Clinical trial NCT03226223
Conditions: Substance Use Disorders Methamphetamine Abuse
Sponsor: New York State Psychiatric Institute
Start date: 2016-09-15; Completion date: 2020-07-30
Enrollment: 18 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This investigation will be the first study assessing genetic modulation of naltrexone's NTX effects upon the abuse liability of a stimulant drug (methamphetamine). The study team will assess the ability of oral NTX to block the reinforcing and positive subjective effects of intranasal (IN) methamphetamine (30mg/70kg). This investigation could identify an important Gene x Pharmacological interaction, contributing to the personalization of stimulant abuse pharmacotherapy.

Detailed description:
A recent meta-analysis concluded that the OPRM1 A118G SNP (rs1799971) significantly moderates the treatment efficacy of Naltrexone (NTX) in treating alcohol abuse, increasing the treatment efficacy by over 2-fold among G-allele carriers (AG/GG). The proposed application would be the first to investigate the moderating effect of this genotype in the efficacy of NTX to treat stimulant abuse. More specifically, the study team proposes to investigate the interaction between NTX and intranasal (IN) methamphetamine (30mg/70kg). Participants who meet DSM criteria for mild-to-severe stimulant use disorder (N=up to 70) will complete 4 testing sessions where drug effects are tested following pretreatment with NTX (0, 50 mg). Naltrexone pretreatment effects upon the abuse liability of IN methamphetamine will be assessed using self-report measurements of positive subjective effects and drug self-administration. Medication effects on these validated predictors of abuse potential will be compared between A118G A allele homozygotes (AA) and G-allele carriers (AG/GG; an anticipated 25% of the total sample), in order to assess genetic moderation of treatment outcome.

Arms: arm 1: This aim assess the effects of pretreatment with 0 mg of naltrexone on laboratory measures of the abuse potential of methamphetamine (30mg/70 kg). arm 2: This aim assess the effects of pretreatment with 50 mg of naltrexone on laboratory measures of the abuse potential of methamphetamine (30mg/70 kg).
Interventions: intervention 1: Intranasal Methamphetamine
Intervention descriptions: intervention 1: Intranasal Methamphetamine HCL administered at a dose of 30mg per 70 kg of the participants' body weight)

Protocol documents:
Prot_SAP_000.pdf: 
Signed copy on file at IRB 
 
             v. 4/19/13 
                                          NEW YORK STATE PSYCHIATRIC INSTITUTE         
INSTITUTIONAL REVIEW BOARD 
MEMORANDUM 
 
 
 
 
 
 
 
 
 
January 10, 2017 
TO: 
 
Dr.  Jermaine Jones 
FROM: 
Dr. Edward Nunes, Co-Chair 
 
 
Dr. Laurence Greenhill, Co-Chair 
 
SUBJECT: 
APPROVAL NOTICE 
 
Your protocol # 7347 entitled USING PHARMACOGENETICS TO BETTER EVALUATE NALTREXONE 
FOR TREATING STIMULANT ABUSE (version date 01-10-17) and consent forms have been 
approved by the New York State Psychiatric Institute - Columbia University Department of 
Psychiatry Institutional Review Board from January 10, 2017 to November 6, 2017.  (Reviewed 
by the Full Board on 11-07-16.) 
 
Consent requirements: 
      
      Not applicable: 
           
     √ 45CFR46.116(d) waiver or alteration of consent (phone screen only) 
 
     √ Signature by the person(s) obtaining consent is required to document the consent process.                
 
      Documentation of an independent assessment of the participant’s capacity to consent is also 
required. 
          
    Approved for recruitment of subjects who lack capacity to consent:  √ No      Yes           
 
 
    Field Monitoring Requirements: √ Routine      Special:                                    
 
√   Only copies of consent documents that are currently approved and stamped by the IRB 
may be used to obtain consent for participation in this study. 
√  A progress report and application for continuing review is required 2 months prior to the  
expiration date of IRB approval. 
√  Changes to this research may be not be initiated without the review and approval of the  
IRB except when necessary to eliminate immediate hazards to participants.  
√  All serious and/or unanticipated problems involving risks to subjects or others must be 
reported immediately to the IRB.  Please refer to the PI-IRB website at http://irb.nyspi.org 
for Adverse Event Reporting Procedures and additional reporting requirements.  
 
 
CC:  RFMH Business Office (R21 DA040225-01A1)  
 
 
ENC:  CFs (2), Advertisements, HIPAA forms (2) 
 
 
 
EN/LG/Scr 


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Protocol Title:
Using Pharmacogenetics to Better Evaluate 
Naltrexone for Treating Stimulant Abuse
Protocol Number:
7347
First Approval:
01/10/2017
Expiration Date:
11/06/2017
Version Date:
01/10/2017
Clinic:
Opioid Research Laboratory
Contact Principal Investigator:
Jermaine Jones, PHD
Email: jonesje@pi.cpmc.columbia.edu
Telephone: 646 774-6113
Co-Investigator(s):
Sandra Comer, PHD
Verena Metz, PHD
Research Chief:
Frances Levin, MD
Cover Sheet
Choose from the following that is applicable to your study
I am submitting a new protocol
Division & Personnel
Division
What Division/Department does the PI belong to?
Psychiatry
Within the division/department, what Center or group are you affiliated with, if any? 
Substance Abuse
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
N/A


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Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
   Psychiatric Assessment
   Collection of Biological Specimens
   Studies of DNA 
   Administration of Substance of Abuse
   Use of Investigational Drug or Device
Population
Indicate which of the following populations will be included in this research
   Medically and Psychiatrically Healthy Subjects
   Adults
   Substance Users
Research Support/Funding
Will an existing internal account be used to support the project?
No
Is the project externally funded or is external funding planned?
Yes
Select the number of external sources of funding that will be applicable to this study
Funding Source #1
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract application is a pending review or a funding decision
Source of Funding
Federal
Institute/Agency
NIDA
Grant Name
Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse
Grant Number
R21 DA040225-01A1
Select one of the following
Single Site
Business Office


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RFMH
Does the grant/contract involve a subcontract? 
No
Study Location
Indicate if the research is/will be conducted at any of the following
   NYSPI
This protocol describes research conducted by the PI at other facilities/locations
No
Lay Summary of Proposed Research 
Lay Summary of Proposed Research
Several preclinical and clinical studies have provided data suggesting that naltrexone (NTX) may have 
potential to block the abuse potential of stimulant drugs like amphetamines and cocaine. However, there are 
conflicting findings from the several studies investigating this question.  Studies have shown that  a 
variation in the mu opioid receptor gene (A118G) significantly affects the ability of NTX to block the 
effects of alcohol. The goal of this study is to investigate if this genotype may also affect the interaction 
between NTX and psychostimulant drugs. We propose to investigate the interaction between NTX and 
intranasal (IN) methamphetamine (30mg/70kg). White participants who meet DSM 5 criteria for mild-to-
severe stimulant use disorder and have a history of intravenous, intranasal or smoked use of 
amphetamine drugs, will complete testing sessions where drug effects are examined following 
administration of NTX (0, 50 mg). The effects of NTX on the the abuse potential of IN methamphetamine 
will be assessed using self-report measurements of positive drug effects and drug self-administration. NTX's 
effects will then be compared between A118G A allele (AA) and G-allele (AG/GG) groups, in order to 
assess genetic influence. Participants will submit blood samples for genetic analysis upon screening. DNA 
samples will be batched and genotyped every few weeks, depending on the rate of recruitment.  The 
investigators will periodically assess the genotype count of study completers to attempt to obtain equal 
numbers in each group.
Background, Significance and Rationale
Background, Significance and Rationale
It is estimated that worldwide there are over 75 million abusers of amphetamines and cocaine. Despite the 
public health significance of psychostimulant abuse, there remains no FDA-approved medication to 
facilitate treatment. Preclinical and clinical studies have provided data suggesting that naltrexone (NTX) 
may have potential for this indication (Jimenez-Gomez et al., 2010; Kim et al.,2001;  2009; Ray et al., 2012; 
Schad et al., 1995). However, a review of the literature reveals conflicting findings that require resolution. 
The introduction to genetic techniques to the study of drug abuse has helped to identify a number of 
genomic loci and variants that may moderate variability in treatment response (Anton et al., 2006; Arias et 


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al., 2014; Dahl et al,. 2006; David et al., 2007; Schacht et al, 2013).  A recent meta-analysis concluded that 
the OPRM1 A118G SNP (rs1799971) significantly moderates the treatment efficacy of NTX for alcohol 
abuse, increasing effectiveness by over 2 fold among G-allele carriers (AG/GG). The current study would 
be the first to investigate the moderating effect of this genotype in the efficacy of NTX to treat stimulant 
abuse. More specifically, we propose to investigate the interaction between NTX and intranasal (IN) 
methamphetamine (M-AMPH; 30mg/70kg), a commonly prescribed and abused amphetamine-type 
stimulant. In an exploratory endeavor, data from all participants  will be used to concurrently assess the 
ability of 5 functionally relevant genetic variants to predict NTX’s treatment efficacy [ANKK1 (rs1800497); 
DβH (rs1611115); OPRM1 (rs1799971); OPRM1 (rs6912029) (Haggkvist et al., 2009; Hendershot et al., 
2014) . This study therefore utilizes a focused approach to assess the influence of a genetic polymorphism 
whose influence has been substantiated by other investigations, and an exploratory approach to assess the 
individual and combined influence of several likely genetic moderators (Jayaram-Lindström et al. 2005; 
2008) .  These data may significantly advance individualized assessment and treatment of stimulant use 
disorder.
Specific Aims and Hypotheses
Specific Aims and Hypotheses
This investigation will seek to address the following specific aims:
• Primary Aim: Compare the ability of NTX to alter the subjective and reinforcing effects of IN M-AMPH 
between groups of OPRM1 A118G SNP carriers (AA vs AG/GG).
We hypothesize that G-allele carriers will report significant reductions in positive subjective and reinforcing 
effects following  active NTX pretreatment. In comparison, AA homozygous participants will report 
significantly less of an effect of NTX on these measures. 
• Exploratory Aim: Assess the association between various functionally relevant candidate genes and NTX 
treatment response. 
The presence or absence of one or more of the target genetic variants will be significantly associated with 
(and predict) change in the positive subjective and reinforcing effects of M-AMPH following 0 mg NTX 
and 50 mg NTX pretreatment.
Description of Subject Population
Sample #1
Specify subject population
Stimulant Users
Number of completers required to accomplish study aims
34
Projected number of subjects who will be enrolled to obtain required number of completers


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70
Age range of subject population
21-50
Gender, Racial and Ethnic Breakdown
Because the minor allele of the study’s primary target variant (A118G) is significantly less common among 
African-Americans (7%) than non-Hispanic Caucasians (28.7%) or Hispanics (27.8%)(Hastie et al., 2012), 
it will not be feasible to recruit an adequate number of participants of African ancestry to test the study’s 
primary hypothesis. Further, it is not feasible to combine African-ancestry and European-ancestry 
participants in the same analysis because to do so would result in confounding due to population genetic 
differences. Thus, we will enroll only participants who self-identify as White/Caucasian or as being of 
European ancestry. Of this sample, we anticipate that approximately 30% will self-identify as 
Hispanic/Latino. Based on previous experiences with recruiting stimulant abusers in the NYC area, we 
anticipate that 15% of our sample will be female. The investigators feel the anticipated ethnicity and sex 
enrollment figures reflect the population of amphetamine-type stimulant (ATS) users in New York 
City (NYC). The higher proportion of males reflects the nature of ATS abuse in this region, being 
primarily among gay males. The higher proportion of Hispanics is due to their higher representation 
within the NYC area.
Description of subject population
Participants will be individuals with mild-to-severe stimulant use disorder [specifically, 
amphetamine-type stimulants (ATS), including ecstasy] of Caucasian or of European descent, not 
seeking treatment for their drug abuse. 
Participants will be between the ages of 21 and 50, meeting the physical and mental health standards 
outlined in the Inclusion/Exclusion Criteria. 
Participants must have some experience with intranasal drug use.
Recruitment Procedures
Describe settings where recruitment will occur
Recruitment will primarily occur via print and online mediums. Potential participants who respond to ads 
will complete a brief phone screen and then are scheduled for complete screening at the New York State 
Psychiatric Institute (NYSPI).
How and by whom will subjects be approached and/or recruited? 
We will recruit non-treatment seeking stimulant users. Initial contact is made by the study's research 
assistants or volunteers who receive calls from potential participants who respond to the study's various 
advertising methods.
How will the study be advertised/publicized? 
Recruitment will be primarily through advertisements in local newspapers and online formats such as 
ResearchMatch and Study KiKs, along with app-based advertising.
Do you have ads/recruitment material requiring review at this time? 
Yes


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Does this study involve a clinical trial?
No
Concurrent Research Studies
Will subjects in this study participate in or be recruited from other studies? 
Yes
Describe concurrent research involvement
Potential participants may also be recruited from protocol# 7060 (PILOT STUDY: DYNAMIC 
CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING TO MEASURE BLOOD-BRAIN 
BARRIER PERMEABILITY, PI: Dr. Sandra Comer). This 9-day inpatient study also recruits recreational 
stimulant users to complete laboratory testing sessions where intranasal methamphetamine is administered. 
Potential participants' screening information may be shared between the two protocols. For example, if a 
participant  originally screens for study 7060, but their schedule does not accommodate the inpatient stay, 
they may be allowed to enroll in the current protocol, should they meet criteria. Completers from either 
study may also be transitioned directly into the other study, if their screening materials are still valid and 
show that they meet all criteria.
Inclusion/Exclusion Criteria
Name the subject group/sub sample
Stimulant Users
Create or insert table to describe the inclusion criteria and methods to ascertain them
1) Male or female age 21 to 50 years (self-report with ID verification).
 
2) DSM-5 criteria for mild-to-severe stimulant use disorder, along with intravenous, intranasal or 
smoked use of amphetamine-type stimulants in amounts equal to or greater than administered in the 
current study (Psychiatric Exam, MINI SCID).
 
3) Able to give written informed consent to participate (Physician's assessment). 
 
4) Females must be either post-menopausal, surgically sterilized, or using an acceptable method of 
contraception (double-barrier method like a condom with a spermicidal lubricant) to participate in this study 
(Clinical Interview, blood/urine pregnancy tests). 
 
5) Racially Caucasian or of European descent. (Self-Report /Investigator Assessment).
Create or insert table to describe the exclusion criteria and methods to ascertain them
1) Currently seeking treatment for a substance use disorder (Clinical Interview).
 


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2) DSM-5 criteria for moderate-to-severe substance use disorders (except those involving cocaine, 
amphetamines and nicotine) (Psychiatric Exam).
 
3) Psychiatric condition that may affect the participants' ability to provide informed consent (e.g., psychotic 
disorder), or make participation hazardous for the participant or study staff (e.g., severe 
depression/suicidality, or risk of violence) (Psychiatric Exam).
 
4) Uncontrolled neurological, cardiovascular, and hepatic diseases, active tuberculosis, or any other disorder 
that might make administration of study medications hazardous (Medical History/Physical Exam).
 
5) Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of 
study drug, or require medication or medical treatment (Medical History/ Physical Exam).
 
6) Current treatment with a psychotropic medication that in the physician's judgement would interfere with 
the study endpoints (Clinical Interview, Psychiatric Exam).
 
7) History of allergy, adverse reaction, or sensitivity to amphetamines (Clinical Interview).
 
8) Medical conditions that may make study participation hazardous [(Medical History, Physical 
Examination, Vital Signs, ECG, and laboratory tests (hematology, blood chemistry, urinalysis)].
History of seizures or cardiac risk conditions (unstable angina, cardiac arrhythmias, chest pain, 
strong palpitations (subjectively defined as the feeling that the heart is beating too hard, too fast, 
skipping a beat, or fluttering).
Elevated liver function tests (i.e., AST and ALT > 3 times the upper limit of normal).
Impaired renal function (creatinine > 1.2).
Hypertension (>140/90).
Pseudocholinesterase deficiency. 
Asthmatic symptoms within the past 3 years.
Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization) 
No
Waiver or alteration of consent
Yes
Waiver of documentation of consent 
No
Waiver of parental consent 


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No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol?
No
Describe procedures used to obtain consent during the screening process 
The participant's verbal consent is first obtained to complete the telephone screen (Research Assistant or 
Volunteer). Upon their first visit to NYSPI the participant is informed of the various screening procedures 
that determine eligibility for the study and sign a screening consent form (Study Nurse or Research 
Psychologist). Participants agree to provide a blood sample for genetic testing, as a part of the screening 
procedures. Upon this first visit, the study consent form is extensively  reviewed with the participant, 
however, the study consent form is only signed by the participant and physician once screening procedures 
are completed.
Describe Study Consent Procedures
We utilize a two-step consenting processing wherein the participant first signs the screening consent with a 
research psychologist or nurse. Once eligibility is determined, participants sign a study consent with a 
physician. The physician reviews the participant's screening chart, comparing it to the study's 
inclusion/exclusion criteria to ensure they are met. The physician assesses whether or not the participant is 
fully aware of the study procedures, risks and benefits, and then signs the consent form with the participant. 
Indicate which of the following are employed as a part of screening or main study consent procedures
   Consent Form
Justification for Waiver or Alteration of Consent
Waiver of consent is requested for the following
We are only requesting the Waiver of Documentation of Consent for the initial telephone interview during 
which verbal consent to answer questions is obtained. All other consent procedures are documented with the 
participant and staff signatures. Verbal consent to complete the telephone interview is first obtained the 
research assistant (for which the waiver of documentation authorization is requested). If the participant 
roughly meets study criteria, he or she is scheduled for an in-person screening. Once they arrive at NYSPI, 
participants sign a screening consent form which is explained to them by a research nurse, study investigator 
or division physician.
Explain why your research can not be practicably carried out without the waiver or alteration
 The waiver will allow us to better rule out significant numbers of individuals who are not eligible without 
wasting the time of critical staff like physicians and nurses
Describe whether and how subjects will be provided with additional pertinent information after participation
During the phone screen and upon the participants' first visit to NYSPI, the study procedures are described 
in detail.


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Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent
Brezing, Christina, MD
Comer, Sandra, PHD
Dakwar, Elias, MD
Evans, Elizabeth, MD
Jones, Jermaine, PHD
Luo, Sean, MD
Manubay, Jeanne, MD
Marino, Leslie, MD
Mogali, Shanthi, MD
MURRAY, JANET
Shulman, Matisyahu
Tindall, Claudia
Urban, Nina, MD
Vaezazizi, Leila
Williams, Arthur
Woolfolk, Vincent
Type in the name(s) not found in the above list
Study Procedures
Describe the procedures required for this study
Stimulant users will call the screening telephone number posted on newspaper ads, online ads, etc. and
complete the telephone interview (by study volunteers or research assistants) if they are interested in 
participating in the study. If the participant roughly meets study inclusion/exclusion criteria, he or she will 
be scheduled for an in-person screening. Once they arrive at NYSPI, participants will sign a screening 
consent form that will be explained to them by a research nurse or study investigator.
 
Screening procedures will include: Self-reported medical history and depression inventory,  measurements 
of height/weight and vital signs by a nurse or  bachelors-level research assistant, basic clinical labs 
(hematology, chemistry and urinalysis),  an electrocardiogram (ECG), and a clinical interview and Mini-
SCID by a PhD-Level research psychologist or Clinical Psychology PhD student. A physical and psychiatric 
examination will be conducted by a physician.  Medical oversight will be provided by Dr. Jeanne Manubay 
(Medical Director) and Shanthi Mogali, Division physician fellows will also be employed to be on call 
during lab sessions.
 
Study consent will be obtained from participants who pass the extensive medical and psychological 
screening, and testing sessions will be scheduled. Participants complete four lab sessions assessing the 
effects of pretreatment with 2 doses of NTX (0 and 50 mg; in random order) in combination with IN M-
AMPH (30mg/70 kg). 


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Sessions will be completed on an outpatient basis. The morning of the sample session (Day 1), participants 
will first complete a standard 11-panel urine drug screen and pregnancy tests. Both tests must be negative to 
proceed with the session. Exceptions may be made for marijuana positive urine tests at discretion of the 
investigators, if they feel the positive result is not due to recent (within 24 hrs) use. 
 
At  60 minutes prior to each session vital signs [blood pressure (BP), heart rate (HR), electrocardiogram 
(ECG)] will be assessed and participants will receive oral naltrexone or placebo.   ECG, HR, oxygen 
saturation, respiration rate and ETCO2 will be continuously monitored (Research Assistant). An automated 
Criticare System will measure BP every 5 minutes. All vitals will be recorded every 5 minutes.
 
At -30 minutes  participants will complete the pre-methamphetamine performance and subjective effects 
batteries, which will be subsequently assessed every 30 and 15 minutes after drug administration, 
respectively. Intranasal methamphetamine (M-AMPH) is administered at time 0 (by Physician), with sample 
session assessments continuing for 3 hours post drug administration (See Schedule of Events). Drug 
subjective effects will be assessed using  a  computerized 26-item visual analog questionnaire (VAS) and 
the Drug-Effect Questionnaire (DEQ), along with the Sexual Probability Discounting Task/Sex Value 
Assessment Task (assessment of delay discounting of condom-protected sex, only at screening and 1 hour 
after M-AMPH administration). Performance tasks include the digit-symbol substitution task (DSST), 
designed to assess changes in visuospatial processing; and the divided attention task (DAT), designed to 
assess changes in vigilance and inhibitory control. Following successful completion of a field sobriety test, 
participants are sent to their home address in a taxi or car service.
 
Participants will return the next day to complete the choice or self-administration session (Day 2). 
Participants complete a 60-minute, 10-trial self-administration procedure where at each trial they are given 
the option to choose between 1/10th of the sample drug or 1/10th of the alternative monetary reinforcer $15. 
The response requirements to choose drug or money increases independently as follows: 50, 100, 200, 400, 
800, 1200, 1600, 2000, 2400, and 2800 responses. In order to receive 100% of either reinforcer, a 
participant will have to select that reinforcer on all 10 trials and make a total of 11,550 responses. Following 
completion of the task, participants received the chosen amount of drug and/or money. Participants'  vitals 
will be monitored for 3 hours post drug administration. Following successful completion of a field sobriety 
test, participants are sent to their home address in a taxi or car service. The effects of NTX pretreatment on 
the rewarding and reinforcing effects of M-AMPH (% shift between active and placebo) will be compared 
between the two A118G genotypes (AA vs AG/GG) to address the study's primary aim. 
 
Subjects who finish both arms of the study will complete a total of 4 lab sessions Sample (Day 1) and 
Choice (Day 2): 0 mg NTX + M-AMPH &  Sample (Day 1) and Choice (Day 2): 50 mg NTX + M+AMPH 
.  Each of the 4 lab sessions will take approximately 4 hours to complete (See Testing Schedule).
 
The two arms of the study will be completed at least 72 hrs apart. The time between the two arms should 
allow for the clearance of the study drug from the urine. However, participants who are amphetamine 
positive the day of the second set of lab sessions may proceed with the session, if after meeting with the 
investigator, (s)he feels that no other acute amphetamine use is responsible for the positive result. 
 
 


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One month after the discharge, participants will be asked to return to the laboratory for a follow-up 
evaluation. At this time, participants will be asked about drug use since discharge and will provide a urine 
sample to test for drugs of abuse.
 
You can upload charts or diagrams if any
Schedule of events.pdf
Testing schedule.pdf
Criteria for Early Discontinuation  
Criteria for Early Discontinuation
Participants will be withdrawn from the study if they: 1) do not comply with division policies or study 
procedures, 2) are deemed medically at risk for further study participation based upon Criteria for 
Terminating a Session (detailed below), 3) express a desire to receive treatment for their drug use. All 
participants who are withdrawn from the study will be offered referrals for appropriate medical treatment 
with their primary care physician and/or treatment for substance use. Treatment studies ongoing at 
Substance Use Treatment and Research Service (STARS) will be described and the participant will be given 
a list of inpatient and outpatient treatment services in the New York City area.
 
Criteria for Terminating a Session: The occurrence of any of the following abnormalities in a participant’s 
vital signs will result in the immediate ending of a laboratory session: (a) Systolic blood pressure > 180 mm 
Hg, sustained for longer than 6 minutes (> 3 consecutive readings), (b) diastolic blood pressure > 100 mm 
Hg, sustained for longer than 6 minutes (> 3 consecutive readings),  (c) heart rate > (220 – subject age x 
0.85) bpm, sustained for longer than 6 minutes (> 3 consecutive readings), and (d) significant ECG 
abnormality (e.g., >10 PVC's/hr, or multifocal PVS's, or significant ST changes, chest pain), or 
seizure are observed.
Blood and other Biological Samples
Please create or insert a table describing the proposed collection of blood or other biological specimens
During screening a 30cc venous blood sample will be collected for medical evaluation. Another 30cc 
sample will be used to obtain DNA for genetic testing (60 cc in total). 
 
As an NIH-funded genetics study, whole blood samples may be used to make a cell line to create a source of 
DNA for storage in a repository for future research. If participants consent to their sample being used in 
future research, their DNA may be available to researchers indefinitely.  For the purposes of the current 
study, DNA information will be kept for a maximum of 5 years.
 
