer (Dr 
Tanya Ramey). 
 
 
 
 
 
 
 
 
 
 
 
 

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