 


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Assessment Instruments
Create a table or give a brief description of the instruments that will be used for assessment
Screening:
Medical History Questionnaire 
Clinical Interview/Substance Use Inventory  (Research Psychologist)
MINI SCID (Research Psychologist) 
Physical/Psychiatric Exam (Physician)
Beck's Depression Inventory 
Basic Clinical Labs (Hematology, Chemistry and Urinalysis) 
Electrocardiogram (ECG)
CD-RISC-25 (Resilience Scale)
Sexual Probability Discounting Task/Sex Value Assessment Task
 
Lab Session:
Visual Analog Scale (VAS) assessment of drug effects
Drug Effects Questionnaire (DEQ)
Progressive Ratio drug self-administration 
Sexual Probability Discounting Task/Sex Value Assessment Task
Digit Symbol Substitution Task (DSST)
Divided Attention Task (DAT)
Please attach copies, unless standard instruments are used
Substance Use Inventory.pdf
MEDICAL HISTORY QUESTIONNAIRE.pdf
BDI.pdf
SCID.pdf
Off label and investigational use of drugs/devices
Choose from the following that will be applicable to your study 
   Drug
Select the number of drugs used in this study
2
Drug #1
Name of the drug 
methamphetamine
Manufacturer and other information


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Methamphetamine for human use will be obtained from NIDA via the Research Triangle Institute.
Approval Status
IND is approved
IND#
133276
Who holds the IND/IND sponsor?
Other
Enter Name
Jermaine Jones
Drug #2
Name of the drug
Naltrexone Hydrochloride
Manufacturer and other information
Commercially available naltrexone will be purchased from Cardinal Health.
Approval Status
IND is approved
IND#
133276
Who holds the IND/IND sponsor?
Other
Enter Name
Jermaine Jones
Research Related Delay to Treatment
Will research procedures result in a delay to treatment?
No
Treatment to be provided at the end of the study
Although this study will only recruit individuals not seeking treatment, on the last day of the study 
participants will receive information about different treatment options for drug abuse including: medication 
trials at STARS, along with inpatient and outpatient behavioral therapy.
Clinical Treatment Alternatives
Clinical treatment alternatives
This is not a treatment study. However, counseling about different treatment options and referrals for 
treatment are available to participants at any time, before, during, or after their participation in this study. 
Participants will also be informed that they do not have to participate in this study in order to get a referral 
to help stop using drugs.


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Risks/Discomforts/Inconveniences 
Risks that could be encountered during the study period
Blood Drawing: During the screening assessments, 30 cc venous blood samples will be collected for 
medical evaluation. For subject who qualify for the study another 30 cc will be collected for genetic testing 
(60 cc total). Blood drawing may cause mild discomfort at the site where the needle is inserted, and it poses 
a small risk of bruising at the site as well as an extremely low risk of infection.
 
Psychological Distress: The structured interviews, rating scales, and questionnaires should add no physical 
risk. However, because many of the interviews and assessments are time consuming to complete and 
involve topics of a sensitive nature, some people have found them to be physically or emotionally tiring. 
Patients are informed prior to study entry that they can refuse to answer any questions and that they can 
request to stop at any time. If a participant becomes agitated during any of the interviews or assessments, he 
or she will be provided with therapeutic assistance.
 
Methamphetamine Administration: The major risks of intranasal M-AMPH administration are increased 
blood pressure and heart rate. Other side effects include excitation, restlessness, dizziness, insomnia, 
euphoria, dysphoria, tremor, headache, dry mouth, diarrhea, constipation, and weight loss. Less common 
side effects include seizures, blurred vision, increased thought disorders, psychosis, and hallucinations. Our 
Division has safely administered psychoactive stimulants including cocaine, amphetamine and 
methamphetamine via oral, smoked, intravenous and intranasal routes in numerous studies without 
significant medical complications (Comer et al., 1996, 2001, 2013; Collins et al., 2007; Hart et al., 2001, 
2008; Foltin and Haney., 2004: Kirkpatrick et al., 2012). 
 
Naltrexone Administration: Naltrexone may mildly impair the functioning of the liver. This effect on the 
liver typically resolves after naltrexone is discontinued. Naltrexone may also cause stomach upset, nausea, 
and vomiting. In addition, administration of naltrexone may increase blood sugar levels, which may produce 
symptoms such as dizziness, increased breathing, dehydration, sedation, and localized seizures. Naltrexone 
administration may also induce opioid withdrawal symptoms in an opioid-dependent participant. Although 
this risk is unlikely as regular opioid use would exclude screening subjects.  
 
Subsequent Drug Use: The possibility of study participants increasing their drug use as a result of their 
participation in the proposed study is small. Previous studies have shown that administration of drugs of 
abuse to drug-abusing volunteers does not lead to increased drug use after study participation: 
• Bigelow GE, Brooner RK, Walsh SL, Preston KL, Liebson IA. (1995) Community outcomes following 
research exposure to cocaine or opioids. In: IHL, editor. Problems of Drug Dependence 1994: Proceedings 
of the 56th Annual Scientific Meeting. Washington DC: NIH; p. 354.
• Elman I, Krause S, Karlsgodt K, Schoenfeld DA, Gollub RL, Breiter HC, et al. (2001) Clinical outcomes 
following cocaine infusion in nontreatment-seeking individuals with cocaine dependence. Biol Psychiatry 
49: 553–555.
• Fischman MW, Schuster CR, Resnekov L, Shick JF, Krasnegor NA, Fennell W (1976) Cardiovascular and 
subjective effects of intravenous cocaine administration in humans. Arch Gen Psychiatry 33: 983–989.
• Pratt WM, Davidson D. (2005) Does participation in an alcohol administration study increase risk for 
excessive drinking? Alcohol 37: 135–141.


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Jones, Jermaine
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Analysis of our own 1 month follow-up data across 5 studies where opioids were administered found that 
participation decreases drug use and facilitates entry into treatment. More specifically, 42% of our study 
completers were not using heroin 1 month after study completion and 55% decreased their heroin use from 
5.9 bags per day at baseline to 2.9 bags per day at the 1-month follow up visit. In addition, 21% initiated 
buprenorphine or methadone treatment, 6% enrolled in a detox program, and 25% were referred to treatment 
(Roux et al., 2012). A similar follow-up analysis of studies where cocaine was administered yielded similar 
results. Cocaine use significantly decreased at 1 month (-$165.13/week) and 3 months (-$118.59/week) after 
study participation. This decrease was not accompanied by a change in other drug use, e.g., a compensatory 
increase in alcohol, marijuana or nicotine use (Kalapatapu et al., 2012).
Pregnancy: Female participants must not be pregnant to be included in the study. Urine pregnancy tests are 
performed at each screening visit and immediately prior to each lab session.
 
Confidentiality: Potential participants divulge information that is sensitive and may have adverse social 
consequences if released. This would include information released to insurance companies, health care 
agencies, or family members, or information made public in any way. A Certificate of Confidentiality will 
be obtained for the current study and procedures for protecting confidentiality of records will be followed. 
Specifically, all data records containing identifying information will be kept in locked files and on 
password-protected computers. Blood samples for genetic testing will be sent only with participant code 
numbers, with no potentially identifying information. Only the study investigators will have access to the 
codes linking the participant to their identifying information. The contract agencies performing these genetic 
tests will not have access to the subjects’ identifying information. Only the primary investigator and other 
core study staff will have access to identifiable information, which will be maintained on site under lock and 
key. All computer data are stored without names or other uncoded identification. Patients will be identified 
only through a numerical code in all electronic databases. 
 
Genomic Information: Participants will be notified that these samples will be used for an investigation into 
the association between drug abuse and genotype, and that these samples will be archived for future 
investigations. Participants will also be informed of the Genetic Information Nondiscrimination Act (GINA) 
that generally makes it illegal for health insurance companies, group health plans, and most employers to 
discriminate based upon genetic information.
Describe procedures for minimizing risks
Screening: An extensive battery of screening tests, including psychometric evaluations, interview 
assessments, and a medical examination in order to provide as much information as possible upon which to 
base participant selection.The exclusionary criteria are designed to minimize the risks to participants. The 
evaluating study physician or Principal Investigator reviews all medical assessments along with medical 
history to determine if any would make study procedures hazardous.
 
Participant Education: All participants will be informed of the possible side effects and risks mentioned 
above, which will also be included in an informed consent document. For eligible participants, the study PI 
and research psychiatrist will describe the study in detail including study procedures, and possible risks and 


Protocol Summary Form
7347
Jones, Jermaine
Page 16 of 20
benefits of participation. Participants may sign the consent form only after reading it, having any questions 
answered, and being given a copy to keep.
 
Consent Procedures: Participants will provide informed consent to screening and all study procedures prior 
to testing. Participants are instructed to call us if any untoward effects occur after the laboratory session and 
are given an emergency contact number.
Methods to Protect Confidentiality
Describe methods to protect confidentiality
We deal with issues of confidentiality by using coded records, store signed consent forms in a locked safe, 
and try to the best of our ability to maintain confidentiality. Electronic data are stored on computers that are 
password protected. We will obtain a Certificate of Confidentiality for this project. We also point out to 
prospective participants that we cannot assure that their drug histories and other personal records might not 
become known. Those who are hospitalized have hospital charts and we cannot guarantee the confidentiality 
of these charts. Participants in other studies have understood these procedures and have agreed to participate 
under these conditions.
Will the study be conducted under a certificate of confidentiality?
Yes, we will apply for the Certificate of Confidentiality
Direct Benefits to Subjects  
Direct Benefits to Subjects
There are no direct benefits to the participants.
Compensation and/or Reimbursement 
Will compensation or reimbursement for expenses be offered to subjects?
Yes
Please describe and indicate total amount and schedule of payment(s). 
Include justification for compensation amounts and indicate if there are bonus payments.
Participants will receive $50 for each screening visit, for up to 4 visits. This money will be paid at the end of 
each day.
Participants will  receive $125 for each of the 4 completed lab sessions. Additional money can be earned 
during experimental sessions. 
 
Participants will also be compensated $25 for any unscheduled visits for repeat laboratory/screenings tests 
and $50 for the 30-day follow-up visit. 
 


Protocol Summary Form
7347
Jones, Jermaine
Page 17 of 20
Total payments will be between $650-$800. 
 
References
References
Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, 
Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, 
Swift R, Weiss RD, Williams LD, Zweben A (2006) Combined pharmacotherapies and behavioral 
interventions for alcohol dependence: the COMBINE study. A randomized controlled trial. JAMA 295: 
2003-2017.
Arias AJ, Gelernter J, Gueorguieva R, Ralevski E, Petrakis IL. (2014) Pharmacogenetics of naltrexone and 
disulfiram in alcohol dependent, dually diagnosed veterans. Am J Addict 23: 288-293.
 
Bigelow GE, Brooner RK, Walsh SL, Preston KL, Liebson IA. (1995) Community outcomes following 
research exposure to cocaine or opioids. In: IHL, editor. Problems of Drug Dependence 1994: Proceedings 
of the 56th Annual Scientific Meeting. Washington DC: NIH; p. 354.
Bujarski S, MacKillop J, Ray LA. (2012) Understanding naltrexone mechanism of action and 
pharmacogenetics in Asian Americans via behavioral economics: A preliminary study. Exp Clin 
Psychopharmacol 20: 181-190.
Collins SL, Evans SM, Foltin RW, Haney M. (2007) Intranasal cocaine in humans: effects of sex and 
menstrual cycle.Pharmacol Biochem Behav. 86(1):117-24.
 
Comer SD, Hart CL, Ward AS, Haney M, Foltin RW, Fischman MW (2001). Effects of repeated oral 
methamphetamine administration in humans. Psychopharmac
ology 155: 397–404.
Comer SD, Haney M, Foltin RW, Fischman MW. (1996) Amphetamine self-administration by humans: 
modulation by contingencies associated with task performance. Psychopharmacology (Berl). 127: 39-46.
 
Comer SD, Mogali S, Saccone PA, Askalsky P, Martinez D, Walker EA, Jones JD, Vosburg SK, Cooper 
ZD, Roux P, Sullivan MA, Manubay JM, Rubin E, Pines A, Berkower EL, Haney M, Foltin RW.2013 
Effects of acute oral naltrexone on the subjective and physiological effects of oral D-amphetamine and 
smoked cocaine in cocaine abusers. Neuropsychopharmacology 38: 2427-2438.
 
Dahl JP, Jepson C, Levenson R, Wiley EP, Patterson F, Berrettini WH, Lerman C. (2006) Interaction 
between variation in the D2 dopamine receptor (DRD2) and the neuronal calcium sensor-1 (FREQ) genes in 
predicting response to nicotine replacement therapy for tobacco dependence. Pharmacogenomics J 6: 194-
199. 


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David SP, Brown RA, Papandonatos GD, Kahler CW, Lloyd-Richardson EE, Munafo MR, Shields PG, 
Lerman C, Strong D, McCaffery J, Niaura R. (2007) Pharmacogenetic clinical trial of sustained-release 
bupropion for smoking cessation. Nicotine Tob Res 9: 821-833.
 
Elman I, Krause S, Karlsgodt K, Schoenfeld DA, Gollub RL, Breiter HC, et al. (2001) Clinical outcomes 
following cocaine infusion in nontreatment-seeking individuals with cocaine dependence. Biol Psychiatry 
49: 553–555.
 
Fischman MW, Schuster CR, Resnekov L, Shick JF, Krasnegor NA, Fennell W (1976) Cardiovascular and 
subjective effects of intravenous cocaine administration in humans. Arch Gen Psychiatry 33: 983–989.
 
 
Foltin RW, Haney M. (2004) Intranasal cocaine in humans: acute tolerance, cardiovascular and subjective 
effects. Pharmacol Biochem Behav. 78(1):93-101.
.
Haggkvist J, Londholm S, Franck J. (2009) The opioid antagonist naltrexone attenuates reinstatement of 
amphetamine drug-seeking in the rat. Behav Brain Res 197: 219–224.
Hart CL, Gunderson EW, Perez A, Kirkpatrick MG, Thurmond A, Comer SD, et al., (2008) Acute 
physiological and behavioral effects of intranasal methamphetamine in humans. 
Neuropsychopharmacology. 33:1847–1855.
Hart CL, Ward AS, Haney M, Foltin RW, Fischman MW. (2001) Methamphetamine self-administration by 
humans. Psychopharmacology. 157:75–81.
Hastie BA1, Riley JL 3rd, Kaplan L, Herrera DG, Campbell CM, Virtusio K, Mogil JS, Wallace MR, 
Fillingim RB. (2012) Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity. Pain 153: 
1610-1619.
Jayaram-Lindström N,Wennberg P, Beck O, Franck J. (2005) An open clinical trial of naltrexone for 
amphetamine dependence: compliance and tolerability. Nord J Psychiatry 59:167-171.
Jayaram-Lindström N, Konstenius M, Eksborg S, Beck O, Hammarberg A, Franck J. (2008) Naltrexone 
attenuates the subjective effects of amphetamine in patients with amphetamine dependence. 
Neuropsychopharmacol 33: 1856-1863.
 
Jayaram-Lindström N, Hammarberg A, Beck O, Franck J. (2008) Naltrexone for the treatment of 
amphetamine dependence: a randomized, placebo-controlled trial. Am J Psychiatry 165: 1442-1448.
Jimenez-Gomez C, Winger G, Dean RL, Deaver DR, Woods JH. (2010) Naltrexone decreases D-
amphetamine and ethanol self-administration in rhesus monkeys. Behav Pharmacol 22: 87–90. 
Kalapatapu RK et al., (2012) Substance use after participation in laboratory studies involving smoked 
cocaine self-administration. Drug Alcohol Depend 120(1-3): 162-167.
 


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Kim SW, Grant JE, Adson DE, Shin YC. (2001) Double-blind naltrexone and placebo comparison study in 
the treatment of pathological gambling. Biol Psychiatry 49: 914–921.
Kirkpatrick MG, Gunderson EW, Johanson CE, Levin FR, Foltin RW, Hart CL. (2012) Comparison of 
intranasal methamphetamine and d-amphetamine self-administration by humans. Addiction. 107(4): 783-91.
Marks KR, Lile JA, Stoops WW, Rush CR. (2014) Separate and combined impact of acute naltrexone and 
alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users. 
Psychopharmacology (Berl) 231: 2741-2750. 
Pratt WM, Davidson D. (2005) Does participation in an alcohol administration study increase risk for 
excessive drinking? Alcohol 37: 135–141.
 
Ray LA, Bujarski S, Chin PF, Miotto K. (2012) Pharmacogenetics of naltrexone in Asian-Americans: a 
randomized placebo-controlled laboratory study. Neuropsychopharmacol 37: 445-455.
 
Roux et al., (2012) Impact of inpatient research participation on subsequent drug use patterns: implications 
for ethics and public health. Addiction 107: 642-649.
 
Schad CA, Justice JB, Holtzman SG. (1995) Naloxone reduces the neurochemical
and behavioral effects of amphetamine but not those of cocaine. Eur J Pharm 275: 9-16.
Schacht JP, Anton RF, Voronin KE, Randall PK, Li X, Henderson S, Myrick H. (2013) Interacting effects 
of naltrexone and OPRM1 and DAT1 variation on the neural response to alcohol cues. 
Neuropsychopharmacol 38: 414-422.
Uploads
Upload the entire grant application(s)
R21-DA040225-01A1 Full application.pdf
Upload copy(ies) of unbolded Consent Form(s)
Screening CF 11-11-16.pdf
Study CF NaltrexoneAmphetamine 12-13-16.pdf
Upload copy(ies) of bolded Consent Form(s)
Screening CF 11-11-16 (Bold).pdf
Study CF NaltrexoneAmphetamine 12-13-16 (Bold).pdf
Upload copy(ies) of recruitment materials/ads to be reviewed
Ads 11-4.pdf
Upload evidence of FDA IND approval(s)
Acknowledge IND (COR-INDACK-01) (3).pdf - Adobe Acrobat Pro.pdf
FDA Correspondence.pdf
Letter of Authorization Comer.pdf
IND 133276 Study May Proceed.pdf
Upload copy(ies) of the HIPAA form


Protocol Summary Form
7347
Jones, Jermaine
Page 20 of 20
HIPAA 2016 9-16.pdf
Upload any additional documents that may be related to this study
HIPAA Waiver.pdf
7347_Changes_approval-1.pdf
IND_Form 1-3-17.pdf


 
RESEARCH VOLUNTEERS  
Have you used Meth or Ecstasy before? Caucasian or Latino men and women, aged 21-50 
yrs needed for a research study at the NY State Psychiatric Institute. Earn up to $800. Call 
the Substance Use Research Center at (646) 774-6243.  
 
 
RESEARCH VOLUNTEERS  
Have you smoked or snorted amphetamines before? Caucasian or Latino men and women, 
aged 21-50 yrs needed for a research study at the NY State Psychiatric Institute. Earn up to 
$800. Call the Substance Use Research Center at (646) 774-6243.  
 
Do you use Crystal?  
The Substance Use Research Center at the NY State Psychiatric Institute seeks healthy, 
Caucasian or Latino Meth or Ecstasy users, between the ages of 21-50, for a research 
study evaluating stimulant effects. You can earn up to $800. For more information, call 
(646) 774-6243.  
 
Do you use Meth?  
The Substance Use Research Center at the NY State Psychiatric Institute seeks healthy, 
Caucasian or Latino Meth or Ecstasy users, between the ages of 21-50, for a research 
study evaluating stimulant effects. You can earn up to $800. For more information, call 
(646) 774-6243. 
Do you use Ecstasy?  
The Substance Use Research Center at the NY State Psychiatric Institute seeks healthy, 
Caucasian or Latino Meth or Ecstasy users, between the ages of 21-50, for a research 
study evaluating stimulant effects. You can earn up to $800. For more information, call 
(646) 774-6243.  
 
Do you Party?  
The Substance Use Research Center at the NY State Psychiatric Institute seeks healthy, 
Caucasian or Latino Meth or Ecstasy, users between the ages of 21-50, for a research 
study evaluating stimulant effects. You can earn up to $800. For more information, call 
(646) 774-6243. 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
1
 
Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse 
Screening Consent Summary Form 
 
 
Purpose of Study  
The goal of this research study is to collect information on the effects of amphetamine-type drugs, how 
they interact with the medication naltrexone, and how genetics may alter this interaction.  Genetics is 
the study of how genes control characteristics like your hair and eye color. Just as differences in our 
genetic code help explain why we all look different, these differences can also help to explain why some 
medications are effective for some people but not for others. 
 
You are being asked to screen for this study as a stimulant user. By participating, you will help 
researchers meet the goals of the study. This study is being funded by the National Institute on Drug 
Abuse. Dr. Jermaine Jones is the principal investigator and the person in charge of the study. All 
screening and study procedures will be conducted at the New York State Psychiatric Institute (NYSPI).  
 
Participation in this screening is voluntary. If you decide not to participate, or if you later decide to stop 
participating, you will not lose any benefits to which you are otherwise entitled. A decision not to 
participate or withdraw your participation will not affect your current or future treatment at the New York  
State Psychiatric Institute. This is not a treatment study. Information is being collected for research 
purposes. Referrals for treatment are available at any time. You do not have to participate in this study in 
order to get a referral to help stop taking drugs. If you are interested in treatment, an appropriate 
treatment referral will be arranged.  
 
 
Study Procedures  
You have been selected as a potential research volunteer. In order to participate in the study, you must  
first pass medical and psychiatric screening. This will include answering a general health questionnaire  
and other questionnaires relating to drug use; receiving an interview by a psychologist; and a physical 
examination. An electrocardiogram will be done to check the functioning of your heart. Blood samples 
are also collected to assess your general physical health, and urine samples are collected to test for 
drugs of abuse as well as pregnancy. If you are a woman, you will be given a pregnancy test. If you think 
you might be pregnant, please tell the investigator. You will be given another pregnancy test before each 
testing session, and if it is positive you will not be eligible to participate.  Additionally, this study has a 
genetic component that requires the collection of a blood sample to extract DNA (described in detail in 
the Study Consent form). The cells of your body contain a molecule called deoxyribonucleic acid, or DNA 
for short.  DNA is passed down from your parents and carries a code, in the form of genes, which 
determines your physical characteristics, such as the color of your hair and eyes. 
 
If you are still eligible after the screening, the study will be described to you in detail and you will be given 
a detailed Study Consent form outlining all aspects of the study.  
 
 
Risks  
During blood drawing, there is a risk of slight discomfort and/or bruising at the site where the needle is 
inserted. Approximately 2 tablespoons will be taken for health testing. If you qualify for the study, another 
2 tablespoons will be collected for genetic testing (4 total tablespoons). When someone donates blood, 
32 tablespoons are taken on one occasion.  
 
The structured interviews and questionnaires are time consuming to complete and involve topics of a 
sensitive nature.  
 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
2
As in any research study, it is possible that personal information about you could become known to other 
people. The investigators will take precautions to prevent this from happening. Your name will not appear 
on any questionnaires or tests that you complete during the study. Instead, all questionnaires and tests 
you complete will be coded with a study code number. The results from your individual genetic analyses 
will be kept confidential as described above.  
 
Benefits  
You are not expected to benefit directly from participation in this study. However, research studies such 
as this one may help scientists investigating risk factors for drug abuse, and in the development of 
treatment medications. 
 
Confidentiality  
We have applied for a Certificate of Confidentiality issued by the National Institutes on Drug 
Abuse (NIDA). With this Certificate, the researchers cannot be forced to release any research data 
in which you are identified, even under a court order or subpoena, without your written consent. 
The Certificate does not prevent the researchers from reporting suspected or known neglect or 
sexual or physical abuse of a child, or threatened violence to self or others. Such information will 
be reported to the appropriate authorities.  
 
You should understand that a Certificate of Confidentiality does not prevent you or a member of 
your family from voluntarily releasing information about yourself or your involvement in this 
research.  If an insurer, employer, or other person obtains your written consent to receive 
research information, then the researchers may not use the Certificate to withhold that 
information. 
 
Records will only be available to research staff and to Federal, State and Institutional regulatory 
personnel (who may review records as part of routine audits). Your name and other personal identifying 
information will be stored in an electronically secure database at New York Psychiatric Institute. 
Electronic information is also coded and is stored on computers that are password protected. Signed 
consent forms and other forms containing identifying information will be kept in a locked file, and all 
interviews, assessments, etc. will be coded with initials and numbers.  
 
Compensation  
As a result of participating in this screening you will receive $50 per screening visit, to a maximum of four 
visits. If you are enrolled in the study and complete all study procedures, you will earn between $650 and 
$800.   
 
In Case of Injury  
Federal regulations require that we inform participants about our institution's policy with regard to 
compensation and payment for treatment of research-related injuries. If you believe that you have 
sustained an injury as a result of participating in a research study, you may contact the Principal 
Investigator at (646) 774-6113 so that you can review the matter and identify the medical resources that 
may be available to you 
  
Questions  
The investigators will answer to the best of his ability any questions that you may have now or in the 
future about the research procedures. You may contact the Principal Investigator, Dr. Jermaine Jones, 
who can be reached at (646) 774-6113, if you have any questions. You will be given a copy of this 
consent form to take home with you. If you have any questions about your rights as a research 
participant, want to provide feedback, or have a complaint, you may call the NYSPI Institutional Review 
Board (IRB). An IRB is a committee that protects the rights of human subjects in research studies. You 
may call the IRB Main Office at (646) 774-7155 during regular office hours. 
 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
3
 
Documentation of Consent 
 
 
 
I voluntarily agree to participate in the research study described above.  
 
 
Name of Participant__________________________________  
 
 
Signature of Participant_______________________________ Date_______________  
 
 
 
 
 
Investigator, Physician, or Nurse 
 
Printed Name__________________________________  
 
 
Signature______________________________________Date________________  


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
1
 
Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse 
 
Consent Summary Form  
 
Below is a summary of the study in which you are being asked to participate.  This outline is meant to be 
a guide for you to use while considering the study and reading the consent form. It is not meant to 
replace the consent form you will need to sign if you decide to participate in the study.  The consent form 
contains much more detailed information about the study and the risks you will need to consider in 
making your decision. 
 
 
You are being asked to participate in a research study that is attempting to collect information on 
the effects of an amphetamine drug, if they can be blocked by another medication, and how your 
genetics plays a role. Genetics is the study of how genes control characteristics like your hair and 
eye color. Just as differences in our genetic code help explain why we all look different, these 
differences can also help to explain why some medications are effective for some people but not 
for others. 
 
 
You will complete 4 laboratory sessions. During 2 of these sessions an amphetamine drug will be 
administered intranasally, along with an oral dose of the medication naltrexone.  During the other 
2 sessions you will have the opportunity to work for the drug or money by making finger presses 
on a computer mouse.  
 
Each laboratory session is about 4 hours long. 
 
 
Like all research, your decision to participate is up to you; taking part is voluntary. 
 
Risks of Study Participation: 
 
 
If you decide to participate in this study, there are possible side effects and potential risks you 
should know about, and these are detailed in the consent form.  
 
 
The major risk of study participation is related to amphetamine administration. There have been 
reports of death and potentially a heart attack associated with amphetamine use. On rare 
occasions amphetamine use has been associated with chest pain, temporary hallucinations 
(seeing and hearing things that were not present), disorientation, seizures and muscle stiffness. 
You may also experience: excitation, restlessness, anxiety, headache, dry mouth, diarrhea, 
constipation, rapid pulse, loss of appetite, fluttering of the heart, irregular heart beats, and 
occasionally nausea, dizziness, sedation, or tremors. 
 
Benefits 
This study is not designed to benefit you directly. The genetic results will not be available to you or 
your doctors. However, research studies such as this one may help scientists investigating risk 
factors for drug abuse, and in the development of treatment medications. 
 
Compensation 
You will be compensated for your time and effort. As in all research, it is your choice to participate in 
this study and you do not have to participate if you do not want to. Also, you may stop participating at 
any time.  Please read the Consent Form carefully and ask the study physician any questions or 
concerns you might have. 
 
You can contact Dr. Jermaine Jones at (646) 774-6113 with any questions. 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
2
 Consent Form  
 
Study Purpose: The goal of this research study is to collect information on the effects of amphetamine 
type drugs and how they interact with the medication naltrexone. As a part of this study we will look at 
differences in people’s DNA in an attempt to try to understand differences in how people respond to 
drugs. The cells of your body contain a molecule called deoxyribonucleic acid, or DNA for short.  DNA is 
passed down from your parents and carries a code, in the form of genes, which determines your physical 
characteristics, such as the color of your hair and eyes; and risk for some diseases. Just as differences 
in our genetic code help explain why we all look different, these differences can also help to explain why 
some medications are effective for some people but not for others.   
 
You are being asked to participate because you have some history of use of amphetamine drugs or other 
stimulants. By participating, you will help researchers meet the goals of the study. This study is being 
funded by the National Institute on Drug Abuse. Dr. Jermaine Jones is the principal investigator and the 
person in charge of the study. Study procedures will be conducted at the New York State Psychiatric 
Institute (NYSPI).  
 
Details about this study are discussed below. It is important that you understand this information so that 
you can decide if you want to be in this research study. You will be given a copy of this consent form. 
You should ask the researchers, or staff members who may assist them, any questions you have about 
this study at any time. This consent form may contain words that you do not understand. Please ask the 
study doctor or the staff to explain any words or information that you do not understand. You may take 
home an unsigned copy of this consent form to think about or discuss with your family or friends before 
making your decision to participate in the study.  
 
The study will enroll up to 70 people at NYSPI.  
 
Voluntary: Participation in this research study is voluntary. If you decide not to participate, or if you later 
decide to stop participating, you will not lose any benefits to which you are otherwise entitled. A decision 
not to participate or to withdraw your participation will not affect your current or future treatment at the 
New York State Psychiatric Institute.   
 
 
Alternative Treatments/Alternatives to Participation: This is not a treatment study. Information is 
being collected for research purposes only. The alternative to participating would be not to participate. 
Referrals will be given to you at the end of the study if you are interested in treatment for your drug use. 
This genetic study is intended to learn about treating drug abuse and not about you.  We will not be 
providing you with any information about your DNA or your risk for developing inherited illnesses. 
 
 
Study Procedures: If you decide to participate you will undergo the following procedures: 
 
You will participate in a total 4 laboratory sessions. On the morning of each laboratory session a urine 
sample will be collected to test for recent drug use, and for pregnancy (in women). If either test is positive 
you will not be eligible to participate. Each laboratory session will take approximately 4 hours to 
complete. On Day 1 you will receive an intranasal amphetamine drug and an oral drug prior to it. The oral 
drug will be an FDA-approved opioid receptor blocker (naltrexone) or placebo (sham medication without 
any effects). Whether you get naltrexone or placebo will be randomly determined (like flipping a coin), 
and you will not be told which one you get that day. For the next 3 hours after these drugs are given, you 
will be asked to answer questions on the computer about how the drug makes you feel (such as “I feel 
high” or “I feel a good drug effect”) and the way you might behave in pretend situations involving sex. At 
the end of the session, you will complete a field sobriety test. If you are not too high or intoxicated, we 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
3
will call a car service or taxi to take you to your home address. If medical staff feels you are overly 
intoxicated, you will be asked to wait with us until we feel it’s safe for you to leave.   
 
On the following day (Day 2) you will return to NYSPI and have the opportunity to work for the intranasal 
drug by making finger presses on a computer mouse. Like at the end of Day 1, you will be asked to 
complete a field sobriety test before leaving NYSPI.  You will repeat these two sessions (Day 1 & 2) 
again at least 3 days apart. For safety, we will monitor your heart rate, blood pressure and electrical 
activity of the heart throughout both sessions.    
 
 
We will ask for you to return about thirty days after your last session to complete a brief follow-up visit.  
 
Genetic Information: As a part of this study DNA samples are collected using 2 tablespoons of your 
blood. The purpose of this part of the research study is to look at differences in people’s DNA in an 
attempt to try to understand differences in how people respond to drugs.  Whole blood samples can be 
used to make a cell line (cells from participants’ blood will be cultured and kept alive forever to further 
study their DNA). The purpose of establishing a cell line is to create a source of DNA for storage in a 
repository for future research. The research on DNA and drug abuse will continue for a long time, and so 
your DNA may be available to researchers indefinitely. However, you may indicate at the end of this form 
how your genetic sample is used (check one). For the current study, samples will only be kept for a 
maximum of 5 years. If you change your mind about having your DNA used in future related research, 
you can tell us to remove and destroy the samples any time during or after the study. However, if you 
consent to having your sample used to create cell lines, you will not be able to withdraw consent to its 
use, since identifying information will be removed. 
 
Study Risks 
 
Amphetamine Administration: Amphetamine drugs are considered to have a high potential for abuse and 
there have been reports of death and potentially a heart attack associated with their use. In addition, on 
rare occasions amphetamine use has been associated with chest pain, temporary hallucinations (seeing 
and hearing things that were not present), disorientation, seizures and muscle stiffness. You may also 
experience: excitation, restlessness, anxiety, headache, dry mouth, diarrhea, constipation, rapid pulse, 
loss of appetite, fluttering of the heart, irregular heart beats, and occasionally nausea, dizziness, 
sedation, or tremors. 
 
The risks of snorting methamphetamine have not been well characterized. In addition to likely 
nasal tissue irritation and bleeding, we cannot rule out the possibility of more significant adverse 
effects including loss of smell, lung damage, inflammation and infection.   
 
Naltrexone Administration: Naltrexone may mildly impair the functioning of the liver. This effect on the 
liver will improve after naltrexone is discontinued. Naltrexone may also cause stomach upset, nausea, 
and vomiting. In addition, administration of naltrexone may increase blood sugar levels, which may 
produce symptoms such as dizziness, increased breathing, dehydration, sedation, and seizures. If you 
regularly use opioid medications like oxycodone or heroin, naltrexone may cause you to experience 
withdrawal symptoms.  
 
Behavioral Tasks Risks: You may feel uncomfortable discussing sexual behaviors.  
 
Pregnancy Risks: If you are female in your childbearing years, you will be asked to take a pregnancy test 
to ensure that you are not pregnant. If you are pregnant or trying to become pregnant, there may be risks 
to you or your unborn child. If you are nursing an infant, there may be risks to the infant.  Females must 
be either post-menopausal, surgically sterilized, or use an acceptable method of contraception (double 
barrier method like a condom with a spermicidal lubricant) to participate in this study. 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
4
 
Risks to Privacy: As in any research study, it is possible that personal information about you could 
become known to other people. The investigators will take precautions to prevent this from happening. 
Your name will not appear on any questionnaires or test that you complete during the study. Instead, all 
questionnaires and tests you complete will be coded with a study code number.  
 
Unknown/Unforeseeable Risks: In addition to the risks listed above, there may be some unknown or 
infrequent and unforeseeable risks associated with the use of this study drug. If you experience any 
symptoms you believe to be related to the study drug you should call the study staff at 646-774-6243. 
 
 
Study Benefits: You are not expected to benefit directly from participation in this study.  
 
 
New Information:  You will be informed verbally and in writing of any new information, findings or 
changes to the way the research will be performed that might change your willingness to continue your 
participation in this study. 
 
 
Compensation: You will receive $125 for each of the four completed laboratory sessions and $50 for the 
follow-up visit. With the additional money you could earn during the laboratory sessions, you could make 
up to $610.  Failure to comply with the study could result in dismissal from the study. If you are dismissed 
from the study or decide to withdraw from the study, you will still receive the payment for the parts that 
you completed.   
 
We are required by law to report your earnings to the IRS.  Therefore, your Social Security Number and 
amount earned will be reported, and you will receive the appropriate IRS form at the end of the year in 
which you were paid.  Please note that payment for this study may affect your eligibility for Medicaid and 
other city and state support services.  No information about which study you participated in will be 
provided to the IRS.   
 
Confidentiality: All written information acquired in this study will be stored in locked files and will be kept 
confidential to the extent permitted by law. All computer-stored information will be "coded"—labeled only 
with a code and on password-protected computers. These code numbers will not use a name or any 
other identifying features. Your name and other personal identifying information will be stored in an 
electronically secure database at New York Psychiatric Institute that is accessible only to the members of 
the research team.  
 
We have applied for a Certificate of Confidentiality issued by the National Institute on Drug Abuse. With 
this certificate, the researchers cannot be forced to release any research information in which you are 
identified, even under a court order or subpoena, without your written consent. The Certificate does not 
prevent the researchers from reporting suspected or known neglect or sexual or physical abuse of a 
child, or threatened violence to self or others. Such information will be reported to the appropriate 
authorities. You should understand that a Certificate of Confidentiality does not prevent you or a member 
of your family from voluntarily releasing information about yourself or your involvement in this research. If 
an insurer, employer, or other person obtains your written consent to receive research information, then 
the researchers may not use the Certificate to withhold that information. Records will be available to 
research staff, and Federal, State, and Institutional regulatory personnel (who may review records as 
part of the routine audits). 
Your genetic information will be kept confidential and de-identified. All records containing links and 
identifying information will be kept in locked files and on password-protected computers. This information 
will only be available to NYSPI personnel key to this investigation.  Your blood sample will be labeled 
with a code that will be used throughout screening and testing. The sample will not have your name, or 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
5
address on it. The laboratories carrying out the DNA analysis (Columbia University, Human Genetics 
Resources Core, 630 W. 168th St. New York, NY 10032) and LGC Genomics (100 Cumming Center, 
Beverly, MA 01915) will never know your identity. If you also agree to have your DNA stored for future 
research, this number will be removed from your sample so there will be no way to know that it came 
from you, and it will not be possible to trace your identity.  
 
The Genetic Information Nondiscrimination Act (GINA) provides additional protections for you against 
discrimination based upon your private genetic information. This Federal law generally makes it illegal for 
health insurance companies, group health plans, and most employers to discriminate against you based 
on your genetic information.  GINA does not protect you against genetic discrimination by companies that 
sell life insurance, disability insurance, or long-term care insurance or by adoption agencies. GINA also 
does not protect you against discrimination based on an already diagnosed genetic condition or disease. 
If you would like to know more about it you can discuss this with the principal investigator of this study 
(Dr. Jones, 646 774-6113) or you can go to the following website http://www.genome.gov/10002328. 
 
 
In Case of Injury 
 
In case of injury, New York State Psychiatric Institute will provide short term emergency medical 
treatment, which has been determined to be necessary by New York State Psychiatric Institute's doctors, 
and which is within the capability of New York State Psychiatric Institute to provide.  In addition, we will 
provide assistance in arranging follow up care in such instances. 
 
New York State Psychiatric Institute and Research Foundation for Mental Hygiene do not provide 
compensation or payment for treatment of research related injuries.  However, you should be aware that 
you do not give up your legal right to seek such compensation through the court by participating in this 
research. 
 
Questions 
The investigators will answer to the best of his/her ability any questions that the participant may have 
now or in the future about the research procedures, or about the subject's response to the procedures.  
You may contact the Principal Investigator, Dr. Jermaine Jones who can be reached at (646) 774-6113, if 
you have any questions. You will be given a copy of this consent form to take home with you. You will be 
notified of any significant new findings that may relate to your willingness to continue to participate in this 
study.   
 
 If you have any questions about your rights as a research participant, want to provide feedback, or have 
a complaint, you may call the NYSPI Institutional Review Board (IRB). An IRB is a committee that 
protects the rights of human subjects in research studies. You may call the IRB Main Office at (646) 774-
7155 during regular office hours. 
 
 
Documentation of Consent 
 
Dr. Jones may □, may not □ use my genetic sample can be used for the current study. 
Dr. Jones may □, may not □ use my genetic sample for future related studies of drug abuse. 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
6
Dr. Jones may □, may not □ use my genetic sample to create cell lines from my DNA for 
storage at a national repository.   Once the trial ends, I will not be able to request the destruction 
of the sample because the link of my DNA sample to my identity will have been removed. 
 
 
 
I have read and understand the preceding information describing this medical research study.  The study 
doctor or the study staff has explained it to me in detail and all of my questions have been answered to 
my satisfaction.   
 
I understand that I will receive a signed copy of this consent form for my records.  I voluntarily agree to 
participate in the research study described above. 
 
 
Name of Participant__________________________________  
 
 
Signature of Participant_______________________________ Date_______________  
 
 
Statement of the Investigator (M.D.)  
 
I have examined the participant named above for the purpose of determining whether he/she is capable 
of understanding the purpose, nature, risks, benefits and alternatives (including non-participation) of the 
research, making decisions about participation, and understanding that the decision about participation 
in the research will involve no penalty or loss of benefits to which the patient is otherwise entitled, for Dr. 
Jermaine Jones’ research project “Using Pharmacogenetics to Better Evaluate Naltrexone for Treating 
Stimulant Abuse.” On the basis of this examination I have arrived at the conclusion that this participant 
has this capacity at this time. 
 
 
Printed Name__________________________________  
 
 
Signature______________________________________Date________________  


 
PI: JONES, JERMAINE D
Title: Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant
Abuse
Received: 07/15/2015
FOA: PA14-013
Council: 01/2016
Competition ID: FORMS-C
FOA Title: Functional Genetics, Epigenetics, and Non-coding RNAs in Substance
Abuse (R21)
1 R21 DA040225-01A1
Dual: 
Accession Number: 3845406
IPF: 1590919
Organization: NEW YORK STATE PSYCHIATRIC INSTITUTE
Former Number: 
Department: 110 NYPI Substance Abuse
IRG/SRG: GHD
AIDS: N
Expedited: N
Subtotal Direct Costs
(excludes consortium F&A) 
Year 1:      150,000 
Year 2:      125,000
Animals: N 
Humans: Y 
Clinical Trial: N 
Current HS Code: 30 
HESC: N
New Investigator: N 
Early Stage Investigator: N
 
Senior/Key Personnel: 
Organization: 
Role Category: 
Jermaine Jones  
Research Foundation for Mental
Hygiene, Inc.
PD/PI
Sandra Comer PhD
Research Foundation for Mental
Hygiene, Inc.
Co-Investigator
Shanthi Mogali  
Research Foundation for Mental
Hygiene, Inc.
Co-Investigator
Henry Kranzler MD
University of Pennsylvania
Consultant
 
Appendices 
BDI,CGI,DAST,TSR,MEDICAL HISTORY QUESTIONNAIRE,Intake Questionnaire,Substance Use Inventory,RAB,Self-Report
ASI_1,SCI


OMB Number: 4040-0001
Expiration Date: 06/30/2016
Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013 . Received Date:
2015-07-15T14:35:23.000-04:00
APPLICATION FOR FEDERAL ASSISTANCE
SF 424 (R&R)
3. DATE RECEIVED BY STATE
State Application Identifier
1. TYPE OF SUBMISSION*
4.a. Federal Identifier
DA040225
❍ Pre-application
● Application
❍ Changed/Corrected
Application
b. Agency Routing Number
 
2. DATE SUBMITTED
2015-07-15
Application Identifier
PD/2015/01123
c. Previous Grants.gov Tracking Number
5. APPLICANT INFORMATION
Organizational DUNS*: 1672049940000
Legal Name*:
Research Foundation for Mental Hygiene, Inc.
Department:
110 NYPI Substance Abuse
Division:
Street1*:
NYPI
Street2:
1051 Riverside Dr
City*:
New York
County:
New York
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES
ZIP / Postal Code*:
10032-1007
Person to be contacted on matters involving this application
Prefix:  Ms.
First Name*:  Janelle
Middle Name:  Rene
Last Name*:  Greenhill
Suffix:  MPH
Position/Title:
Director of Administration
Street1*:
NYPI
Street2:
1051 Riverside Dr
City*:
New York
County:
New York
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES
ZIP / Postal Code*:
10032-1007
Phone Number*: 646-774-6500
Fax Number: 646-774-6540
Email: nga@rf.cpmc.columbia.edu
6.  EMPLOYER IDENTIFICATION NUMBER (EIN) or (TIN)*
1141410842A2
7.  TYPE OF APPLICANT*
M: Nonprofit with 501C3 IRS Status (Other than Institution of Higher
Education)
Other (Specify):
Small Business Organization Type
❍ Women Owned
❍ Socially and Economically Disadvantaged
8.  TYPE OF APPLICATION*
If Revision, mark appropriate box(es).
❍ New
● Resubmission
  ❍ A. Increase Award
❍ B. Decrease Award
❍ C. Increase Duration
❍ Renewal
❍ Continuation
❍ Revision
  ❍ D. Decrease Duration ❍ E. Other (specify) :
Is this application being submitted to other agencies?*
❍Yes
●No
What other Agencies?
9.  NAME OF FEDERAL AGENCY*
National Institutes of Health
10. CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER
93.279
TITLE: Drug Abuse and Addiction Research Programs
11. DESCRIPTIVE TITLE OF APPLICANT'S PROJECT*
Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse
12. PROPOSED PROJECT
Start Date*
Ending Date*
04/01/2016
03/31/2018
13. CONGRESSIONAL DISTRICTS OF APPLICANT
NY-013


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013 . Received Date:
2015-07-15T14:35:23.000-04:00
SF 424 (R&R) APPLICATION FOR FEDERAL ASSISTANCE
Page 2
14. PROJECT DIRECTOR/PRINCIPAL INVESTIGATOR CONTACT INFORMATION
Prefix:  Dr.
First Name*:  Jermaine
Middle Name:  D
Last Name*:  Jones
Suffix: 
Position/Title:
Research Scientist IV
Organization Name*:
Research Foundation for Mental Hygiene, Inc.
Department:
110 NYPI Substance Abuse
Division:
Street1*:
NYPI
Street2:
1051 Riverside Dr
City*:
New York
County:
New York
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES
ZIP / Postal Code*:
10032-1007
Phone Number*: 646-774-6113
Fax Number: 646-774-6111
Email*: jonesje@nyspi.columbia.edu
15. ESTIMATED PROJECT FUNDING
a. Total Federal Funds Requested*
$445,500.00
b. Total Non-Federal Funds*
$0.00
c. Total Federal & Non-Federal Funds*
$445,500.00
d. Estimated Program Income*
$0.00
16. IS APPLICATION SUBJECT TO REVIEW BY STATE
EXECUTIVE ORDER 12372 PROCESS?*
a. YES
❍THIS PREAPPLICATION/APPLICATION WAS MADE
AVAILABLE TO THE STATE EXECUTIVE ORDER 12372
PROCESS FOR REVIEW ON:
DATE:
b. NO
●PROGRAM IS NOT COVERED BY E.O. 12372; OR
❍PROGRAM HAS NOT BEEN SELECTED BY STATE FOR
REVIEW
17.  By signing this application, I certify (1) to the statements contained in the list of certifications* and (2) that the statements herein
are true, complete and accurate to the best of my knowledge. I also provide the required assurances * and agree to comply with
any resulting terms if I accept an award. I am aware that any false, fictitious, or fraudulent statements or claims may subject me to
criminal, civil, or administrative penalties. (U.S. Code, Title 18, Section 1001)
● I agree*
* The list of certifications and assurances, or an Internet site where you may obtain this list, is contained in the announcement or agency specific instructions.
18. SFLLL or OTHER EXPLANATORY DOCUMENTATION
File Name: 
19. AUTHORIZED REPRESENTATIVE
Prefix:  Ms.
First Name*:  Janelle
Middle Name:  Rene
Last Name*:  Greenhill
Suffix:  MPH
Position/Title*:
Director of Administration
Organization Name*:
Research Foundation for Mental Hygiene, Inc.
Department:
110 NYPI Facilities and Admini
Division:
Street1*:
NYPI
Street2:
1051 Riverside Dr
City*:
New York
County:
New York
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES
ZIP / Postal Code*:
10032-1007
Phone Number*: 646-774-6500
Fax Number: 646-774-6540
Email*: nga@rf.cpmc.columbia.edu
Signature of Authorized Representative*
Ms. Janelle Rene Greenhill MPH
Date Signed*
07/15/2015
20. PRE-APPLICATION     File Name:    Mime Type:
21. COVER LETTER ATTACHMENT   File Name:   Mime Type:
Contact PD/PI: Jones, Jermaine D


424 R&R and PHS-398 Specific
Table Of Contents
Page Numbers
SF 424 R&R Cover Page-----------------------------------------------------------------------------------------
1
                    Table of Contents-------------------------------------------------------------------------
3
Performance Sites---------------------------------------------------------------------------------------------
4
Research & Related Other Project Information------------------------------------------------------------------
5
                    Project Summary/Abstract(Description)-----------------------------------------------------
6
                    Project Narrative-------------------------------------------------------------------------
7
                    Facilities & Other Resources--------------------------------------------------------------
8
Research & Related Senior/Key Person--------------------------------------------------------------------------
9
PHS398 Cover Page Supplement----------------------------------------------------------------------------------
30
PHS 398 Modular Budget----------------------------------------------------------------------------------------
32
                    Personnel Justification-------------------------------------------------------------------
35
                    Additional Narrative Justification--------------------------------------------------------
38
PHS 398 Research Plan-----------------------------------------------------------------------------------------
39
                    Introduction------------------------------------------------------------------------------
40
                    Specific Aims-----------------------------------------------------------------------------
41
                    Research Strategy-------------------------------------------------------------------------
42
                    Human Subjects Section--------------------------------------------------------------------
48
                                        Protection of Human Subjects------------------------------------------
48
                                        Women & Minorities----------------------------------------------------
53
                                        Planned Enrollment Report---------------------------------------------
54
                                        Children--------------------------------------------------------------
55
                    Bibliography & References Cited-----------------------------------------------------------
56
                    Letters Of Support------------------------------------------------------------------------
63
                    Resource Sharing Plans--------------------------------------------------------------------
64
Appendix
Number of Attachments in Appendix: 10
Table of Contents                                                                                             Page 3
Contact PD/PI: Jones, Jermaine D


OMB Number: 4040-0010
Expiration Date: 06/30/2016
Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date:
2015-07-15T14:35:23.000-04:00
Project/Performance Site Location(s)
 
Project/Performance Site Primary Location
❍ I am submitting an application as an individual, and not on behalf of
a company, state, local or tribal government, academia, or other type of
organization.
Organization Name:
Research Foundation for Mental Hygiene, Inc.
Duns Number:
1672049940000
Street1*:
Research Foundation for Mental Hygiene, Inc
Street2:
1051 Riverside Drive
City*:
New York
County:
NY
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES 
Zip / Postal Code*:
10032-1007
Project/Performance Site Congressional District*:
NY-013
File Name
Mime Type
Additional Location(s)
                                                                                                              Page 4
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date:
2015-07-15T14:35:23.000-04:00
OMB Number: 4040-0001
Expiration Date: 06/30/2016
RESEARCH & RELATED Other Project Information
 
1. Are Human Subjects Involved?*
●Yes
❍No
1.a. If YES to Human Subjects
 
Is the Project Exempt from Federal regulations?
❍Yes
●No
 
If YES, check appropriate exemption number:
1
2
3
4
5
6
 
If NO, is the IRB review Pending?
●Yes
❍No
 
IRB Approval Date:
 
Human Subject Assurance Number
00006105
2. Are Vertebrate Animals Used?*
❍Yes
●No
2.a. If YES to Vertebrate Animals
Is the IACUC review Pending?
❍Yes ❍No
IACUC Approval Date:
Animal Welfare Assurance Number
3. Is proprietary/privileged information included in the application?*
❍Yes
●No
4.a. Does this project have an actual or potential impact - positive or negative - on the environment?*
❍Yes
●No
4.b. If yes, please explain:
4.c. If this project has an actual or potential impact on the environment, has an exemption been authorized or an
environmental assessment (EA) or environmental impact statement (EIS) been performed?
❍Yes
❍No
4.d. If yes, please explain:
5. Is the research performance site designated, or eligible to be designated, as a historic place?*
❍Yes
●No
5.a. If yes, please explain:
6. Does this project involve activities outside the United States or partnership with international
collaborators?*
❍Yes
●No
6.a. If yes, identify countries:
6.b. Optional Explanation:
Filename
7. Project Summary/Abstract*
Project Summary 7-15-15_1.pdf
Mime Type: application/octet-
stream
8. Project Narrative*
Project Narrative 7-15-15_1.pdf
Mime Type: application/octet-
stream
9. Bibliography & References Cited References 7-13-15.pdf
Mime Type: application/octet-
stream
10.Facilities & Other Resources
Facilities_Resources_Jones.pdf
Mime Type: application/octet-
stream
11.Equipment
                                                                                                              Page 5
Contact PD/PI: Jones, Jermaine D


PROJECT SUMMARY 
There is thought to be over 75 milliion abusers of amphetamines (AMPHs) and cocaine worldwide.  Unlike 
drugs such as heroin, alcohol or nicotine, there is no FDA-approved medication to facilitate the treatment of 
psychostimulant abuse. Several preclinical and clinical studies have provided data suggesting that naltrexone 
(NTX) may have potential for this indication. However, a review of the literature reveals conflicting findings that 
require resolution. Several clinical studies have shown that genetic variation moderates the effects of a number 
of medications used to treat substance use disorders. A recent meta-analysis concluded that the OPRM1 
A118G SNP (rs1799971) significantly moderates the treatment efficacy of NTX in treating alcohol abuse, 
increasing the treatment efficacy by over 2 fold among G-allele carriers (AG/GG).  The proposed application 
would be the first to investigate the moderating effect of this genotype in the efficacy of NTX to treat stimulant 
abuse. More specifically, we propose investigating the interaction between NTX and intranasal (IN) 
methamphetamine (50mg/70kg). Participants who meet DSM-V criteria for moderate-to-severe stimulant use 
disorder will complete testing sessions where the abuse liability of IN methamphetamine (M-AMPH) is 
assessed following pretreatment with NTX (0, 25, 50 mg). Naltrexone’s effects upon the abuse potential of IN 
M-AMPH will be assessed using self-report measurements of positive subjective effects and drug self-
administration. Medication effects on these validated predictors of abuse will be compared between A118G A 
allele homozygotes (AA) and G-allele carriers (AG/GG; an anticipated 25% of the total sample), in order to 
assess genetic moderation of treatment outcome. The advantage of this approach is that it may help to define 
individuals in which the treatment exerts its greatest effects. As a secondary aim of the study we will 
simultaneously assess for possible moderating effects of several functionally relevant genetic variants to 
predict the how NTX alters the subjective and reinforcing effects of IN M-AMPH [ANKK1 (rs1800497); DβH 
(rs1611115); DRD2 (rs2283265); OPRM1 (rs6912029); SLC6A3 (rs28363170)]. This study therefore utilizes a 
focused approach to assess the influence of a genetic polymorphism whose influence has been substantiated 
by other investigations, and an exploratory approach to assess the individual and combined influence of 
several likely genetic moderators.  Combined, the two studies in this proposal will contribute to the assessment 
of the clinical utility of NTX for treating psychostimulant abuse, and may help identify gene x pharmacological 
interactions contributing to the personalization of treatment. 
 
Project Summary/Abstract                                                                                      Page 6
Contact PD/PI: Jones, Jermaine D


Project Narrative 
The proposed investigation will be the first study assessing genetic modulation of naltrexone’s 
effects upon the abuse liability of a stimulant drug (methamphetamine). An exploratory study will 
concurrently assess the ability of several functionally relevant gene variants to predict 
pharmacological treatment efficacy.  In addition to its contribution to the further development of 
the first pharmacotherapy for stimulant abuse, this study may identify gene x pharmacological 
interactions contributing to the personalization of stimulant abuse pharmacotherapy. 
Project Narrative                                                                                             Page 7
Contact PD/PI: Jones, Jermaine D


Clinical Resources
New York State Psychiatric Institute (NYSPI) and the Columbia University Medical Center (CUMC) Department of 
Psychiatry together form an active academic medical center and leading teaching hospital that have attracted a 
distinguished group of research scientists who provide leadership across the breadth of modern psychiatry. The 
Department of Psychiatry is one of the largest in the country in terms of faculty size as well as state, federal, and 
foundation research support, and includes over 400 clinical and basic science faculty. The New York State 
Psychiatric Institute is located in New York City, where it is easily accessible by public transportation and fully 
equipped to conduct clinical research.  The facilities at the NYSPI include 36 clinical research beds, 4 residential 
research beds, 22 clinical beds, 5 research clinics, animal quarters, a computer center, a research library, and 
over 100,000 square feet of laboratory space.  The clinic space is configured with individual psychotherapy 
offices, classrooms, subject testing rooms, and medical examination facilities.  The NYSPI Pharmacy has a Class 
IV Institutional License that allows for the distribution of controlled substances for research conducted within the 
Division. The NYSPI is the primary site for the Division on Substance Abuse and the proposed application, as well 
as numerous R01’s to various Division faculty. The Division on Substance Abuse consists of over thirty 
individuals who are involved in the Division’s numerous research protocols and clinical services. The clinical staff 
is comprised of psychiatrists, consulting internists and cardiologists, doctoral-level psychologists, master-level 
therapists, and nurses. Research in the Division focuses on antecedents and consequences of substance use 
and abuse, with particular emphasis on the development and testing of novel approaches to the treatment of 
substance abuse. 
Laboratory Resources
The Central Reference Laboratory of the Nathan Kline Institute (NKI) for Psychiatric Research will perform blood 
and urine testing for the proposed project. The Central Reference Laboratory serves as the primary clinical 
laboratory for all clinical facilities of the New York State Office of Mental Health. Specimens are sent by express 
mail or private courier. The laboratory is equipped with standard instruments: centrifuges, spectrophotometer, 
shaker, high-pressure liquid chromatograph, scintillation spectrometer, as well as other specialized equipment. 
The Human Genetics Resources Core of Columbia University will provide DNA isolation and storage services for 
the current proposal.  Under the direction of Dr. Richard Mayeux the HGRC is designed to facilitate genetic 
research in human populations campus-wide. It has three components: 1) Cell and DNA Repository for tissue 
culture, cell banking and DNA isolation and storage); 2) Database Management Systems for tracking of laboratory 
and clinical research information. This Core is a resource for all departments, centers and institutes that wish to 
perform genetic research in human populations. As such, it represents a key component of human genetics 
research at Columbia University Medical Center.
The Taub Institute Genomics Core of Columbia University will act as our SNP genotyping service laboratory.  
Directed by Dr. Lorraine Clark, Taub provides all investigators at CUMC and NYSPI  with PCR-based 
Genotyping, CNV Analysis, Gene Expression Analysis and Methylation Analysis; along with data analysis support  
for the coordination of statistical analysis of genetic data from human studies. The DNA facility has the latest 
sequencing technology including:  Affymetrix GeneChip System, Illumina Iscan, Sequenom Mass Array Compact 
System, and NanoDrop-1000 Spectrophotometer.  The facility can process Affymetrix Gene Chips using both 
expression and DNA genotyping products.  Further expression data can also be obtained using the facility's real-
time PCR instrument. Investigators are also able to consult with the facility director to determine the best method 
for their study, based on project goals, sample number and SNP density.
Computer
Computer users at NYSPI are provided with network maintenance consultation and connection to the internet and 
email. This includes access to PubMed, Medline, and the wide array of medical psychiatric, and substance abuse 
journals available in electronic form. Access also will be available to NYSPI computer facilities, which contain a 
variety of statistical and graphics (illustration, statistics-related) software. 
Office
Office space is provided through Columbia University and NYSPI. 
Major Equipment
No other major equipment will be needed.
Facilities & Other Resources                                                                                  Page 8
Contact PD/PI: Jones, Jermaine D


OMB Number: 4040-0001
Expiration Date: 06/30/2016
Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013 . Received Date:
2015-07-15T14:35:23.000-04:00
RESEARCH & RELATED Senior/Key Person Profile (Expanded)
 
PROFILE - Project Director/Principal Investigator
Prefix: Dr.
First Name*: Jermaine
Middle Name D
Last Name*: Jones
Suffix: 
Position/Title*:
Research Scientist IV
Organization Name*:
Research Foundation for Mental Hygiene, Inc.
Department:
110 NYPI Substance Abuse
Division:
Street1*:
NYPI
Street2:
1051 Riverside Dr
City*:
New York
County:
New York
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES
Zip / Postal Code*:
10032-1007
Phone
Number*: 646-774-6113
Fax Number: 646-774-6111
E-Mail*: jonesje@nyspi.columbia.edu
Credential, e.g., agency login: JONESJER
Project Role*:  PD/PI
Other Project Role Category: 
Degree Type:  PHD
Degree Year:  2004
 
File Name
Mime Type
Attach Biographical Sketch*:
Jones Biosketch 7-15-15.pdf
application/octet-stream
Attach Current & Pending Support:
 
                                                                                                              Page 9
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013 . Received Date:
2015-07-15T14:35:23.000-04:00
PROFILE - Senior/Key Person
Prefix: Dr.
First Name*: Sandra
Middle Name D
Last Name*: Comer
Suffix: PhD
Position/Title*:
Research Scientist Level V-NL
Organization Name*:
Research Foundation for Mental Hygiene, Inc.
Department:
110 NYPI Substance Abuse
Division:
Street1*:
NYPI
Street2:
1051 Riverside Dr
City*:
New York
County:
New York
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES
Zip / Postal Code*:
10032-1007
Phone Number*: (646)
774-6146
Fax Number: 212-543-5991
E-Mail*: comersa@nyspi.columbia.edu
Credential, e.g., agency login: scomer
Project Role*:  Co-Investigator
Other Project Role Category: 
Degree Type: 
Degree Year:  1992
 
File Name
Mime Type
Attach Biographical Sketch*:
Comer_Bio_7-13-15.pdf
application/octet-stream
Attach Current & Pending Support:
 
PROFILE - Senior/Key Person
Prefix: 
First Name*: Shanthi
Middle Name 
Last Name*: Mogali
Suffix: 
Position/Title*:
Technical Specialist Level III
Organization Name*:
Research Foundation for Mental Hygiene, Inc.
Department:
110 NYPI Substance Abuse
Division:
Street1*:
NYPI
Street2:
1051 Riverside Dr
City*:
New York
County:
New York
State*:
NY: New York
Province:
Country*:
USA: UNITED STATES
Zip / Postal Code*:
10032-1007
Phone
Number*: 646-774-6147
Fax Number: 
E-Mail*: mogalis@nyspi.columbia.edu
Credential, e.g., agency login: SMogali
Project Role*:  Co-Investigator
Other Project Role Category: 
Degree Type: 
Degree Year: 
 
File Name
Mime Type
Attach Biographical Sketch*:
Mogali_Bio_Jones_R01_7_6_15.pdf
application/octet-stream
Attach Current & Pending Support:
 
                                                                                                              Page 10
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013 . Received Date:
2015-07-15T14:35:23.000-04:00
PROFILE - Senior/Key Person
Prefix: 
First Name*: Henry
Middle Name R
Last Name*: Kranzler
Suffix: MD
Position/Title*:
Professor of Psychiatry
Organization Name*:
University of Pennsylvania
Department:
Psychiatry
Division:
Street1*:
Treatment Research Center
Street2:
Perelman School of Medicine
City*:
Philadelphia
County:
State*:
PA: Pennsylvania
Province:
Country*:
USA: UNITED STATES
Zip / Postal Code*:
19104-6178
Phone
Number*: 215-222-3200
Fax Number: 215-386-6770
E-Mail*: kranzler@mail.med.upenn.edu
Credential, e.g., agency login: henrykranzler
Project Role*:  Consultant
Other Project Role Category: 
Degree Type:  MD
Degree Year:  1982
 
File Name
Mime Type
Attach Biographical Sketch*:
Kranzler Jermaine Jones R21
7-10-15.pdf
application/octet-stream
Attach Current & Pending Support:
 
                                                                                                              Page 11
Contact PD/PI: Jones, Jermaine D


  
 
 
BIOGRAPHICAL SKETCH 
Provide the following information for the Senior/key personnel and other significant contributors. 
Follow this format for each person.  DO NOT EXCEED FIVE PAGES. 
NAME 
Jones, Jermaine Dionte 
POSITION TITLE 
Research Scientist IV & Assistant Professor of 
Clinical Neurobiology 
eRA COMMONS USER NAME (credential, e.g., agency login) 
Jonesjer 
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) 
INSTITUTION AND LOCATION 
DEGREE 
(if applicable) 
YEAR(s) 
FIELD OF STUDY 
University of Virginia: Charlottesville, VA 
B.A. 
98’-02’ 
Biology/Psychology 
Old Dominion University: Norfolk, VA 
M.S. 
02’-04’ 
Psychology 
American University: Washington, D.C 
Ph.D. 
04’-08’       Behavioral Neurobiology 
Columbia University/NYSPI: New York, NY 
Fellowship 
08’-11’ 
Drug Abuse 
 
 
 
 
A. Personal Statement. 
 
The goal of the proposed study is to examine the influence of OPRM1 gene variant (A118G, rs1799971) on the 
ability of naltrexone to alter the abuse liability of methamphetamine. An exploratory aim of the project will also 
assess the association between various relevant function gene variants on treatment response. I joined the 
Substance Abuse Division in 2008 as a post-doctoral fellow working in the Opioid Research Laboratory under 
Dr. Sandra Comer (Director). In 2011 I became a junior faculty member working on my K01 study investigating 
genetic contribution to the abuse potential of opioids. As a part of my K01 career development plan, I have 
attempted to develop a research niche within our Division investigating the pharmacogenetics of drugs abuse 
as it relates to changes in subjective effects (e.g. stronger positive subjective effects, weakened aversive 
effects) and treatment outcome. Since beginning my foray into this area of research 4 years ago, I have also 
completed coursework at Columbia’s Mailman School of Public Health (P6385: Molecular Genetics and the 
Environment), The Jackson Laboratory (Genetics of Addiction) and the National Institute of General Medical 
Science (NIGMS) (Statistical Genetics).  Since joining Columbia’s Substance Abuse Division, I have gained 
significant expertise executing clinical investigations and combined with my recent endeavors in genetic 
research, I believe these experiences qualify me to oversee the completion of this project. 
Most relevant to the current application  
 
 
Jones J.D., & Comer S.D. (2015) A Review of Pharmacogenetic Studies of Drug Use Disorders. Drug 
and Alcohol Dependence, 152:1-14. PMCID: PMC4458176. 
 
 
Jones J.D., Comer S.D., & Kranzler H.R. (2015) The Pharmacogenetics of Alcohol: A Critical Review. 
Alcoholism: Clinical and Experimental and Research, 39: 391-402. PMCID: PMC4348335 
 
Jones J.D., Luba R.L., Vogelman J., & Comer S.D. Evidence of Genetic Modulation of Opioid 
Withdrawal Severity. Pharmacology, Biochemistry and Behavior (Submitted). 
 
B. Positions and Honors. 
 
Positions and Employment 
2003-2004  
Health Education Coordinator, Old Dominion University 
2007-2008  
 
Adjunct Lecturer, University of the District of Columbia 
2008-2011  
      Post-Doctoral Fellow, Columbia University/NYSPI 
2011-Present        Adjunct Lecturer, City College of New York 
Biosketches                                                                                                   Page 12
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2011-Present  
Adjunct Lecturer, St. John’s University  
2011-Present        Assistant Professor of Clinical Neurobiology, Columbia University/NYSPI 
 
Professional Memberships 
2002-2004  
 
Virginia Academy of Science 
2004-2007  
      Society for Neurosciences (SfN) 
2006-2008   
 
International Behavioral Neuroscience Society (IBNS) 
2007-Present  
American Psychological Association 
2009-Present  
College on Problems of Drug Dependence (CPDD): Associate Member 
2012-Present   
International Study Group Investigating Drugs as Reinforcers 
 
 
Honors 
2004   
 
 
Johns Hopkins University: Ivor and Colette Royston Research Program Award 
2005   
 
 
American Psychological Association: Diversity in Neuroscience Pre-doctoral Fellowship 
2005   
 
 
Marine Biological Laboratory: Summer Program in Neuroscience Fellowship 
2006  
 
 
The College of Problems on Drug Dependence: Primm-Singleton Travel Fellowship 
2007   
 
 
International Behavioral Neuroscience Society: Travel Award Recipient 
2009  
 
 
Jackson Laboratory Short Course on Mammalian Genetics: Scholarship Recipient  
2010   
 
      NIDA Genetic Approaches to Understand Drug Abuse and Addiction Meeting: Travel Award 
2010                      International Narcotics Research Conference: Young Investigator Travel Award 
2012  
 
      CPDD Minority Early Stage Investigator Conference Stipend: Award Recipient 
2012  
 
 
American College of Neuropsychopharmacology: Travel Award 
2013  
 
 
College on Problems of Drug Dependence: Early Career Investigator Award 
2014  
 
 
Association for Medical Education and Research in Substance Abuse: Travel Award 
2014  
 
 
Society for Neuroscience, Frontiers in Addiction Research: Travel Award 
2015  
 
 
American Psychological Association (APA): International Conference Travel Grant 
2015  
 
 
Society of Addiction Psychology/NIDA: Early-Career Investigator Award 
 
C. Contribution to Science 
1. Critical, constructive analyses of the drug abuse literature through summary, classification, analysis and 
comparison.  
 
As a young investigator, I feel my greatest contributions to the field has come from my efforts to gather, 
summarize and critique relevant studies in order to discuss the state of a significant research question. As 
with any area of research, rarely does a single study answer a research question sufficiently to lead to 
scientific consensus. All study methodologies (e.g., preclinical, clinical, laboratory, outpatient) have inherent 
limitations, along with the unique limitations of each individual investigation (e.g., sample size, 
generalizability, treatment duration etc., etc.). Therefore, reviews combining data across multiple studies 
provide a better framework for answering a research question, and are more likely to inform clinical care. To 
this affect, I have written a number of reviews in order to provide myself and other substance abuse 
researchers with a better understanding of several important topics.  
 
Jones J.D., & Comer S.D. (2015) The Epidemiology of Pain and Opioid Abuse. In Matthews, A.M., 
and Fellers, J. Treating Comorbid Opioid Use Disorder in Chronic Pain. New York, NY: Springer. 
 
 
Jones J.D., & Comer S.D. (2013) A review of human drug self-administration procedures.  Behavioural 
Pharmacology 24(5-6): 384-395. PMCID: PMC4080726 
 
 
Jones J.D., Mogali S. & Comer S.D. (2012) Polydrug abuse: A review of opioid and benzodiazepine 
combination use. Drug and Alcohol Dependence 125(1-2):8-18. PMCID: PMC3454351 
Biosketches                                                                                                   Page 13
Contact PD/PI: Jones, Jermaine D


 
 
 
 
Cooper Z.D., Jones J.D. & Comer S.D. (2012) Glial Inhibitors: A novel pharmacological approach to modulating 
the behavioral effects of abused substances. Expert Opin Investig Drugs 21(2); 169-178. PMCID: PMC3314383 
 
 
 
2.  Mediators and moderators of the abuse liability of opioids.  
 
Since completing my graduate training, most of my research has involved assessing the factors that 
mediate and moderate the reinforcing and subjective effects of opioids. In our controlled, clinical laboratory 
setting, my research has sought to better understand how factors such as: sex, genetic variation, route of 
administration, and state of dependence may lead to and/or maintain opioid abuse. Genetic moderation of 
the abuse liability of oxycodone is the focus of my K01 research study (DA030446). Additionally, my work 
has evaluated the ability of novel medications to alter laboratory measures of the reinforcing and positive 
subjective effects, as an indicator of their treatment potential. Overall, these studies have shown that the 
factors contributing to the abuse liability of opioids are multifaceted and nuanced, and it is difficult to 
produce attenuations in these effects that are clinically meaningful.   
 
Jones J.D., & Comer S.D. Novel Strategies for Reducing Opioid Abuse. Oral presentation at the 
International Narcotics Research Conference. Phoenix, AZ, June 2015. 
 
Jones, J.D., Sullivan, M.A., Manubay, J., Metz V., Mogali S., & Comer, S.D. (2015) The Effects of 
Pioglitazone, a PPARγ Receptor Agonist, on the Abuse Liability of Oxycodone. Addiction 
(Submitted). 
 
Jones J.D., Speer T., Nunes E., Comer S.D., Ross S., Rotrosen J. & Reid M.S. (2013) Opioid-like 
effects of the Neurokinin 1 antagonist aprepitant in patients maintained on and briefly withdrawn 
from methadone. American Journal of Drug and Alcohol Abuse 39(2): 86-91. PMCID: PMC3608205 
 
Jones J.D., Sullivan, M.A., Manubay, J.M., Vosburg, S.K., & Comer S.D. (2011) The subjective, 
reinforcing, and analgesic effects of oxycodone in patients with chronic, non-malignant pain who are 
maintained on sublingual buprenorphine/naloxone. Neuropsychopharmacology 36: 411–422. 
PMCID: PMC3055661 
3.  Ways to reduce the harms of opioid abuse. 
  
As outlined in the proposal, opioid abuse is a significant cause of mortality and morbidity.  My time as a 
fellow with the Division on Substance Abuse exposed me to the clinical aspects of drug use disorders. I 
feel my preclinical, genetic, and clinical background has given me a comprehensive view of the issues 
involved in drug abuse from susceptibility to treatment. As such, one of my areas of contribution has been 
to research ways to improve the lives of those suffering from opioid abuse. This area of study targets 
opioid abuse at its two most distal points, initiation and mortality. Among the relevant publications below is 
a study that provided the preliminary data for Dr. Comer’s R01 grant “Risk and Benefits of Overdose 
Education and Naloxone Prescribing to Heroin Users (DA035207).” With this project (on which I am a co-
investigator) we will attempt to study ways to improve overdose education and the availably of naloxone, in 
order to reduce opioid overdose fatality. The other work listed below suggests that we may circumvent the 
development of iatrogenic opioid abuse by preventing misuse of opioid analgesics, and highlights the 
unaddressed medical needs of those with active opioid use disorders.      
 
Jones J.D., Atchison J., Madera G., & Comer S.D. (2015) Need and utility of a polyethylene glycol 
marker to ensure against urine falsification among heroin users. Drug and Alcohol Dependence. doi: 
10.1016/j.drugalcdep.2015.05.021. PMCID: NIHMSID694927 
Biosketches                                                                                                   Page 14
Contact PD/PI: Jones, Jermaine D


 
 
 
Jones J.D., Roux P., Stancliff S., Matthews W., & Comer S.D. (2014) Brief overdose education can 
significantly increase accurate recognition of opioid overdose among heroin users. International 
Journal of Drug Policy 25:166-170. PMCID: PMC3864124 
 
Gudin J.A., Mogali S., Jones J.D., Comer S.D. (2013) Risks, management, and monitoring of 
combination opioid, benzodiazepines, and/or alcohol use. Postgraduate Medicine 125(4): 115-130. 
PMCID: PMC4057040 
 
 
Roux R., Jones J.D., & Comer S.D. (2013) Hepatitis C infection in non-treatment seeking heroin users:  
The burden of cocaine injection.  American Journal on Addictions 22(6): 613-618.  PMCID: 
PMC4059002 
 
For my complete bibliography see: 
http://www.ncbi.nlm.nih.gov/sites/myncbi/jermaine.jones.1/bibliography/41161959/public/?sort=dat
e&direction=descending. 
 
 
 D.  Research Support. 
 
Active 
 
K01 DA030446-04 (Jones) NIDA: 2011  
Mentored Research Scientist Development Award  
The research component of this grant investigates the contribution of genetic factors to the abuse potential of 
opioids. This grant also provides academic mentorship and support to help junior scientists become 
independent researchers. 
Role: Principal Investigator 
 
R01 DA035207-01 (Comer) NIDA: 2014  
This study examines the risk and benefits of current NYSDOH overdose education and naloxone prescribing to 
heroin users. 
Role: Co-investigator 
 
U54 DA037842-01 (Evans, Levin) NIDA: 2014 
Cooperative Agreement Specialized Center Grant 
Project 3 (PI: Comer) of the Division of Substance Abuse center grant involves testing of various novel 
compounds as possible therapeutics to treat opioid use disorders. 
Role: Junior Investigator 
 
 
Completed 
 
Reckitt-Benckiser (S.D. Comer):  2009 thru 2011 
Reinforcing Effects of Intranasal Buprenorphine versus Buprenorphine/Naloxone in Buprenorphine-Maintained 
Intranasal Drug Users. The purpose of this study in to compare the reinforcing effects of intranasally 
administered buprenorphine alone, and buprenorphine in combination with naloxone, in order to determine the 
abuse liability of Suboxone (buprenorphine/naloxone combination) through this route of administration. 
Role: Investigator 
 
T32 DA007294 (F.R. Levin)  NIDA: 2008 thru 2011     
Research Fellowship in Substance Abuse Disorders  
Biosketches                                                                                                   Page 15
Contact PD/PI: Jones, Jermaine D


 
 
This grant provides research and academic psychiatrists/psychologists with the skills and clinical experience 
necessary to advance our knowledge about the etiology and treatment of substance abuse disorders.  
Role: Fellow  
 
R01 DA022222 (S.D. Comer) NIDA: 2008 thru 2011  
Sustained-Release Naltrexone for Opioid Dependence: Longitudinal Study In Humans      
The purpose of this study is to examine the safety, effectiveness, and time course of a sustained-release  
implantable formulation of naltrexone for the treatment of heroin dependence.  
Role: Investigator  
  
R01 DA016759 (S.D. Comer) NIDA:  2008 thru 2011  
Prescription Opioid Effects in Drug and Non-drug Abusers  
This grant examines the reinforcing, subjective, performance, and physiological effects of prescription opioid  
medications (oxycodone, codeine) in drug and non-drug abusers under conditions of pain and no pain.  
Role: Investigator  
Biosketches                                                                                                   Page 16
Contact PD/PI: Jones, Jermaine D


 
 
 
BIOGRAPHICAL SKETCH 
Provide the following information for the Senior/key personnel and other significant contributors. 
Follow this format for each person.  DO NOT EXCEED FIVE PAGES. 
 
NAME 
Comer, Sandra D.  
 
POSITION TITLE 
Professor of Clinical Neurobiology 
Research Scientist VI 
eRA COMMONS USER NAME 
scomer 
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) 
INSTITUTION AND LOCATION 
DEGREE 
(if applicable) 
YEAR(s) 
FIELD OF STUDY 
Vanderbilt University, Nashville, TN 
B. S. 
1987 Psychology 
University of Michigan, Ann Arbor, MI 
M.S. 
1988 Biopsychology 
University of Michigan, Ann Arbor, MI 
Ph.D. 
1992 Biopsychology 
Univ. of Minnesota, Minneapolis, MN 
 
1993 Substance Abuse 
A. Personal Statement 
Stimulant abuse is a serious public health concern that is associated with increased morbidity and mortality. 
Although naltrexone has shown some promise for treating stimulant use disorder, clinical trials have yielded 
contrasting results. The studies proposed in the current application may address this problem by identifying 
populations of individuals who may who respond better or worse to naltrexone pharmacotherapy. For 20 years, 
my laboratory has investigated the pharmacological and behavioral factors affecting drug abuse in humans. My 
research has focus primarily on populations of opioid users (recreational prescription opioid users, chronic pain 
patients, and heroin users), but has also included populations of stimulant users. Many of my studies have 
examined the ability of medications (including naltrexone) to alter the abuse liability of addictive drugs.  Thus, I 
can attest to my ability to provide oversight for the proposed application. Dr. Jones, who has been a member of 
my laboratory for the last 7 years, has expertise in clinical laboratory studies of abuse liability, and is the 
burgeoning investigator in our division on addiction genetics (the focus of his K01 grant). I believe that the 
proposed studies are particularly exciting because they may reveal new information regarding how we test new 
medications for stimulant abuse.    
Publications most relevant to the current application: 
 
Askalsky P, Kalapatapu RK, Foltin RW, Comer SD. (2015) Butyrylcholinesterase levels and subjective 
effects of smoked cocaine in healthy cocaine users. Am J Drug Alcohol Abuse. 41(2):161-165. 
 
Comer SD, Mogali S, Saccone PA, Askalsky P, Martinez D, Walker EA, Jones JD, Vosburg SK, Cooper 
ZD, Roux P, Sullivan MA, Manubay JM, Rubin E, Pines A, Berkower EL, Haney M, Foltin RW. (2013) 
Effects of acute oral naltrexone on the subjective and physiological effects of oral D-amphetamine and 
smoked cocaine in cocaine abusers. Neuropsychopharmacology. 38(12): 2427-2438. 
 
Comer SD, Haney M, Foltin RW, Fischman MW. (1996) Amphetamine self-administration by humans: 
modulation by contingencies associated with task performance. Psychopharmacology (Berl). 127: 39-
46.Jones JD,  
 
Comer SD. (2015) A Review of Pharmacogenetic Studies of Drug Use Disorders. Drug and Alcohol 
Dependence, 152:1-14.  
B.  Positions and Honors 
Positions and Employment 
1993-present 
Research Scientist III-VI, Division on Substance Abuse, New York State Psychiatric Institute 
1993-2001 
Assistant Professor of Behavioral Biology, Dept. of Psychiatry, College of Physicians & 
Surgeons of Columbia University, New York, NY 
2001-2009 
Associate Professor of Clinical Neurobiology, Dept. of Psychiatry, College of Physicians & 
Surgeons of Columbia University, New York, NY 
Biosketches                                                                                                   Page 17
Contact PD/PI: Jones, Jermaine D


 
 
2009-present   
Professor of Clinical Neurobiology, Dept. of Psychiatry, College of Physicians & Surgeons of 
Columbia University, New York, NY 
Honors and Awards 
1987-1991 
University of Michigan Minority Merit Fellowship 
1990 
University of Michigan, Society for the Stimulus Properties of Drugs Young Investigator 
Travel Award 
1991-1992 
University of Michigan, Psychology Departmental Associate 
1991 
University of Michigan Doctoral Dissertation Fellowship 
1992 
University of Michigan, International Narcotics Research Conference Travel Award 
1993 
University of Minnesota, International Study Group Investigating Drugs as Reinforcers 
Student Paper Competition Award 
2004                     Joseph Cochin Young Investigator Award, College on Problems of Drug Dependence 
2015-2016  
 
President, College on Problems of Drug Dependence 
C.  Contribution to Science 
1. Assessing Medications to Treat Heroin and Prescription Opioid Abuse  
A primary focus of my laboratory has been to investigate potential treatment medications for opioid abuse 
and dependence using human laboratory models. The basic tenet of our Division’s model is that in order to 
determine the potential utility of a medication, its effects on drug-taking behavior must be studied directly. My 
research has investigated the effects of selective opioid receptor antagonists (naltrexone) and partial agonists 
(buprenorphine) on a range of opioid effects (self-administration, subjective ratings, and physiological 
measures). This research successfully demonstrated the clinical utility of these medications to antagonize the 
effects of heroin. 
 
Sullivan MA, Vosburg SK, Comer SD. (2006) Depot naltrexone: antagonism of the reinforcing, subjective, 
and physiological effects of heroin. Psychopharmacology (Berl). 189(1): 37-46. 
 
Comer SD, Walker EA, Collins ED. (2005) Buprenorphine/naloxone reduces the reinforcing and subjective 
effects of heroin in heroin-dependent volunteers. Psychopharmacology (Berl). 181(4): 664-675. 
Opioids present risks from both physiological (e.g., respiratory depression, physical dependence) and 
public health (e.g., individuals in pain) perspectives. Accordingly, my research has also focused on ways to 
decrease the abuse/misuse of opioid analgesics among patients under long-term opioid therapy to treat 
chronic pain. This research has identified factors and treatment strategies that may help prevent the 
development of abusive patterns of opioid use during pain treatment.  
 
Roux P, Sullivan MA, Cohen J, Fugon L, Jones JD, Vosburg SK, Cooper ZD, Manubay JM, Mogali S, 
Comer SD. (2013) Buprenorphine/naloxone as a promising therapeutic option for opioid abusing patients 
with chronic pain: reduction of pain, opioid withdrawal symptoms, and abuse liability of oral oxycodone. 
Pain. 154(8): 1442-1448. 
 
Comer SD, Sullivan MA, Vosburg SK, Kowalczyk WJ, Houser J. (2010) Abuse liability of oxycodone as a 
function of pain and drug use history. Drug Alcohol Depend 109(1-3): 130-138. 
2. Investigating Novel Pharmacological Approaches to Altering the Abuse Liability of Drugs 
More recently, my search for new pharmacotherapies has moved beyond opioid replacement and 
antagonism.  As the clinical utility of opioids is attributed to the same physiological effects responsible for their 
abuse potential, I have attempted to investigate novel targets to tease the two apart. This work has tested 
compounds targeting the NMDA receptors, along with various glial cell modulators. Though many compounds 
have shown modulatory effects, none have sufficiently attenuated the reinforcing or euphorigenic effects of 
opioids to show immediate clinical promise.  
 
Cooper ZD, Johnson KW, Pavlicova M, Glass A, Vosburg SK, Sullivan MA, Manubay JM, Martinez DM, 
Jones J.D., Saccone PA, Comer SD. (2015) The effects of ibudilast, a glial activation inhibitor, on opioid 
withdrawal symptoms in opioid-dependent volunteers. Addict Biol. doi: 10.1111/adb.12261. 
Biosketches                                                                                                   Page 18
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 
Cooper ZD, Jones JD, Comer SD. (2012) Glial modulators: a novel pharmacological approach to altering 
the behavioral effects of abused substances. Expert Opin Investig Drugs. 21(2): 169-178. 
 
Vosburg SK, Sullivan MA, Comer SD. (2011) Evaluation of the reinforcing and subjective effects of heroin 
in combination with dextromethorphan and quinidine. J Opioid Manag. 7(6): 451-461. 
 
Comer SD, Sullivan MA. (2007) Memantine produces modest reductions in heroin-induced subjective 
responses in human research volunteers. Psychopharmacology (Berl). 193(2): 235-245. 
3. Moving Towards a Better Understanding of Substance Abuse 
Another line of my research has examined the varying conditions that affect the abuse liability of opioids. 
These studies have systematically examined the relative abuse potential of several natural opiates (e.g., 
morphine) and synthetic opioids (e.g., heroin, oxycodone, and buprenorphine), via different routes of 
administration, among varying conditions (e.g., morphine-maintained, buprenorphine-maintained) and 
populations (e.g., Rx opioid users, normal healthy volunteers, chronic pain patients). This work has shown the 
nuanced nature of the abuse liability of opioids and provided clinicians with recommendations to mitigate risk, 
and investigators with recommendations to improve assessment.  
 
Comer SD, Metz VE, Cooper ZD, Kowalczyk WJ, Jones JD, Sullivan MA, Manubay JM, Vosburg SK, 
Smith ME, Peyser D, Saccone PA. (2013) Comparison of a drug versus money and drug versus drug self-
administration choice procedure with oxycodone and morphine in opioid addicts. Behav Pharmacol. 24(5-
6): 504-516. 
 
Comer SD, Sullivan MA, Vosburg SK, Manubay J, Amass L, Cooper ZD, Saccone P, Kleber HD. (2010) 
Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-
maintained intravenous heroin abusers. Addiction. 105(4): 709-718. 
 
Comer SD, Ashworth JB, Sullivan MA, Vosburg SK, Saccone PA, Foltin RW. (2009) Relationship between 
rate of infusion and reinforcing strength of oxycodone in humans. J Opioid Manag. 5(4): 203-212. 
 
Comer SD, Sullivan MA, Whittington RA, Vosburg SK, Kowalczyk WJ. (2008) Abuse liability of prescription 
opioids compared to heroin in morphine-maintained heroin abusers. Neuropsychopharmacology. 33(5): 
1179-1191. 
4. Understanding How Sex Impacts the Utility and Abuse Potential of Opioids.  
My colleagues and I have developed a laboratory model to investigate the responses to experimentally 
induced painful stimuli in men, normally-menstruating women, and women maintained on monophasic oral 
contraceptives. These studies have shown sex differences in sensitivity to pain, and demonstrated that some 
opioid medications are more effective and longer lasting in females.  
 
Manubay JM, Davidson J, Vosburg SK, Jones JD, Comer SD, Sullivan MS. (2015) Sex differences among 
opioid-abusing patients with chronic pain in a clinical trial. J Addiction Medicine. 9(1): 46-52. 
 
Comer SD, Cooper ZD, Kowalczyk WJ, Sullivan MA, Evans SM, Bisaga AM, Vosburg SK. (2010) 
Evaluation of potential sex differences in the subjective and analgesic effects of morphine in normal, 
healthy volunteers. Psychopharmacology (Berl). 208(1): 45-55. 
 
Kowalczyk WJ, Sullivan MA, Evans SM, Bisaga AM, Vosburg SK, Comer SD. (2010) Sex differences and 
hormonal influences on response to mechanical pressure pain in humans. J Pain. 11(4): 330-342. 
 
Kowalczyk WJ, Evans SM, Bisaga AM, Sullivan MA, Comer SD. (2006) Sex differences and hormonal 
influences on response to cold pressor pain in humans. J Pain. 7(3): 151-160. 
 
5. Contributing to the Development of Scientific Consensus on Important Drug Abuse Topics.   
It has been a long-held belief of mine that good science is a community effort. It begins with peer-review 
during the publication processes to ensure quality, followed by independent replication to ensure consistency, 
Biosketches                                                                                                   Page 19
Contact PD/PI: Jones, Jermaine D


 
 
and ends with a pool of credible data addressing a research question. From this existing body of scientific 
knowledge, consensus may begin to emerge. As an established investigator on drug abuse, I consider it my 
duty to contribute my knowledge and experience to panels attempting to best provide consensus 
recommendations concerning appropriate research methods and clinical management.   
 
Smith SM1, Dart RC, Katz NP, Paillard F, Adams EH, Comer SD, Degroot A, Edwards RR, Haddox JD, 
Jaffe JH, Jones CM, Kleber HD, Kopecky EA, Markman JD, Montoya ID, O'Brien C, Roland CL, Stanton M, 
Strain EC, Vorsanger G, Wasan AD, Weiss RD, Turk DC, Dworkin RH (2013) Analgesic, Anesthetic, and 
Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private 
partnership. Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION 
systematic review and recommendations. Pain. 154(11): 2287-2296. 
 
O'Connor AB, Turk DC, Dworkin RH, Katz NP, Colucci R, Haythornthwaite JA, Klein M, O'Brien C, Posner 
K, Rappaport BA, Reisfield G, Adams EH, Balster RL, Bigelow GE, Burke LB, Comer SD, Cone E, Cowan 
P, Denisco RA, Farrar JT, Foltin RW, Haddox JD, Hertz S, Jay GW, Junor R, Kopecky EA, Leiderman DB, 
McDermott MP, Palmer PP, Raja SN, Rauschkolb C, Rowbotham MC, Sampaio C, Setnik B, Smith SM, 
Sokolowska M, Stauffer JW, Walsh SL, Zacny JP. (2013) Abuse liability measures for use in analgesic 
clinical trials in patients with pain: IMMPACT recommendations. Pain 154(11): 2324-2234. 
 
Comer SD, Zacny JP, Dworkin RH, Turk DC, Bigelow GE, Foltin RW, Jasinski DR, Sellers EM, Adams EH, 
Balster R, Burke LB, Cerny I, Colucci RD, Cone E, Cowan P, Farrar JT, Haddox JD, Haythornthwaite JA, 
Hertz S, Jay GW, Johanson CE, Junor R, Katz NP, Klein M, Kopecky EA, Leiderman DB, McDermott MP, 
O'Brien C, O'Connor AB, Palmer PP, Raja SN, Rappaport BA, Rauschkolb C, Rowbotham MC, Sampaio 
C, Setnik B, Sokolowska M, Stauffer JW, Walsh SL (2012) Core outcome measures for opioid abuse 
liability laboratory assessment studies in humans: IMMPACT recommendations. Pain. 153(12): 2315-2324. 
 
Turk DC, O'Connor AB, Dworkin RH, Chaudhry A, Katz NP, Adams EH, Brownstein JS, Comer SD, Dart 
R, Dasgupta N, Denisco RA, Klein M, Leiderman DB, Lubran R, Rappaport BA, Zacny JP, Ahdieh H, Burke 
LB, Cowan P, Jacobs P, Malamut R, Markman J, Michna E, Palmer P, Peirce-Sandner S, Potter JS, Raja 
SN, Rauschkolb C, Roland CL, Webster LR, Weiss RD, Wolf K. (2012) Research design considerations for 
clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations. Pain 153(10): 1997-
2008. 
For my complete bibliography of 106 total career publications see: 
http://www.ncbi.nlm.nih.gov/pubmed/?term=comer+SD 
D. Research Support 
Ongoing Research Support: 
 
R21 DA040436- 01 (Comer)                                                                  07/15/2015 thru 07/30/2017 
NIDA 
Dynamic Contrast-enhanced MRI to Measure Blood-Brain Permeability in Substance Abusers 
This study will test if BBB permeability is directly correlated with increased magnitude of positive subjective 
responses, as well as methamphetamine self- administration.  
Role: Principal Investigator 
 
R01 DA035207-01A1 (Comer)  
 
 
 
 
 
 
 
 
 
 09/15/2014 thru 05/30/2019 
NIDA 
Risks and Benefits of Overdose Education and Naloxone Prescribing to Heroin Users 
This study assessed the impact of NYSDOH overdose education programs on opioid overdose in New York 
City along with way to improve the medical intervention among heroin users who witness an overdose event.   
Role: Principal Investigator 
 
U54 DA037842-01 (Levin)   
 
 
 
 
 
 
 
 
 
 
09/01/2014 thru 05/30/2019 
NIDA 
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Shared Pharmacotherapeutic Strategies for Cannabinoid and Opioid Use Disorders 
The goal of Project 3 is to examine a series of medications that may have utility in treating opioid use disorder, 
using our laboratory model and our decision algorithm to logically evaluate candidate medications to be tested 
in clinical settings. 
Role: PI of Project #3 
 
Protocol #6883R (Comer) 
 
01/01/2014 thru 09/30/2015 
Reckitt-Benckiser   
 
 
 
 
 
 
 
 
 
 
 
   
Reinforcing Effects of Intravenous Bup versus Bup/Nal in Hydromorphone-Maintained Heroin Users 
The purpose of the study is to evaluate the reinforcing effects of various intravenous doses of buprenorphine 
compared to buprenorphine/naloxone in heroin-dependent individuals  Intravenous heroin, naloxone, and 
placebo will be used as positive, negative, and neutral control conditions, respectively. 
Role: Principal Investigator 
 
Protocol #6817 (Comer)  
 
 
 
 
 
 
 
 
 
 
 
10/15/2013 thru 09/30/2015 
Marker-Test Diagnostics, Inc. 
The Utility of a Polyethylene Glycol Labeling Procedure for Identifying Fraudulent Urine Samples 
Role: Principal Investigator 
 
Protocol #6021(Comer)   
 
 
 
 
 
 
 
 
 
 
 
04/28/2007 thru 06/30/2015 
Avigen/MediciNova, Inc.  
 
 
 
 
 
 
 
 
 
 
 
 
The Safety, Tolerability and Preliminary Efficacy of AV411, a Glial Inhibitor, in Heroin Abusers  
AV411 was hypothesized to decrease withdrawal symptoms during the detoxification phase and is expected to 
increase the duration and magnitude of oxycodone-induced analgesia during laboratory sessions. 
Role: Principal Investigator 
 
Recently Concluded Support: 
 
R01 DA016759-10 (Comer) 
 
09/20/2003 thru 04/30/2015 
NIDA 
Prescription Opioid Effects in Drug and Non-drug Abusers 
This study examined the reinforcing, subjective, performance, and physiological effects of two commonly 
prescribed opioid medications (oxycodone, codeine) in two studies. 
Role: Principal Investigator 
R01 DA031022-03 (Comer & Bisaga) 
 
09/30/2010 thru 06/30/2014 
NIDA 
Pioglitazone for the Treatment of Opioid and of Nicotine Dependence 
The objective was to test the ability of pioglitazone, a peroxisome proliferator-activated receptor-gamma 
(PPARY) agonist to reduce abuse of heroin (Study 1), and cigarette smoking (Study 2).  
Role: Multi Principal Investigator 
P50 DA009236-20 (Kleber) 
 
09/30/1994 thru 05/31/2014 
NIDA 
 
Novel Medications Approaches for Substance Abuse 
Project 1: Laboratory Models: Pharmacotherapies for Opioid Dependence (PI: Comer) 
 
This aim of this project was to examine the ability of glial activation inhibitors (ibudilast and minocycline) and a 
peroxisome proliferator-activated gamma receptor (PPAR-gamma) agonist (pioglitazone) to alter the abuse liability 
of opioids. 
Role:  PI of Project #1 
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OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) 
BIOGRAPHICAL SKETCH 
Provide the following information for the Senior/key personnel and other significant contributors. 
Follow this format for each person.  DO NOT EXCEED FIVE PAGES. 
NAME: Mogali, Shanthi 
eRA COMMONS USER NAME (credential, e.g., agency login): SMogali 
 
POSITION TITLE: Instructor of Clinical Psychiatry 
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, 
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) 
INSTITUTION AND LOCATION 
DEGREE 
(if 
applicable) 
 
Completion 
Date 
MM/YYYY 
 
FIELD OF STUDY 
 
Fisk University: Nashville, TN 
B.A. 
1998-2001 
Biology 
Meharry Medical College: Nashville, TN 
M.D. 
2001-2005 
Medicine 
Emory University School of Medicine: Atlanta, GA 
Residency 
2005-2009 
Psychiatry 
Columbia University/ NYSPI: New York, NY 
Fellowship 
2009-2011 
Addiction Psychiatry 
 
 
 
 
 
A. Personal Statement 
 
 
I am a board certified addiction psychiatry physician and currently serve as an Instructor of Clinical Psychiatry at 
Columbia University that entails research, clinical and teaching roles. In 2009 I came to Columbia Medical 
Center as a research fellow in Dr. Levin’s T32 substance abuse fellowship and graduated in 2011. As a fellow, I 
expressed an interest in medication development for opioid dependence and began working closely with Dr. 
Sandra Comer in the Opioid Research Laboratory. Under Dr. Comer’s mentorship, I was awarded pilot funding 
through Dr. Kleber’s P50 Center grant to examine the physiological, subjective and analgesic effects of 
oxycodone-induced responses when combined with minocycline, a microglial inhibitor. These data have been 
analyzed and the manuscript is in progress. Currently, I am working with Dr. Comer and Dr. Jermaine Jones as 
the research psychiatrist for their ongoing opioid studies in the Opioid Research Laboratory. I also have a role in 
educating medical students, residents, and fellows in the diagnosis and treatment of substance abuse 
disorders. Overall, my goal is to actively contribute to the field of substance abuse research by examining novel 
medications that may deter drug abuse.  This grant, if funded, will allow us to evaluate for possible genetic 
modulation of the efficacy of naltrexone to attenuate the subjective and reinforcing effects of stimulant drugs. I 
will be responsible for the medical and psychiatric oversight, and ensuring the safety of our participants 
throughout screening and testing. Given my academic training, research among drug-abusing populations and 
history of productive collaborations with Drs. Jones, and Comer, I am in a strong position to help assure the 
successful completion of this project.  
 
Publications most relevant to the current application 
  
1. Comer, SD., Mogali, S., Saccone, PA., Askalsky, P., Martinez, D., Walker, E., Jones, JD., Vosburg, 
SK., Cooper, ZD., Roux, P., Sullivan, MA., Manubay, JM., Rubin, E., Pines, A., Berkower, EL., 
Haney, M., and Foltin, RW. (2013) Effects of acute oral naltrexone on the subjective and 
physiological effects of oral d-amphetamine and smoked cocaine in cocaine abusers. 
Neuropsychopharmacology. Jun 5: 1-12. PMCID: PMC3799062 
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Contact PD/PI: Jones, Jermaine D


 
 
 
2. Mogali, S., Jones, J.D., Manubay, J.M., Sullivan, M.A.,  & Comer S.D (2014) Effects of minocycline 
on oxycodone-induced responses in humans. Drug and Alcohol Dependence. July 1: e153. 
 
3. Jones, JD., Sullivan, MA., Vosburg, SK., Manubay, JM., Mogali, S., Metz, V., Comer, SD. (2014) 
Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-
maintained heroin users. Addict Biol. Jul 25. PMCID:  PMC4305506 
 
 
B. Positions and Honors 
 
Board Qualifications 
2011- Present  
General Psychiatry, American Board of Psychiatry and Neurology, Certificate No. 62563  
2012- Present  
Addiction Psychiatry, American Board of Psychiatry and Neurology, Certificate No. 2168  
 
Positions and Employment 
2009  
On call physician, Psychiatry Admissions, Georgia Regional Hospital, Georgia 
2009 
On call physician, Child and Adolescent Psychiatry, Gwinnett/Rockdale/Newton Crisis 
Stabilization Program, Georgia 
2009  
 
 
On call physician, Psychiatry Emergency Department Annex, Atlanta VA Hospital, Georgia 
2011- Present  
Instructor of Clinical Psychiatry, New York State Psychiatric Hospital, New York 
2011- Present  
Instructor of Clinical Psychiatry, Columbia University, New York 
2014- Present  
Medical Director, Center for Motivation and Change: Berkshires, Massachusetts 
 
Professional Memberships 
2007-2009  
 
Indo- American Psychiatric Association 
2007-2011  
 
American Psychiatric Association (APA)  
2009-2012  
 
College on Problems of Drug Dependence (CPDD): Associate Member 
 
Honors 
1998-2001 
 
Howard Hughes Research Scholar for Undergraduate Microbiology, Fisk University 
2002-2005 
Merit Based General Endowed Scholarship providing full tuition for Medical College 
Education 
2008   
 
      Indo-American Psychiatric Association Outstanding Resident Award Nominee 
2011                     Columbia University, Substance Abuse Division Pilot Study Grant: Funding Recipient 
2011  
 
      NIDA Director’s Travel Award, College on Problems of Drug Dependence  
 
C. Contribution to Science 
 
1. Extended-release injection naltrexone has proved promising in the treatment of opioid dependence. 
Treatment is often difficult as patients are not able to complete successful detoxification for induction onto 
agonist treatment. My most recent publication further investigated this problem by evaluating pre-treatment 
patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure 
prior to XR naltrexone treatment. These findings may be used to guide primary care providers to recognize 
appropriate patients for rapid naltrexone induction. I served as the primary author and conducted literature 
searches, designed the investigation, and gathered data for analysis. 
Mogali, S., Khan, NA., Drill ES., Pavlicova M., Sullivan, MA., Nunes ES., Bisaga, A. (2015) Baseline 
Characteristics of patients predicting suitability for rapid naltrexone induction. Am J Addict. April; 24: 
258-64. PMID: 25907815 
 
 
2. As a fellow, I expressed an interest in medication development for opioid dependence and began working 
closely with Dr. Sandra Comer in the Opioid Research Laboratory. Under Dr. Comer’s mentorship, I was 
Biosketches                                                                                                   Page 23
Contact PD/PI: Jones, Jermaine D


 
 
awarded pilot funding through Dr. Kleber’s P50 Center grant to examine the physiological, subjective and 
analgesic effects of oxycodone-induced responses when combined with minocycline, a microglial inhibitor. 
In brief, these data suggest that microglial inhibitors may play a role in deterring substance abuse by 
attenuating the subjective responses that may influence the abuse liability of oxycodone.  
 
Mogali, S. Jones, J.D., Manubay, J.M., Sullivan, M.A.,  & Comer S.D (2014) Effects of minocycline on 
oxycodone-induced responses in humans. Drug and Alcohol Dependence. July 1: e153. 
 
 
A complete list of my published work can be found at: 
http://www.ncbi.nlm.nih.gov/pubmed/?term=mogali+s 
 
D. Research Support 
Active 
 
U54 DA037842-01 (Levin) NIDA: 09/01/14 thru 06/30/19 
Shared Pharmacotherapeutic Strategies for Cannabinoid & Opioid Use Disorders 
 
Project 3: Laboratory: Pharmacotherapies for Opioid Use Disorder (PI: Comer) 
 
The goal of Project 3 is to examine a series of medications that may have utility in treating opioid use disorder, 
using our laboratory model and our decision algorithm to logically evaluate candidate medications to be tested 
in clinical settings. 
 
Role: Research Psychiatrist 
 
R01 DA035207-01A1 (Comer) NIDA: 09/15/14 thru 08/31/19 
Risks and Benefits of Overdose Education and Naloxone Prescribing to Opioid Abusers 
Fatal and nonfatal opioid overdoses have increased substantially in recent years. The current proposal seeks 
to evaluate a potential solution to this serious public health problem: namely, opioid overdose education and 
naloxone prescribing to substance abusers. Both a retrospective and a prospective study will be conducted to 
examine the risks and benefits of this novel approach. 
Role: Research Psychiatrist 
Completed 
 
R01 DA016759-09 (Comer) NIDA: 09/20/03 thru 04/30/15 
 
 
 
 
 
 
Prescription Opioid Effects in Drug and Non-drug Abusers 
This study will examine the reinforcing, subjective, performance, and physiological effects of two commonly 
prescribed opioid medications (oxycodone, codeine) in two studies. 
Role: Research Psychiatrist 
 
R01 DA031022-04 (Comer) NIDA: 09/30/10 thru 06/30/14 
 
 
Pioglitazone for Treatment of Opioid and Nicotine Dependence 
The objective is to test the ability of pioglitazone, a peroxisome proliferator-activated receptor-gamma     
(PPAR-gamma) agonist that is FDA-approved for use in the management of type 2 diabetes mellitus, to     
reduce abuse of heroin (Study 1), and cigarette smoking (Study 2). Pioglitazone will be tested in   
combination with buprenorphine/naloxone (Study 1) and with the nicotine patch (Study 2). 
Role: Research Psychiatrist 
 
P50 DA009236-20 (Kleber) NIDA: 09/30/94 thru 05/31/14 
 
Project 1: Laboratory Models: Pharmacotherapies for Opioid Dependence (PI: Comer) 
 
This aim of this project is to examine the ability of glial activation inhibitors (ibudilast and minocycline) and a 
peroxisome proliferator-activated gamma receptor (PPAR-gamma) agonist (pioglitazone) to alter the abuse liability 
of opioid medications. 
Role: Research Psychiatrist 
Biosketches                                                                                                   Page 24
Contact PD/PI: Jones, Jermaine D


BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person.  DO NOT EXCEED FIVE PAGES.
NAME
Henry R. Kranzler, M.D
eRA COMMONS USER NAME
henrykranzler
POSITION TITLE
Professor of Psychiatry 
EDUCATION/TRAINING  (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
Monmouth University, West Long Branch, NJ
B.A.
1976
Anthropology
Rutgers University, New Brunswick, NJ
M.A.
1980
Anthropology
UMDNJ, Robt. Wood Johnson Medical School, 
M.D.
1982
Medicine
Univ of CT School of Medicine, Farmington, CT
Residency
1986
Psychiatry
Univ of CT Alcohol Res Ctr, Farmington, CT
Post Doc.
1987
Alcohol Research
A.  Dr. Kranzler is an addiction psychiatrist whose research focuses on the genetics and pharmacological 
treatment of alcohol and drug dependence. The proposed project is a logical extension of work that he has 
done on the phararmacogenetics of substance dependence. For the past 4 years, he has served as a co-
mentor on Dr. Jones’ K01 pharmacogenetics grant and will serve as a consultant on the proposed project, 
meeting with Dr. Jones in person annually and through telephone meetings and email throughout the grant 
period. Dr. Kranzler will provide input on the implementation of the study, assisting in dealing difficulties that 
may arise, and in the analyses and report writing based on the research findings.  He will also be involved in 
planning and implementing any changes in design or procedures.  
Publications most relevant to the current proposal: 
1. O'Malley, S.S., Corbin, W.R., Leeman, R.F., DeMartini, K.S., Fucito, L.M., Ikomi, J., Romano, D.M., Wu, R., 
Toll, B.A., Sher, K.J., Gueorguieva, R., Kranzler, H.R. Reduction of alcohol drinking in young adults by 
naltrexone: a double-blind, placebo-controlled, randomized clinical trial of efficacy and safety. J Clin Psychiatry. 
e207-13. doi: 10.4088/JCP.13m08934. 2015.
 
2. Jones, J.D., Comer, S.D., & Kranzler, H.R. The Pharmacogenetics of Alcohol: A Critical Review. 
Alcoholism: Clinical and Experimental and Research, 39: 391-402, 2015.
3. Bi, J., Gelernter, J., Sun, J., Kranzler, H.R. Comparing the utility of homogeneous subtypes of cocaine use 
and related behaviors with DSM-IV cocaine dependence as traits for genetic association analysis. Am J Med 
Genet B Neuropsychiatr Genet.165B(2):148-56. 2015.
 
4. Chen, A.C., Morgenstern, J., Davis, .CM., Kuerbis, A.N., Covault, J., Kranzler, H.R,. Variation in Mu-Opioid 
Receptor Gene (OPRM1) as a Moderator of Naltrexone Treatment toReduce Heavy Drinking in a High 
Functioning Cohort. J Alcohol Drug Depend.1(1):101. 2013.
B. Positions and Honors.
1998–2010        Professor (with Tenure), Department of Psychiatry, Univ. of CT School of Medicine (UCSOM)
2010                  Professor, Department of Genetics and Developmental Biology, UCSOM
2010–present    Emeritus Professor of Psychiatry and Genetics and Developmental Biology, UCSOM
2010–present    Professor (with Tenure), Dept. of Psychiatry, University of Pennsylvania Perelman School of 
   Medicine (PSOM)
2013–present    Director, Center for Studies of Addiction, PSOM
Recent Honors:     2006  Frontiers of Science Lectureship, American Psychiatric Association
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Contact PD/PI: Jones, Jermaine D


                2007  Frank J. MacDonell Lectureship, Department of Psychiatry, University of Michigan 
     School of Medicine
    2008  Medical Sciences Graduate Students’ Association Lectureship, University of Calgary 
    2009  Distinguished Fellow, American Academy of Addiction Psychiatry
    2009  Fellow, American College of Neuropsychopharmacology
    2010  Alumnus of the Year, Monmouth University, West Long Branch, NJ
                              2013  Keynote Speaker, Visions in Pharmacology, University of Toronto
    2014  Editor-in-Chief, Alcoholism: Clinical and Experimental Research
    2014  James H. Tharp Award for Alcoholism Research (selected by the American Society of 
              Addiction Medicine)
    2014  Dan Anderson Award (selected by the Hazelden/Betty Ford Foundation)
 2015 Scott Mackler Award for Excellence in Substance Abuse Teaching, PSOM
Editorial Boards:
Addiction Biology
Addictive Disorders and Their Treatment
Drug and Alcohol Dependence
Experimental and Clinical Psychopharmacology
International Journal of Neuropsychopharmacology
C. Contributions to Science
1.  Dr. Kranzler’s contributions to science have been in three major areas: alcohol pharmacotherapy research; 
the identification or characterization of specific genes influencing the risk for dependence on alcohol and drugs; 
and genetic moderators of the response to the pharmacological treatment of alcohol use disorders.  His 
contributions to alcohol pharmacotherapy include the use of a targeted approach to opioid antagonist treatment 
and the development of long-acting naltrexone as a treatment option for alcohol dependence.  In 1994, 
naltrexone was approved by the U.S. Food and Drug Administration (FDA) to treat alcohol dependence.  Dr. 
Kranzler subsequently showed that the medication could be used on an “as needed” basis (Kranzler et al. 
1997) and completed two placebo-controlled trials comparing targeted with daily drug administration (Kranzler 
et al. 2003), the study design for which he shared with investigators at Biotie Therapies, a pharmaceutical 
company in Turku, Finland.  Their initial study of nalmefene using this approach led to the multi-center studies 
in the European Union that were the basis for the approval in 2012 of nalmefene by the European Medicines 
Agency.  Dr. Kranzler also pioneered the use of long-acting naltrexone to treat alcohol dependence (Kranzler 
et al. 1998; Kranzler et al. 2004) and was a major contributor to the multi-center trial of a long-acting 
formulation of the medication (Garbutt et al. 2005) that led to its approval in 2006 by the FDA to treat alcohol 
dependence.
1.  Kranzler, H.R., Tennen, H., Penta, C., Bohn, M.  Targeted naltrexone treatment in early problem 
drinkers.  Addictive Behaviors, 22:431-436, 1997.
2.  Kranzler, H.R., Modesto-Lowe, V., Nuwayser, E.S.  Sustained-release naltrexone for alcoholism 
treatment: A preliminary study.  Alcoholism: Clinical and Experimental Research, 22:1074-1079, 1998. 
3.  Kranzler, H.R., Armeli, S., Tennen, H., Blomqvist, O., Oncken, C., Petry, N., Feinn, R.  Targeted 
naltrexone for early problem drinkers.  Journal of Clinical Psychopharmacology, 23:294-304, 2003. 
4.  Garbutt JC, Kranzler HR, O’Malley SS, Gastfriend  DR, Pettinati  HM, Silverman  BL, Loewy  JW,  
Ehrich EW for the Vivitrex® Study Group.  Efficacy and tolerability of long-acting injectable naltrexone for 
alcohol dependence.  JAMA, 293:1617-1625, 2005.  
2.  Dr. Kranzler’s contributions to understanding the genetic basis of alcohol and drug dependence have 
included a series of candidate gene studies (e.g., Covault et al. 2004, 2008), linkage analyses (e.g., Gelernter 
et al. 2006), and genomewide association studies (e.g., Gelernter et al. 2014).  Current activity in this area 
includes a whole genome sequencing study focusing on cocaine dependence.  
1.  Covault, C., Gelernter, J., Hesselbrock, V., Nellissery, M., Kranzler, H.R.:  Allelic and haplotypic 
association of GABRA2 with alcohol dependence, American Journal of Medical Genetics (Neuropsychiatric 
Genetics), 129B:104-109, 2004.
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Contact PD/PI: Jones, Jermaine D


2.  Covault J, Gelernter J, Jensen K, Anton R, Kranzler HR.  Markers in the 5′ region of GABRG1 
associate to alcohol dependence and are in linkage disequilibrium with markers in the adjacent GABRA2 
gene, Neuropsychopharmacology, 33:837-848, 2008.  (PMCID: PMC2743531)
3.  Gelernter J, Panhuysen C, Wilcox M, Hesselbrock V, Rounsaville B, Poling J, Weiss R, Sonne S, Farrer 
L, Kranzler HR:  Genomewide linkage scan for opioid dependence and related traits.  American Journal of 
Human Genetics, 78:759-769, 2006.  (PMCID: PMC1474044)
4.  Gelernter J, Kranzler HR, Sherva R, Almasy L, Koesterer R, Anton R, Preuss UW, Ridinger M, Rujescu 
D, Wodarz N Zill P, Han S, Zhao H, Farrer LA.  Genome-wide association study of alcohol dependence: 
significant findings in African- and European-Americans including novel risk loci, Molecular Psychiatry, 
19:41-49, 2014. (PMCID: PMC24166409)
3.  Dr. Kranzler’s most recent work has focused on topiramate, a glutamate antagonist with demonstrated 
efficacy in the treatment of alcohol dependence.  He and colleagues found that the medication is efficacious 
only in a subgroup of individuals who are homozygous for an allele of rs2832407 in the GRIK1 gene, which 
encodes a kainate receptor subunit.  The specific single nucleotide polymorphism that moderates the response 
to topiramate treatment was identified through association to alcohol dependence (Kranzler et al. 2009) and 
shown to be a significant pharmacogenetic predictor of reductions in heavy drinking (Kranzler et al. 2014a).  
Most recently, we found persistent effects of topiramate in rs2832407*C-allele homozygotes during a six-month 
post-treatment follow-up period (Kranzler et al. 2014b) and evidence that the effects of topiramate on heavy 
drinking in the genotype-responsive group are mediated by self-efficacy to resist heavy drinking (Kranzler et al. 
2014c).  
1. Kranzler HR, Gelernter J, Anton RF, Arias AJ, Herman A, Zhao H, Burian L, Covault J:  Association of 
markers in the 3’ region of the GluR5 kainate receptor subunit gene (GRIK1) to alcohol dependence.  
Alcoholism: Clinical and Experimental Research, 33:1–6, 2009.  (PMID: 19320626; PMCID: PMC2772659) 
2. Kranzler HR, Covault J, Feinn R, Armeli S, Tennen T, Arias AJ, Gelernter J, Oncken C, Pond T, 
Kampman KM.  Topiramate treatment for heavy drinkers: Moderation by a GRIK1 polymorphism, American 
Journal of Psychiatry, 171: 445-452, 2014a. (PMCID: PMC3997125)
3. Kranzler HR, Wetherill R, Feinn R, Pond T, Gelernter J, Covault J. Posttreatment effects of topiramate 
treatment for heavy drinking, Alcoholism: Clinical and Experimental Research 38:3017-23, 2014b. (PMCID: 
PMC4293099)
4.  Kranzler HR, Armeli, Wetherill R, Feinn R, Tennen H, Gelernter J, Covault J, Pond T.  Self-efficacy 
mediates topiramate-induced reduction of drinking, which is moderated by GRIK1 genotype.  Addiction 
Biology, 2014c Dec 15 [Epub ahead of print].
For a full list of Dr. Kranzler’s publications, which include 362 articles (published or in press), a full 
listing of which is at http://www.ncbi.nlm.nih.gov/pubmed/?term=kranzler+hr
D. Research Projects Ongoing:
R01 AA017535 (Gelernter/Kranzler)
      9/15/09 - 8/31/15
NIH/NIAAA
(NCE)
Genetics of Alcohol Dependence in African-Americans
The purpose of this proposal is to identify specific risk genes in African-Americans that contribute to the 
development of alcohol dependence.  Dr. Kranzler directs the UPenn site and oversees phenotypic 
assessment across both the Yale and UPenn sites.
R01 DA030976 (Wilhelmsen/Kranzler) 
          9/30/10 – 5/31/16
NIH/NIDA
          (NCE)
Deep sequencing studies for cannabis and stimulant dependence
 
The purpose of this study is to conduct deep sequencing of existing DNA and refinement of phenotypic 
information to enhance gene finding efforts for cannabis, methamphetamine, and cocaine dependence.  Dr. 
Biosketches                                                                                                   Page 27
Contact PD/PI: Jones, Jermaine D


Kranzler oversees analyses related to subtypes of cocaine dependence as phenotypes and will participate in 
the analysis of the sequence data.
R01 AA021164 (Kranzler)
NIH/NIAAA
 4/1/12 – 3/31/17
2/2 Pharmacogenetic Treatment for Alcoholism
This study examines genetic variants as moderators of the response to ondansetron treatment of alcohol 
dependence.  It is a collaborative R01 being conducted at two sites: the University of Pennsylvania and the 
University of Maryland.  
R01 DA012690 (Gelernter)
8/5/00 – 8/31/18
NIH/NIDA
Genetics of Opioid Dependence
Risk for opioid dependence is influenced by genes. The main object of this study is to find genes that influence 
risk for opioid dependence by sequencing the entire exome (the part of the genome that is known to serve a 
coding function), in groups of people who are of European or African ancestry, with and without opioid 
dependence.
Research Grant (McKay)
4/1/14 – 3/31/19
Department of Defense
Preventing risky drinking in veterans treated with prescription opioids
The major goals of this project are: 1) To compare the effectiveness of a 12-month integrated prevention 
intervention with standard care over an 18-month follow-up period, for veterans treated with prescription 
opioids and who are engaging in risky/hazardous drinking, as defined by NIAAA guidelines; and 2) To examine 
secondary outcome measures, moderator effects, and mediation effects.
R01 CA184315 (Kranzler)
8/15/14 – 7/31/19
NIH/NCI
Placebo-controlled trial of bupropion for smoking cessation in pregnant women
The major goals of this project are: 1) conduct a 10-week placebo-controlled trial of bupropion 300 mg/day in 
360 pregnant smokers who are at 13–24 weeks gestation and generally from low-income, under-served 
communities; 2) assess changes in depression symptoms and craving as mediators of bupropion’s effect on 
quit rates; and 3) explore genetic, metabolic, and social/behavioral moderators of the efficacy of bupropion on 
cigarette abstinence and safety.
R01 AA023192 (Kranzler)
8/15/14 – 7/31/19
NIH/NIAAA
Pharmacogenetic Analysis of Topiramate Treatment of AUD
The major goals of this project are: 1) To examine the moderating effect of rs2832407 in GRIK1 on the efficacy 
of topiramate 200 mg/day in reducing the frequency of heavy drinking; and 2) To examine daily processes, 
including expectancies regarding the positive effects of drinking and their interaction with genotype and 
medication group, to predict the intensity of nighttime drinking.
COMPLETED (PAST 3 YEARS)
R01 AA011330 (Gelernter/Kranzler) 
NIH/NIAAA 
3/1/09 – 2/28/15
Genetics of Alcohol Dependence in American Populations 
Biosketches                                                                                                   Page 28
Contact PD/PI: Jones, Jermaine D


The purpose of this proposal is to identify genes predisposing to alcohol dependence. It involves recruitment of 
a sample of alcohol-dependent cases and screened controls. Dr. Kranzler directs the UPenn site and oversees 
phenotypic assessment across both the Yale and UPenn sites.
K24 AA13736 (Kranzler)
4/01/08 – 9/30/14
NIH/NIAAA
Novel Approaches to Alcoholism Pharmacotherapy and Risk
Midcareer Investigator Award in Patient-Oriented Research 
This Mid-Career Investigator Award (K24) enabled Dr. Kranzler to mentor beginning clinical investigators, 
continue his career development, and conduct research on the pharmacotherapy of alcoholism and the 
genetics of alcohol and drug dependence. 
P60 AA03510 (Hesselbrock)
12/1/07 - 11/30/12
NIH/NIAAA
Center for Research on the Etiology and Treatment of Alcohol Dependence
The focus of this center is on the systematic exploration of the alcohol dependence syndrome, including its 
etiology, patterning and treatment.  Dr. Kranzler serves as Principal Investigator of a component of the center, 
entitled “Topiramate Treatment of Heavy Drinkers.”  
Biosketches                                                                                                   Page 29
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date:
2015-07-15T14:35:23.000-04:00
PHS 398 Cover Page Supplement
OMB Number: 0925-0001
1. Project Director / Principal Investigator (PD/PI)
Prefix:
Dr.
First Name*:
Jermaine
Middle Name:
D
Last Name*:
Jones
Suffix:
 
2. Human Subjects
Clinical Trial?
●
No
❍
Yes
Agency-Defined Phase III Clinical Trial?*
●
No
❍
Yes
3. Permission Statement*
If this application does not result in an award, is the Government permitted to disclose the title of your proposed project, and the name,
address, telephone number and e-mail address of the official signing for the applicant organization, to organizations that may be
interested in contacting you for further information (e.g., possible collaborations, investment)?
❍
Yes
●
No
4. Program Income*
Is program income anticipated during the periods for which the grant support is requested?
❍
Yes
●
No
If you checked "yes" above (indicating that program income is anticipated), then use the format below to reflect the amount and source(s).
Otherwise, leave this section blank.
Budget Period*
Anticipated Amount ($)*
Source(s)*
 
   
 
   
 
   
 
   
 
   
                                                                                                              Page 30
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date:
2015-07-15T14:35:23.000-04:00
PHS 398 Cover Page Supplement
5. Human Embryonic Stem Cells
Does the proposed project involve human embryonic stem cells?*
●
No
❍
Yes
If the proposed project involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following
list: http://grants.nih.gov/stem_cells/registry/current.htm. Or, if a specific stem cell line cannot be referenced at this time, please check the box
indicating that one from the registry will be used:
Cell Line(s):
  
Specific stem cell line cannot be referenced at this time. One from the registry will be used.
6. Inventions and Patents (For renewal applications only)
Inventions and Patents*:
❍
Yes
❍
No
If the answer is "Yes" then please answer the following:
Previously Reported*:
❍
Yes
❍
No
7. Change of Investigator / Change of Institution Questions
❏
Change of principal investigator / program director
Name of former principal investigator / program director:
Prefix:
 
First Name*:
 
Middle Name:
 
Last Name*:
 
Suffix:
 
❏
Change of Grantee Institution
Name of former institution*:
 
                                                                                                              Page 31
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date: 2015-07-15T14:35:23.000-04:00
OMB Number: 0925-0001
PHS 398 Modular Budget
Budget Period: 1
Start Date: 04/01/2016     End Date: 03/31/2017
A. Direct Costs
Funds Requested ($)
Direct Cost less Consortium F&A*
150,000.00
Consortium F&A
0.00
Total Direct Costs*
150,000.00
B. Indirect Costs
Indirect Cost Type
Indirect Cost Rate (%)
Indirect Cost Base ($)
Funds Requested ($)
1.
Modified TDC
62.00
150,000.00
93,000.00
2.
 
 
 
 
3.
 
 
 
 
4.
 
 
 
 
Cognizant Agency
(Agency Name, POC Name and Phone Number)
DHHS, Ryan McCarthy, (212) 264-2069
Indirect Cost Rate Agreement Date
01/15/2015
Total Indirect Costs
93,000.00
C. Total Direct and Indirect Costs (A + B)
Funds Requested ($)
243,000.00
                                                                                                              Page 32
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date: 2015-07-15T14:35:23.000-04:00
PHS 398 Modular Budget
Budget Period: 2
Start Date: 04/01/2017     End Date: 03/31/2018
A. Direct Costs
Funds Requested ($)
Direct Cost less Consortium F&A*
125,000.00
Consortium F&A
0.00
Total Direct Costs*
125,000.00
B. Indirect Costs
Indirect Cost Type
Indirect Cost Rate (%)
Indirect Cost Base ($)
Funds Requested ($)
1.
Modified TDC
62.00
125,000.00
77,500.00
2.
 
 
 
 
3.
 
 
 
 
4.
 
 
 
 
Cognizant Agency
(Agency Name, POC Name and Phone Number)
DHHS, Ryan McCarthy, (212) 264-2069
Indirect Cost Rate Agreement Date
01/15/2015
Total Indirect Costs
77,500.00
C. Total Direct and Indirect Costs (A + B)
Funds Requested ($)
202,500.00
                                                                                                              Page 33
Contact PD/PI: Jones, Jermaine D


Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date: 2015-07-15T14:35:23.000-04:00
PHS 398 Modular Budget
Cumulative Budget Information
1. Total Costs, Entire Project Period
Section A, Total Direct Cost less Consortium F&A for Entire Project Period ($)
275,000.00
Section A, Total Consortium F&A for Entire Project Period ($)
 
Section A, Total Direct Costs for Entire Project Period ($)
275,000.00
Section B, Total Indirect Costs for Entire Project Period ($)
170,500.00
Section C, Total Direct and Indirect Costs (A+B) for Entire Project Period ($)
445,500.00
2. Budget Justifications
Personnel Justification
Jones_R21_Just_7_15_15.pdf
Consortium Justification
 
Additional Narrative Justification
Jones_Additional Narrative Justification.pdf
                                                                                                              Page 34
Contact PD/PI: Jones, Jermaine D


Budget Justification 
 
The Research Foundation for Mental Hygiene/New York State Psychiatric Institute (RFMH/NYSPI) 
implemented a new policy governing the proposing of effort for those investigators who possess an 
appointment at RFMH/NYSPI and an academic appointment at the University and an academic appointment at 
Columbia University (“Joint Appointees”). Joint Appointees previously proposed their effort on RFMH/NYSPI 
projects based on a percentage of their total professional effort across Columbia University and RFMH/NYSPI, 
on an integrated basis. As of Spring 2014, RFMH/NYSPI has transitioned to a new model based upon the 
method utilized by those with joint Veterans Affairs/academic appointments*.  Under the new model, Joint 
Appointees propose their effort on RFMH/NYSPI projects based on a percentage of their RFMH/NYSPI effort 
only. However, for informational purposes, the budget justification also will indicate what the effort would be if it 
were calculated based on total professional effort (TPE) across both institutions.  
 
* As described in the NIH Guide for Grants and Contracts, vol. 18, no. 27, August 11, 1989. 
 
 
PERSONNEL 
 
Jermaine D. Jones, Ph.D., Principal Investigator: (1.20 cal months, Yrs 1-2, no salary requested until 
6/1/2016). Dr. Jones is a Research Scientist IV at the Research Foundation for Mental Hygiene, Inc. (RFMH) 
as well as an Assistant Professor of Clinical Neuroscience in the Department of Psychiatry’s Division on 
Substance Abuse at Columbia University’s College of Physicians and Surgeons.  Dr. Jones is currently the 
recipient of a K01 award from NIDA entitled: “Contribution of Various Genetic Polymorphisms to Oxycodone’s 
Abuse Liability”.  He received his Ph.D. in the summer of 2008 and began his 3-year fellowship in the Division 
on Substance Abuse in the fall of 2008. He has been working with Dr. Comer since he began his fellowship 
and has become proficient at conducting abuse liability assessments in clinical populations, and is a 
developing researcher on the genetics of addiction. Dr. Jones will assume all scientific responsibility for the 
study.  Currently, Dr. Jones has a K01 award (K01 DA030446) that ends on 5/31/2016; he will be paid salary 
beginning 6/1/2016.  From 4/1/2016 thru 5/31/2016, Dr. Jones’ effort on this grant will be subsumed by his K 
award.  The effort listed by Dr. Jones in this submission is based solely upon his effort at RFMH. 
 
Sandra D. Comer, Ph.D., Co-Investigator: (TPE: 0.22 cal months, Yrs 1-2; RFMH/NYSPI Effort: 0.36 cal 
months,).  Dr. Comer is a Research Scientist VI at the Research Foundation for Mental Hygiene, Inc. (RFMH), 
a Research Scientist 5 at the New York State Psychiatric Institute (NYSPI), as well as a Professor of Clinical 
Neurobiology at Columbia University’s College of Physicians and Surgeons.  She has been performing 
substance abuse research with humans for over 20 years and has over 25 years research experience working 
with opioids. Dr. Comer will supervise Dr. Jones concerning the scientific aspects of the study, data analysis 
and manuscript writing.  The effort listed by Dr. Comer in this submission is based upon her effort at 
RFMH/NYSPI.  If the effort were figured based on Dr. Comer’s total professional effort at RFMH/NYSPI and 
Columbia University it would be 0.22 cal months effort.   
 
Shanthi Mogali, M.D., Co-Investigator: (0.60 cal months, Yrs 1-2). Dr. Mogali is a board certified Addiction 
Psychiatry physician and Technical Specialist III at the Research Foundation for Mental Hygiene, Inc.  She is 
also an Instructor in Clinical Psychiatry in the Division on Substance Abuse at Columbia University’s College of 
Physicians and Surgeons.  She has over 10 years of psychiatric clinical experience and has worked with Drs. 
Jones and Comer since joining the Division on Substance Abuse in 2009.  Dr. Mogali will oversee clinical 
assessment during screening, medical supervision of the laboratory sessions and assessment/reporting of 
adverse events.  The effort listed by Dr. Mogali in this submission is based solely upon her effort at RFMH. 
 
Janet Murray, N.P., Research Nurse (1.20 calendar months, Yrs 1-2): Janet Murray has been with the Division 
of Substance abuse for 10 years and has worked with both the Cocaine and Opioid research units. Having 
worked with Drs. Jones and Comer for over 8 years, Ms. Murray is very familiar with the behavioral observation 
techniques and laboratory procedures involved in clinical laboratory studies.  She will be responsible for 
various aspects of medical screening of potential participants, along with administering study drug, and safety 
monitoring during laboratory session. The effort listed for Ms. Murray in this submission is based solely upon 
her effort at RFMH. 
Personnel Justification                                                                                       Page 35
Contact PD/PI: Jones, Jermaine D


 
 
Rachel Luba, B.A., Research Assistant: (11.00 cal months, Yrs 1-2).  Ms. Luba is a Research Support 
Assistant II at the Research Foundation for Mental Hygiene (RFMH) and has been with the Division on 
Substance Abuse for 2 years and has been trained in: participant recruitment, data management and 
behavioral observation techniques by Drs. Jones and Comer.  On the upcoming project, she will be 
responsible for scheduling participant visits, performing assessments, and managing data collection from the 
laboratory sessions. The effort listed by Ms. Luba in this submission is based solely upon her effort at RFMH. 
 
The fringe rate at the Research Foundation for Mental Hygiene, Inc. (RFMH) is 35%.  The IDC rate at RFMH is 
calculated at 62% of modified total direct costs (MTDC).  Except where specifically noted, a 3% cost of living 
increase is assumed for all salary expenses except where individuals have reached the NIH salary cap.  The 
Research Foundation for Mental Hygiene operates on an April 1st thru March 31st fiscal year and has 
institutionally mandated cost of living salary increases on April 1st of each year.  All salary figures presented in 
the budget reflect these cost of living adjustments 
 
CONSULTANT 
Henry Kranzler, M.D.: Dr. Kranzler is currently a Professor of Psychiatry and Director of the Center for Studies 
of Addiction at the Univ. of Pennsylvania, Perelman School of Medicine. He has served as principle 
investigator or co-investigator on over 12 NIDA- or NIAAA-funded studies investigating genetic contribution to 
drug use disorders. He has also co-authored over 110 publications related to the study of addiction genetics.  
In addition to frequent electronic communications, in person meetings between Dr. Jones and Dr. Henry 
Kranzler are anticipated to occur once every three months.  We have budgeted $500 per visit for Dr. Kranzler’s 
honoraria and are requesting $2,000 per year for Yrs 1-2 (4 visits per year @ $500/visit (5 hours @ $100/hr = 
$500)) = $2,000 per year).  Dr. Kranzler currently serves as the Co-mentor on Dr. Jones’ K01 grant, and 
formerly functioned as an advisor on the NYSPI Division on Substance Abuse recently completed Center Grant 
(P50 DA009236-20). 
 
PARTICIPANT FLOW 
Over the proposed 2-year funding period, approximately 70 participants will be enrolled (based on previous 
inpatient studies of this duration we anticipate a negligible dropout rate). Approximately 10 participants will be 
enrolled during each 3-month period (average 35 participants per year).The final 3 months of the funding 
period will be devoted to data analysis and publication. 
 
SUPPLIES 
Study Supplies: Based upon our previous investigations we anticipate needing $10 for each participant to 
purchase supplies such as: paper, case books, syringes, Band-Aids, alcohol wipes, gloves, etc. Therefore we 
have requested $350 per year for study supplies (35 participants per year x $10/participant).  
 
Urine Toxicology Tests: Urine testing will be performed at each screening visit for all potential study 
participants to assess for recent drug use. We are requesting $420 each year for urine toxicology tests.  The 
breakdown for each year is as follows: $4 per test, 3 tests per participant x 35 screened participants/yr).  
 
Pharmacy Medication Expense: Medications will be prepared and stored in the Research Pharmacy at NYSPI.  
Over the life of the study, we will need to purchase:  Naltrexone 50mg – 5 bottles @ $19.52/bottle = $97.60; 
and Methamphetamine – 21 bottles @ $304.77/bottle = $6,400.17, for a total of $6,497.77.  Therefore, we are 
requesting $3,248.89 per year to cover the cost of medication.  Per the NYSPI pharmacy directive, the costs 
for Administrative Expenses will increase at 4% per year in Year 2. 
 
TRAVEL 
PI Travel Expenses: The results of this study will be of interest to many in the field of substance abuse 
research and treatment. Therefore we are requesting $2,500 to cover the cost of travel, food and lodging for 
the primary investigator to attend the annual meeting of the College of Problems on Drug Dependence or the 
International Behavior and Neural Genetics Society.                                              
Personnel Justification                                                                                       Page 36
Contact PD/PI: Jones, Jermaine D


 
OTHER EXPENSES 
 
Pharmacy Administrative Fees: In addition to the cost of medications (see SUPPLIES above), the NYSPI 
pharmacy charges us for: a yearly administrative fee ($600/yr), the manufacturing of capsules ($52.50/yr) and 
for prescription dispensing ($15.63/Rx, 10 Rx’s per participant, 35 participants/yr = $5,470.50).  Therefore, we 
are requesting $6,123 per year for pharmacy administrative expenses.  Per the NYSPI pharmacy directive, the 
costs for Administrative Expenses will increase at 4% per year in Year 2. 
 
Volunteer Compensation: requesting $2,625 + $19,250 = $21,875 per year (see below) 
 
Screenings:  Participants will receive $25 for each of the three screening assessments. Based upon 
previous efforts to recruit this participant population, we anticipate needing to screen approximately 80 
potential study candidates over 2 years to obtain our target N.  So for each year we are requesting 
$2,625 for screenings: ($25 x 3 screening visits x 35 participants per year = $2,625). 
 
Laboratory sessions: Those volunteers who are enrolled in the laboratory testing will earn between $25-
$50 per day [$50 per day if they complete all 5 session ($25/day completion incentive)].  Participants 
also have the option of earning up to $18 during each self-administration session (i.e., via drug vs 
money procedure).   There are a number of factors involved in estimating the cost associated with this 
portion of the study (e.g., # enrolled vs completers, drug vs. money preference etc. etc.,) however, we 
estimate the total payment to be ≈$550 per participant x 35 enrolled participants/yr= $19,250. 
 
DNA Isolation:  In order to conduct analyses on the genetic polymorphisms of interest, we will extract DNA 
from blood samples collected from all study participants.  The Columbia University Medical Center has a 
Human Genetics Resources Core that will isolate the DNA at a cost of $45 per sample.  We will store these 
samples in our -20C freezer.  Thus, we are requesting $1,575 per year to extract DNA from our blood samples 
(35 participants per year x $45). 
 
DNA Analysis: Blood samples collected from all study participants will be assessed for the alleles of interest at 
a cost of approximately $10 per sample. Therefore, we are requesting $350 per year to fund genotyping 
expenses (35 participants per year x $10 per sample). 
 
Advertising/Recruitment: In order to obtain participants we plan to advertise this study in three journals that 
have proven to be the most effective in our previous recruitment efforts (AM New York, The Village Voice and 
the New Jersey Journal). We plan to post an ad in one of the 3 journals every other week through the funding 
period weeks on and off throughout the duration of the study. We will also utilize free recruitment sources such 
as craigslist.org and researchmatch.org. We are requesting $11,105 for both years for advertising expense.   
 
Personnel Justification                                                                                       Page 37
Contact PD/PI: Jones, Jermaine D


Additional Narrative Justification
Though our anticipated Direct Cost expenses for Y1 ($133,575.78) and Y2 
($141,423.69) are very similar, we will be requesting (6) six modules of $25,000 
each in Y1 ($150,000) and (5) five modules of $25,000 each in Y2 ($125,000) in 
order to be in compliance with the funding limits of the R21 award. 
Additional Narrative Justification                                                                            Page 38
Contact PD/PI: Jones, Jermaine D


              
PHS 398 Research Plan
Please attach applicable sections of the research plan, below.
OMB Number: 0925-0001
Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date:
2015-07-15T14:35:23.000-04:00
1. Introduction to Application
(for RESUBMISSION or REVISION only)
 Introduction to revised application 7-15-15.pdf
2. Specific Aims
 SpecificAims 7-15-15.pdf
3. Research Strategy*
 Research Strategy 7-15-15.pdf
4. Progress Report Publication List
 
Human Subjects Sections
5. Protection of Human Subjects
 Protection of Human Subjects 7-15-15.pdf
6. Inclusion of Women and Minorities
 Inclusion of Women and Minorities 7-15-15.pdf
7. Inclusion of Children
 Inclusion of Children 7-15-15.pdf
Other Research Plan Sections
8. Vertebrate Animals
 
9. Select Agent Research
 
10. Multiple PD/PI Leadership Plan
 
11. Consortium/Contractual Arrangements
 
12. Letters of Support
 Letter of Support_Kranzler_1.pdf
13. Resource Sharing Plan(s)
 Data Sharing Plan 7-14-15.pdf
Appendix (if applicable)
14. Appendix
SCID.pdf
BDI.pdf
CGI.pdf
DAST.pdf
TSR.pdf
MEDICAL HISTORY QUESTIONNAIRE.pdf
Intake Questionnaire.pdf
Substance Use Inventory.pdf
RAB.pdf
Self-Report ASI_1.pdf
                                                                                                              Page 39
Contact PD/PI: Jones, Jermaine D


 
INTRODUCTION TO THE REVISED APPLICATION 
This is a resubmission of the R21 application entitled Using Pharmacogenetics to Better Evaluate 
Naltrexone for Treating Stumulant Abuse. Overall, the committee was very positive and noted several strengths of 
each component of the grant including: “outstanding environment,” “clinically significant” area of study and 
“innovative” research plan. The committee also noted several areas needing improvement and clarification. This 
letter only addresses the major points of criticism; however, each individual critique has been addressed.  
Critiques of the Investigators:  Reviewers raised concern that none of the research team has significant 
human genetics research experience/publication history and that data from my currently funded 
pharmacogenetics grant would make the reviewers “more confident”. Response: To address this concern, I have 
added Dr. Hank Kranzler as a paid consultant on the grant. Dr. Kranzler has served as the principle investigator or 
co-investigator on over 12 NIDA/NIAAA- funded studies investigating genetic contribution to the abuse and 
treatment of substance use disorders and has authored over 110 publications related to the study of addiction 
genetics. Dr. Kranzler currently serves as the co-mentor or my K01 grant (DA030446) Contribution of Various 
Genetic Polymorphisms to the Abuse Liability of Oxycodone.  In addition to agreeing to assist in the successful 
completion of the proposed study, Dr. Kranzler has lent his expertise to revising the research plan based on the 
initial grant review. Since the original submission, I have also significantly improved my pharmacogenetics 
authorship with publications in Drug and Alcohol Dependence, and Alcoholism: Clinical and Experimental 
Research. I have also submitted data from my K01 study for publication, this data also served as preliminary data 
for a pharmacogenetics R01 grant submission (DA040906) on which I was principal investigator. 
Critique of the Research Plan: Concerning the research plan, the reviewers were concerned that the 
inclusion criteria related to (ab)use of psychostimulants was too broad, and would lead to significant 
variability in subjective response to the study’s challenge drug and the relative value of the drug to the alternative 
monetary reinforcer,  confounding both assessments of abuse liability.  Response: To address this concern, the 
investigators decided to modify the target study sample to individuals with more severe and current abuse of 
psychostimulant drugs (i.e., meet current DSM-V criteria for moderate-to-severe stimulant use disorder, specifically 
cocaine or amphetamines, yet are NOT seeking treatment for their drug use). Accordingly, to match these 
participants with more stimulant abuse experience, we have changed the test drug and route of administration. We 
will now test naltrexone’s (NTX) ability to attenuate the self-administration and positive subjective experience of 
intranasally administered methamphetamine (M-AMPH, 50mg/70kg). We have significant experience testing this 
population and this drug/route in our clinical laboratory procedures, and are confident that among this new 
population there will be significantly less variability in the effects of the IN test drug. Additionally, the current route of 
administration better models how amphetamines and other stimulants are abused in the real world (vs. the oral 
administration that all previous NTX+AMPH lab studies have used).  
Our experience in testing potential medication effects under these specific subject and dosing parameters 
has also allowed us to carefully select an appropriate monetary alternative reinforcer to test the drug against. 
Therefore, we are confident that data we obtain on the ability of NTX to shift participants’ responding from drug 
reinforcer to the monetary reinforcer will have predictive validity of its treatment potential. This addresses another of 
the reviewers’ concerns that findings in these clinical laboratory setting may not translate to treatment 
potential in the real world. Laboratory models of self-administration synthesize the physiological, behavioral, and 
cognitive aspects of a drug’s effects, and translate them into a quantifiable indicator of abuse liability, drug-taking 
behavior itself. In general, drugs of abuse are thought of as reinforcers, because they produce rewarding subjective 
feelings thereby increasing the likelihood/occurrence of the behavior(s) that lead to their delivery (Catania, 1971; 
Brady and Lucas, 1984). Within the context of self-administration clinical studies, the abuse potential of a drug have 
typically been quantified in terms of: ratings of “liking” and/or “good drug effect,” the amount of effort they are willing 
to devote to receive the drug, and/or the choice of drug vs. a nondrug alternative reinforcer. Data from our lab and 
many others has shown the value of human self-administration procedures in the development of treatment 
medications for substance abuse, and demonstrated their predictive validity (Carpenter et al., 2009; Comer et al., 
2008; Jones et al., 2013). 
Finally, the reviewers were conflicted as to whether a design approach that studies a single possible 
genetic moderator, or one that investigates several, would be the most clinically meaningful. As such, the 
new study design is capable of doing both. Response: While the moderating effect of the OPRM1 A118G SNP 
(rs1799971) remains the primary target (because interaction with NTX has been the substantiated by other studies), 
in order to recruit sufficient numbers for a between subjects genetic analysis for this SNP (major allele vs minor 
allele-carriers) we will obtain a sufficient sample size for an exploratory polygenetic assessment of several possible 
genetic variants selected for functional relevance and minor allele frequency. Although the results of the polygenetic 
analysis will not provide the same specificity in determining the moderating contribution (effect size of each variant), 
it may provide an indication as to which genes/variants deserve more targeted investigation.  
Introduction                                                                                                  Page 40
Contact PD/PI: Jones, Jermaine D


SPECIFIC AIMS 
Overview: It is estimated that worldwide there are over 75 milliion abusers of amphetamines and cocaine.  
Despite the public health significance of psychostimulant abuse, there remains no FDA-approved medication to 
facilitate treatment. In addition to treating alcohol abuse, naltrexone (NTX) has shown some promise in treating 
stimulant abuse (for which there are no pharmacotherapies). The abuse liability of amphetamines (AMPH) and 
other psychostimulants is most commonly attributed to their enhancement of mesolimbic dopaminergic 
transmission (Di Chiara & Imperato 1988). Additionally however, there is evidence that stimulant drugs modulate 
the endogenous opioid system (Wang and McGinty, 1995; Fagergren et al, 2003). In addition to being a non-
specific opioid antagonist, NTX inhibits dopamine (DA) neurons within the ventral tegmental area and diminishes 
dopamine function within the nucleus accumbens and nearby basal brain regions (Brahen et al 1977; Herridge et 
al 1988; Martin et al 1973).  
Preclinical and clinical studies have provided data suggesting that NTX may be effective at reducing the 
(ab)use of AMPHs, however, a review of the literature reveals conflicting findings that require resolution. The 
introduction to genetic techniques to the study of drug abuse has helped to identify a number of genomic loci and 
variants that may moderate variability in treatment response. A recent meta-analysis concluded that the OPRM1 
A118G SNP (rs1799971) significantly moderates the treatment efficacy of NTX for alcohol abuse, increasing 
effectiveness by over 2 fold among G-allele carriers (AG/GG). The proposed application would be the first to 
investigate the utility of NTX for treating stimulant abuse, while taking into account the possible moderating effect 
of rs1799971 variation. More specifically, we propose investigating the interaction between oral NTX and 
intranasal (IN) methamphetamine (M-AMPH; 50mg/70kg), a commonly prescribed (Desoxyn) and abused 
amphetamine-type stimulant (Brant et al., 2014). By administering this dose of M-AMPH via a route with faster 
pharmacokinetics (intranasal), the proposed investigation will better model how amphetamine drugs are abused in 
the real world (Bolin et al., 2013; Choi et al., 2001; Karila et al., 2010; Hart et al., 2008). Therefore, this 
investigation will provide a more externally valid assessment of NTX’s treatment potential in comparison to 
previous studies. 
 
Potential participants who meet DSM-V criteria for stimulant use disorder will complete testing sessions 
where IN M-AMPH effects are assessed following pretreatment with NTX (0, 25, 50 mg). Naltrexone pretreatment 
effects upon the abuse liability of M-AMPH will be assessed using self-report measurements of positive subjective 
effects and drug self-administration. Medication effects on these validated predictors of abuse potential will be 
compared between A118G A allele homozygotes (AA) and G-allele carriers (AG/GG) in order to evaluate genetic 
moderation of treatment outcome.  In an exploratory endeavor, data from all participants (N =72) will be used to 
concurrently assess the ability of 5 functionally relevant genetic variants to predict NTX’s treatment efficacy 
[ANKK1 (rs1800497); DβH (rs1611115); DRD2 (rs2283265); OPRM1 (rs6912029), SLC6A3 (rs28363170)]. 
 
This investigation will seek to address the following specific aims: 
 
Primary Aim: Compare the ability of NTX to alter the subjective and reinforcing effects of IN M-AMPH between 
groups of OPRM1 A118G SNP carriers (AA vs AG/GG). 
 
We hypothesize that G-allele carriers will report dose-dependent reductions in positive subjective and 
reinforcing effects following NTX pretreatment. In comparison, AA homozygous participants will report 
significantly less NTX effects on these measures.  
 
 
Exploratory Aim: Assess the association between various functionally relevant candidate genes and NTX 
treatment response.  
 
We predict that the presence or absence of one or more of the target genetic variants will be significantly 
associated with (and predict) change in the positive subjective and reinforcing effects of M-AMPH following 0 
mg NTX and 50 mg NTX pretreatment. 
 
Impact: The proposed investigation will be the first study assessing genetic modulation of naltrexone’s effects 
upon the abuse liability of a stimulant drug (methamphetamine). The exploratory study will concurrently 
assess the ability of several functionally relevant gene variants to predict pharmacological treatment efficacy.  
In addition to its contribution to the further development of the first pharmacotherapy for stimulant abuse, this 
study may identify gene x pharmacological interactions contributing to the personalization of stimulant abuse 
pharmacotherapy.  
Specific Aims                                                                                                 Page 41
Contact PD/PI: Jones, Jermaine D


SIGNIFICANCE 
 
The Challenge of Stimulant Abuse: Abuse of stimulants is a serious public health problem. Of the 
approximately 210 million illicit drug users worldwide, approximately 54.8 million abuse amphetamines (AMPH)  
and approximately 21 million abuse cocaine (COC; United Nations Office on Drugs and Crime, World Drug 
Report, 2014).  In the United States, cocaine use has declined but the use of amphetamine-type drugs is on the 
rise. The rate of AMPH use in the United States now exceeds the historic level reached by cocaine in the period 
2000-2006.  
 
A Potential Solution: The abuse liability of AMPH and other psychostiumlants is most commonly 
attributed to its enhancement of mesolimbic dopaminergic transmission (Di Chiara & Imperato 1988). Additionally 
however, there is evidence that stimulant drugs modulate the endogenous opioid system (Wang and McGinty, 
1995; Fagergren et al, 2003). One medication that has shown promise as a pharmacotherapy for stiumlant abuse 
is naltrexone (NTX).  In addition to being a non-specific opioid antagonist, NTX inhibits dopamine (DA) neurons 
within the ventral tegmental area and diminishes dopamine function within the nucleus accumbens and nearby 
basal brain regions (Brahen et al 1977; Herridge et al 1988; Martin et al 1973).  
 
Consistent with these data, opioid receptor antagonism by NTX has been shown to attentuate the 
behavioral and neurochemical effects of AMPH.  In rodent models, NTX significantly attenuated AMPH-induced: 
dopamine release (at a dosage of 5.0 mg/kg) and locomotor behavior (at 3 mg/kg), AMPH-potentiated brain 
stimulation reward (at 0.5 mg/kg) and amphetamine-induced reinstatement of drug seeking (at 0.1 and 0.3 mg/kg) 
(Schad et al.,1995, Häggkvist et al., 2010; Häggkvist et al., 2009; Todtenkopf et al., 2009). The modulatory effect 
of NTX on amphetamine-induced behaviors has also been observed in rhesus monkeys, where 0.01–1 mg/kg of 
the drug dose-dependently decreased amphetamine self-administration (Jimenez-Gomez et al., 2011).  
 
The data from preclinical models have been corroborated using various human laboratory studies.  Three 
clinical amphetamine challenge studies have shown reductions in the subjective effects of d-amphetamine (D-
APMH) following acute pretreatment with NTX (50 mg, orally) (Jayaram-Lindstrom et al., 2004; 2008a; Marks et 
al., 2014). Combined, these findings strongly suggest that NTX may be useful in treating amphetamine abuse, 
and has led to its being tested in clinical trials. Jayaram-Lindstrom and colleagues (2005) found encouraging 
results in an open-label trial of NTX (50 mg), reporting significantly lower amphetamine use during treatment 
compared to pre-treatment. In a later randomized, placebo-controlled trial, these investigators found that NTX (50 
mg) significantly increased mean numbers of negative urine samples and continuous abstinence more than 
placebo (Jayaram-Lindstrom et al., 2008b). However, Grant et al. (2010) failed to find a robust treatment 
response in NTX-treated participants (at dosages of 50-150 mg/day).   
 
The data have also been inconsistent in trials of sustained-release NTX formulations. Tiihonen et al. 
(2012) assessed the efficacy of a NTX implant in individuals with comorbid opioid and amphetamine dependence. 
Naltrexone outperformed the placebo implant on retention and the proportion of drug-free urine samples. In 
another trial among patients with problematic amphetamine use, abstinence rates were 2.27 times greater among 
patients with NTX plasma levels >2 ng/ml. In contrast to these findings, one of the largest clinical trials of 
extended-release NTX for amphetamine abuse showed a lack of a treatment effect of the active formulation vs. 
placebo (Rúnarsdóttir and Hansdóttir, Annual Meeting of the College on Problems of Drug Dependence, June, 
2013).  
 
Genetic Variation as a Moderator of Treatment Response: In addition to the role that methodological 
differences among studies (e.g., in medication dosage, subject population, treatment duration, sample size) may 
have played in these findings, genetic variation may also have contributed to the inconsistency in treatment 
response. In support of this possibility is the fact that the heritability (proportion of observable differences in a trait 
between individuals that is due to additive genetic effects) of substance abuse is among the highest of any 
psychiatric disorder 40–80% (Agrawal et al., 2012; Kendler et al., 2000; Tsuang et al., 1996; Tsuang et al., 2001; 
Uhl et al., 1999).  The burgeoning area known as pharmacogenetics examines the moderating effects of genes on 
drug response, most commonly in laboratory studies or clinical trials.  
 
One relevant finding from pharmacogenetic research involves a single nucleotide polymorphism (SNP) in 
exon 1 of the mu opioid receptor gene (OPRM1). An A to G substitution (A118G, rs1799971) alters the receptor’s 
amino acid sequence by substituting aspartic acid for asparagine (Asn40Asp40).  A recent meta-analysis of one 
of the most commonly studied medication (NTX) x genotype (A118G) interactions in the treatment of alcohol 
dependence revealed a robust modulatory effect of this genotype on treatment outcome. In their meta-analysis of 
NTX pharmacogenetic clinical trials, Chamorro et al. (2012) concluded that G-allele carriers (AG or GG) were ~2 
times less likely to relapse than A-allele homozygotes when treated with NTX. Human laboratory studies have 
generally been consistent with the findings from clinical trials. Alcohol challenge studies have shown G-allele 
carriers to be more sensitive to the stimulant and hedonic effects of alcohol (Ray et al., 2010; Ray and Hutchison, 
2004), and to show a greater blocking effect on these responses when treated with NTX (Bujarski et al., 2012; 
Research Strategy                                                                                             Page 42
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Dose Time 
Mon
Tue
Wed
Thu
Fri
Dose Time 
Mon
Tue
Wed
Thu
Fri
Admission
Washout
Testing
Testing
Testing
Testing
Testing
Testing
9:00 AM
NTX 0mg
NTX 0mg
9:00 AM
NTX 50mg
NTX 50mg
NTX 25mg
NTX 25mg
10:00 AM
Sample:       
50mg vs $18
Choice:       
50mg vs $18
10:00 AM
Sample:      
50mg vs $18
Choice:       
50mg vs $18
Sample:      
50mg vs $18
Choice:       
50mg vs $18
11:00 AM
11:00 AM
12:00 PM
12:00 PM
1:00 PM
1:00 PM
2:00 PM
2:00 PM
3:00 PM
3:00 PM
4:00 PM
4:00 PM
5:00 PM
5:00 PM
Table 1: Sample Study Design
Week 1
Week 2
Ray et al., 2012; Setiawan et al., 2011). In light of the data showing a significant modulatory role of the A118G 
SNP (rs1799971) on NTX’s effects on alcohol, the current application is to examine whether the SNP moderates 
NTX’s effects on amphetamines.   
INNOVATION 
The proposed study will be the first investigation of NTX as a treatment for stimulant abuse to incorporate genetic 
variability as factor in treatment response. The primary design feature will be a prospective evaluation of NTX’s 
ability to attenuate the reinforcing and positive subjective effects of intranasal (IN) methamphetamine (M-AMPH) 
in rs1799971 A-allele homozygotes (AA) and G-allele carriers (AG or GG).  In an exploratory regression analysis 
we will concurrently assess the simultaneous impact of several genetic variants with relevant functional 
significance, whose moderating effects on NTX have yet to be extensively investigated.  The relative moderating 
effects of these genetic variants may be small individually, and therefore not detectable when they are assessed 
alone.  We will use a novel, polygenic approach to identify their combined contribution, which may serve as the 
basis for more targeted genetic analysis. Additionally, using intranasal amphetamine dosing will allow us to 
assess NTX’s effects on a more clinically relevant route of administration, which has previously not been tested in 
the clinical laboratory. Finally, by using common, validated methods to assess, diagnose, and test study 
participants, this study will contribute resources for use by all investigators studying addiction genetics. This type 
of candidate-gene pharmacogenetic study has the potential to enhance clinical care of substance use disorders 
(SUDs) by identifying risk factors and providing clinically useful predictors of pharmacotherapeutic outcome. 
APPROACH 
Design Overview  
Primary Study: The proposed study will compare the ability of NTX to alter the abuse potential of IN M-AMPH in 
individuals differentiated on the basis of the OPRM1 A118G SNP. Participants will be stimulant abusers of 
(Caucasian or of European decent, not seeking treatment) and consistent with most research on this genetic 
variant (Arias et al. 2014; Hendershot et al., 2014; Kim et al., 2009; Schacht et al., 2013) comparison genotypes 
will be grouped into A homozygotes (AA) vs. variant G-allele carriers (combined AG and GG). We plan to enroll 
72 participants in the proposed study. Based on previous research we anticipate that 25% of the total sample will 
be G-allele carriers (Chamorro et al., 2012; Chen et al., 2013; Orsziet al., 2009; Ray et al., 2009). A random 
subset of major allele carriers, equal in number to the final count of G-allele carriers (anticipated ~17) who 
complete the study, will be utilized as their comparator group. This will ensure equal N’s for the between-
genotypes comparisons.  
 
Participants who pass the extensive medical and psychological screening will be admitted to the inpatient 
unit of Columbia University Medical Center/ New York State Psychiatric Institute (NYSPI) for testing (see 
Recruitment). Following a 1-2 day washout, participants complete three lab sessions assessing the effects of 
pretreatment with 3 doses of NTX (0, 25 and 50 mg) in combination with IN M-AMPH (50mg/70 kg) in random 
order. The drug route/dose was chosen because our Division’s previous work has shown that it elicits robust self-
administration and positive subjective among stimulant-dependent populations (Comer et al., 1996; Hart et al., 
2001; 2002; 2008; Kirkpatrick et al., 2012) (further justification is provided in the Design Considerations section). 
Our extensive experience testing this drug/dose in our clinical drug self-administration procedures also provides 
us with a validated, comparable alternative monetary reinforcer to test it against (U.S. $18). See Jones et al., 
2013 for a review of the relevance and utility of laboratory models of drug administration. Naltrexone pretreatment 
is administered at 900hrs, followed by the IN administration of the sample M-AMPH dose (50mg/70kg) and $18 
(1000hrs, “Sample” session). The Sample session is followed by comprehensive quantification of the subjective, 
cognitive and physiological M-AMPH effects (see Assessments). On the following day, participants return to the 
lab to complete a self-administration or “Choice” session where they are asked to choose between 1/6th of the 
drug dose or dollar amount they sampled the day before (i.e., ~8 mg or $3). Sample and Choice sessions are 
Research Strategy                                                                                             Page 43
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completed on successive days (vs. the same day) in order to prevent carry over effects that we have previously 
observed with amphetamine self-administration (Comer et al., 1996; 2001). In the 6-trial, progressive ratio, choice 
procedure, after a choice is made between two options by clicking on its visual representation on the computer 
screen, the participant must complete the operant task requirement (finger presses on a computer mouse). The 
operant response requirement for each of the two options increases independently. The initial ratio requirement 
for each option will be 100 responses, which then increases progressively each time the option is selected (100, 
200, 400, 800, 1200, 1600). At the end of the self-administration task (approximately 4 PM), the participant will 
receive whatever (s)he had chosen. Money is added to the study payment, and the IN M-AMPH is given to the 
participant by a physician. Within this context the abuse potential of the drug is quantified in terms of the amount 
of effort participants are willing to devote to receive the drug, and/or the 
choice of drug vs. the monetary alternative reinforcer (Catania, 1971; Brady 
and Lucas, 1984). The effects of NTX pretreatment on the positive subjective 
and reinforcing effects of D-AMPH will be compared between the two A118G 
genotypes (AA vs AG/GG).  These data are expected to reveal a genotype 
by drug interaction, fictionalized in Figure 1 to the right. 
  Exploratory Study: An exploratory analysis will utilize combined data 
from all participants. A multiple regression will be employed to identify the 
possible combined moderation influence of a number of genetic variants on 
measures of methamphetamine’s abuse potential (drug self-administration) 
and NTX’s treatment efficacy (reduction in drug self-administration). Accordingly, a number of pharmacogenetic 
studies have found only combined effects of two or more variants (Chen et al., 2014; Dahl et al., 2006; David et 
al., 2007; Johnson et al., 2013; Johnstone et al., 2004; Quaak et al., 2012; Ray et al., 2014; Swan et al., 2007; 
Uhart et al., 2013). In this analysis, we have selected 5 target gene variants to use as predictor variables in a 
multivariate model to predict NTX’s effects on the changes in the M-AMPH abuse liability measures discussed 
above (i.e., the change in score between 0mg and 50mg NTX testing sessions). This analysis will explore the 
relative contribution of each of the individual genetic variants along with their combined effect (see Figure 2 
below).  The candidate genotypes were chosen based upon prior evidence of an association with amphetamine 
abuse, demonstrated functional relevance to the effects of psychostimulants and a minor allele frequency of 
greater than 15%: 
 
Ankyrin repeat and kinase domain containing 1 gene, ANKK1 
(rs1800497):  Adjacent to DRD2, associated with dependence 
on amphetamines and cocaine (Noble et al., 1993; Persico et 
al., 1996) and pharmacotherapy treatment outcome (Spellicy et 
al. (2013), 
 
Dopamine Beta Hydroxylase gene,  DβH (rs1611115):  
Accounts for up to 52% of the variation in DβH enzyme levels, 
shown to moderate cocaine pharmacotherapy treatment 
outcome (Deinum et al., 2004; Khonke et al., 2002; Kosten et 
al., 2013), 
 
D2 DA Receptor gene, DRD2 (rs2283265): Shown to interact 
with psychostimulant pharmacological treatment response 
(Spellicy  et al, 2013), 
 
Dopamine transporter (DAT) gene, SLC6A3 (rs28363170): 
Associated with altered DAT expression and DA clearance 
(Fuke et al., 2001), 
 
Mu opioid receptor gene, OPRM1 (rs6912029): Shown to 
moderate NTX treatment response (Al-Eitan et al., 2012). 
Recruitment and Screening: Recruitment for this study will occur primarily through advertisements in local 
newspapers. Potential applicants will first complete a telephone interview via which we will obtain information on 
demographics (name, telephone number, race, age, sex), medical, psychological, personal history, and details on 
their use of various prescription and illicit drugs. Participants who meet study criteria based on the telephone 
interview will be scheduled to come to NYSPI for additional screening procedures. After signing the screening 
consent form, participants will be evaluated by a team of research psychologists, nurses, and physicians. 
Screening procedures will include self-report and clinically-administered inventories. In total, screening 
procedures typically require 3-4 visits to complete.  
Screening assessments include: 
Research Strategy                                                                                             Page 44
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 
Beck Depression Inventory (BDI-II; Beck et al., 1972). The BDI-II is a 21-item self-report instrument that 
measures the severity of depression.  Each item is rated on a 4-point scale ranging from 0 to 3.  
 
State-Trait Anxiety Inventory (STAI; Spielberger, 1983).  The STAI is a self-report questionnaire consisting of 
two self-rated subscales, 20 items each, that rate trait anxiety and state anxiety.  Both the Trait and State 
subscales will be completed at screening.   
 
Structured Clinical Interview for DSM-IV or DSM-V expected to be available in 2015 (SCID; First et al., 1995). 
A semi-structured clinician administered interview used to derive major DSM-IV Axis I psychiatric diagnoses.  
 
Substance Use Inventory (Comer et al., 2008). This locally-developed self-report questionnaire will be used to 
determine quantity (i.e., dollars spent per day) and frequency (i.e., days) of substance use including: opioids, 
cocaine, alcohol, marijuana, amphetamines, sedatives, and phencyclidine. 
Other screening assessments include: medical history evaluation, physical examination, ECG, laboratory testing 
(including hematology, clinical chemistry, and thyroid panel), breathalyzer, urinalysis, urine pregnancy testing and 
11-panel urine drug toxicology. After reviewing screening results, a research psychiatrist will make the final 
decision as to whether the participant is eligible for the study. For those who agree to participate, informed 
consent for the study will be obtained and a training session, which is designed to familiarize participants with the 
study procedures, will be scheduled. 
All participants must meet all of the following inclusion criteria to be enrolled into the study: 
 
Male or female age 21 to 50 years. 
 
Meet DSM-5 criteria for moderate-severe stimulant use disorder (endorse 4 or more of the criteria listed in the 
DSM-5). In the past 12 months, used any of the commonly abused stimulants recreationally including 
methamphetamine, cocaine, or Ecstasy at least twice in one week; participants will be exposed to the same or 
less stimulant administration than they normally would outside of the laboratory.  
 
In otherwise good health based on complete medical history, physical examination, vital signs measurement, 
ECG, and laboratory tests (hematology, blood chemistry, and urinalysis) within normal ranges. 
 
Able to give written informed consent to participate. 
Participants will not be enrolled in the study if they meet any of the following exclusion criteria: 
 
Currently seeking treatment for a substance use disorder. 
 
DSM-V criteria for moderate-to-severe substance use disorders (except those involving cocaine, 
amphetamines and nicotine). 
 
Active psychiatric disorder that might interfere with participation or make participation hazardous.  
 
Lack of effective birth control; currently pregnant or breastfeeding. 
 
Uncontrolled neurological, cardiovascular, renal, and hepatic diseases, active tuberculosis, or any other 
disorder that might make administration of study medications hazardous. 
 
Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study 
drug, or require medication or medical treatment. 
 
Current treatment with a psychotropic medication. 
 
History of allergy, adverse reaction, or sensitivity to amphetamine.  
 
Pseudocholinesterase deficiency. 
 
Genotyping: After being consented at their initial visit to NYSPI, ~30 cc of venous blood will be collected in 8.5 ml 
ACD vacutainer tubes. Within 24 hr of their collection, blood samples will be transferred to Columbia’s Human 
Genetics Research Core where DNA will be isolated and stored at -20° C. Extracted DNA will be batched and 
sequenced by Columbia’s Taub Institute using PCR-based methods. Whole blood samples from each participant 
will also be sent to the NIDA Center for Genetic Study (NCGS) repository for the creation of cell lines, DNA, 
plasma or RNA for use among the broader scientific community. In addition to blood samples, we will also provide 
the NCGS with de-identified clinical data collected as a part of this investigation including: sex, race/ethnicity, age, 
SCID or psychiatric evaluation results.  
Laboratory Session Tasks and Measures:  
 
Reinforcing effects: M-AMPH breakpoint (the point at which operant responding ceases) and % of drug vs. 
money choices.  
 
Subjective Effects: Two questionnaires will be used to assess subjective drug effects. A 26-item visual analog 
scale (VAS) will be used to assess subjective and physiological drug effects such as “I feel a good effect” and 
“I feel high”. Participants rate each item on the scale from 'Not at all' (0 mm) to 'Extremely' (100 mm). In 
addition, a 6-item drug effects questionnaire (DEQ) will be used to measure drug effects (strength of drug 
effects, good effects, bad effects, willingness to take the drug again, drug liking, and similarity to other drugs). 
Participants select among a series of possible answers ranging from 0 ('No Effect’) to 4 ('Very Strong Effect’).  
Research Strategy                                                                                             Page 45
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 
Cognitive effects: The cognitive battery consists of two performance tasks: a 10-min divided attention task 
(DAT) and a 3-min digit-symbol substitution task (DSST, McLeod et al. 1982). The divided attention task 
consists of concurrent pursuit-tracking and vigilance components. Participants track a moving stimulus on the 
video screen using the mouse and signal when a small black square appears at any of the four corners of the 
video screen. The DSST consists of nine 3-row by 3-column squares (with one black square per row) 
displayed across the top of the computer screen. For each trial, a randomly generated number indicates which 
of the nine patterns should be emulated on a keypad by the participant. Participants will be required to 
emulate as many patterns as possible by entering the pattern associated with randomly generated numbers 
appearing on the bottom of the screen.  
 
Physiological Measures: For safety, oxygen saturation (%SpO2), respiration (breaths per minute), heart rate, 
and blood pressure (systolic and diastolic) will be measured every 5 minutes.  
 
Criteria for Terminating a Session & Criteria for Discontinuation/Dropout: See the Protection of Human 
Subjects section for medical criteria our Division has used extensively in order to ensure the safety of 
participants receiving intranasal psychostimulants.  
Discharge and Follow-up:  Participants will be paid $25/inpatient day, with a $25/day bonus for completing the 
study. At the conclusion of the study, participants will be given an exit interview during which the study will be 
described. Those who are interested in treatment for their drug use at the end of the study will be offered referrals 
to studies at our Substance Treatment and Research Service or other treatment providers. All participants will 
return to NYSPI weekly for payments, and at 1 and 3 months for follow-up visits. 
Design Considerations 
 
Drugs and Dosing: Methamphetamine was selected for the proposed study because it a commonly 
abused and prescribed (Desoxyn) amphetamine-type stimulant (Brant et al., 2014). There are also data to 
suggest that globally, ampetamines are being used as a substitute for cocaine, therefore data obtained here with 
M-AMPH may also be applicable to cocaine-abusing populations (United Nations Office on Drugs and Crime, 
2014).The dose of M-AMPH (50mg/70kg) selected for this study has also been shown to be highly rewarding in 
stimulant-abusing participants (Kirkpatrick et al., 2012). By administering this dose of M-AMPH via a route with 
faster pharmacokinetics (intranasal), the proposed investigation will better model how amphetamine drugs are 
abused in the real world (Bolin et al., 2013; Choi et al., 2001; Karila et al., 2010; Hart et al., 2008). Therefore, this 
investigation will provide a more externally valid assessment of NTX’s treatment potential in comparison to 
previous studies that have used an oral route of AMPH administration. Oral doses of 25 mg and 50 mg of NTX 
were chosen based on the existing literature.  Oral doses of 50 mg of NTX produce plasma levels sufficient to 
saturate mu opioid receptors for over 72 hr (Lee et al. 1988).  This finding, given the possibility of side effects, 
precludes the need to test higher doses (Anton et al. 2006; Garbutt 2010; Pfohl et al. 1986). The acute dosing of 
NTX replicates the dosing procedure of many of the NTX+AMPH challenge studies cited in the Significance 
section. Additionally, observations of robust reductions in amphetamine’s reinforcing and positive subjective 
effects by NTX, obtained in the laboratory setting are predictive of treatment response in clinical treatment 
settings (Haney et al., 2008; Jayaram-Lindstrom et al., 2004; 2008 a;b). 
 
Focus on A118G: In the current proposal, only one genetic variant was chosen for a priori, quasi-
experimental, between-groups testing, due to its substantiated moderating effect on the efficacy of the test drug 
(NTX). An alternative approach would be to test the effects of NTX on M-AMPH among a participant sample, then 
perform a posteriori comparisons of outcome between genotypes for many possible moderating variants. 
However, this approach would necessitate hundreds of participants to control for multiple testing well beyond the 
financial feasibility of any single clinical laboratory study. This statistical control is often ignored and is thought to 
lead to false positives and the failure to replicate among pharmacogenetic studies (Hart et al., 2013; Jones et al., 
2015 A, B; Munafo et al., 2007).  The exploratory aim of the proposed study attempts to simultaneously assess 
several possible genetic moderators (but whose influence is not as substantiated as the primary genetic target) 
using the combined study sample. Although this approach will not allow for specific determination of the effect 
size of each individual variant, positive results may serve as the basis for a more direct genotype comparison. 
Aims: 
 
Primary Aim: Compare the ability of NTX to alter the subjective and reinforcing effects of intranasal M-AMPH 
between groups of OPRM1 A118G SNP carriers (AA vs AG/GG). 
 
Exploratory aim: Assess the moderation of the subjective effects of M-AMPH by various functionally relevant 
candidate genes.  
Statistical Analyses 
 
Outcome Measures 
Research Strategy                                                                                             Page 46
Contact PD/PI: Jones, Jermaine D


Abuse Liability: The primary outcome measure of the reinforcing effects of the test drug (IN OXY) will be the drug 
break point assessed during the “choice” self-administration session (the point at which responding for the drug 
ceases).  In addition to this measure we will utilize peak (maximal drug effect throughout the session) observation 
of positive subjective drug effects (e.g., VAS assessed drug “Liking”) measured during the “sample” session 
(continuous variables). The distributions of all continuous variables will be checked for normality, and 
transformations will be employed, if necessary, before applying specific parametric techniques. Before performing 
specific analyses (described below), we will examine all outcomes for outliers. The distribution of demographic 
variables (e.g., gender, age) and measures of drug use will be examined and described in terms of means, 
standard deviations, proportions and 95% confidence intervals. 
Data Analysis Plan 
 
Primary Hypothesis and Testing:  SNP rs1799971 G-allele carriers will report dose-dependent reductions 
in positive subjective (i.e., “Liking” and reinforcing (i.e., lower breakpoint) following NTX pretreatment. In 
comparison, AA homozygous participants will report significantly less NTX effects on these measures. These data 
will be analyzed with a mixed-model analysis of variance (ANOVA) test comparing medication effects (PCB, NTX 
25, NTX 50) between the two genotype groups (AA vs AG/GG). If a significant interaction is found with this 
omnibus ANOVA, planned comparisons (t-tests) will be used to specify where significant differences exist. All 
tests for main effects (Genotype, NTX Dose) will be performed at two-tailed significance α=5%; all tests for 
interaction effects will be performed at significance level α=15%. Any comparison where homogeneity is violated 
will not be considered significant. Because we expect that the minor allele carriers will make up only 25% of the 
total sample (N=72), a random subset of the major allele carriers, equal in number to the final count of G-allele 
carriers (anticipated ~17) will be utilized as their comparator group. Although some between-groups statistical 
tests are robust against unequal sample sizes, differential sample size combined with the likely possibility of 
differential group variance, could easily double or triple the alpha error rate (Lipsey, 1990). Because sex has been 
shown to moderate the efficacy of NTX (Setiawan et al., 2011) participants will be stratified according sex to 
ensure comparable numbers of males and females in the AA and AG/GG groups.  
 
Exploratory Hypothesis and Testing: The presence or absence of one or more of the target genetic 
variants will be significantly associated with (and predict) change in the positive subjective and reinforcing effects 
of M-AMPH following 0 mg NTX and 50 mg NTX pretreatment. Multiple regression analysis will be used to identify 
which individual or combination of the 5 genetic variants best predicts those who respond to NTX (i.e., is there a 
genetic profile that may moderate the effect size of NTX’s treatment efficacy). A bivariate analysis will first be 
used to select eligible factors for the multivariate model (demographic variables will also be assessed in this 
model). To avoid situations where strong confounds could hide important predictors, a liberal p-value of <0.20 will 
used as a selection criterion for inclusion in the multivariate model. A stepwise backward selection procedure will 
then be used, based on a p <0.05 to identify the best multivariate model. Area under the curve (AUC) will be 
calculated to determine the robustness of the model. This statistical approach has provided significant data in 
other behavioral pharmacogenetic studies (Jones et al., Submitted). 
 
Genetic Analyses: For each polymorphism, a test for Hardy–Weinberg equilibrium will be performed to test 
for deviation from Hardy–Weinberg equilibrium by using the SNPstat software (Solé et al., 2006). For all the 
selected polymorphisms, we will consider both a log-additive, a dominant, or a recessive mode of inheritance. The 
Akaike information criterion (AIC) will be used to select the genetic model that best fits the data (i.e., the model 
with the lowest AIC score). 
Power Analysis: Power for the current study is based on previous investigations demonstrating a 
moderating effect of A118G on the effects of NTX. Effect size estimates concerning the impact of this SNP are 
derived from two alcohol pharmacogenetic challenge studies finding greater NTX attenuation of subjective ratings 
of “High,”  and “Euphoria” among G-allele carriers (Ray et al., 2012; Setiawan et al., 2011). Based on mean 
differences observed for NTX’s effects between AA and AG/GG groups in these two studies, a Cohen’s d effect 
size of 1.0 was estimated (assuming that each group varies 1.1 standard deviations from its mean). Given this 
effect size, a sample size of 17 per genotype would allow us ~90% power to detect a 20 mm difference in NTX’s 
effects on ratings of M-AMPH “Liking” between the AA and AG/GG groups. This power analysis is also applicable 
to the exploratory study. To achieve an N of 17 minor-allele carriers, we plan to test 72 participants in total.  This 
sample size would allow us to asses an effect size contribution from genetics variables as small as 0.12 (f2) in a 
regression model (R2).  When this effect size was imputed into G* Power 3.1.7 with the number of genetic 
variables under investigation in the exploratory analysis (5), a sample size of 72 participants should allow ~85% 
power to detect a significant model.  Because of the exploratory nature of this study, an α of 5% was used. 
Adjusting the alpha for all predictor variables to account for multiple testing would assume that the predictor 
variables are independent, which is not likely. However, once the data are collected, the investigators will be able 
to determine the relatedness of the predictor variables and adjust the alpha accordingly (i.e., Bonferroni adjusted 
α). Thus, with regard to both study aims, these calculations suggest that this study is suitably powered.  
Research Strategy                                                                                             Page 47
Contact PD/PI: Jones, Jermaine D


PROTECTION OF HUMAN SUBJECTS 
1. Risks to the Subjects 
Human Subjects Involvement and Characteristics 
Prospective research participants will be normal healthy men and non-pregnant women who will be 
evaluated according to the following inclusion/exclusion criteria: 
All participants must meet all of the following inclusion criteria to be enrolled into the study: 
 
Male or female age 21 to 50 years 
 
DSM-V criteria for moderate-to-severe stimulant use disorder  
 
In otherwise good health based on complete medical history, physical examination, vital signs 
measurement, ECG, and laboratory tests (hematology, blood chemistry, urinalysis) within normal 
ranges 
 
Able to give written informed consent to participate 
Participants will not be enrolled in the study if they meet any of the following exclusion criteria: 
 
Currently seeking treatment for a substance use disorder 
 
DSM-V criteria for moderate-to-severe substance use disorders (except those involving cocaine, 
amphetamines and nicotine) 
 
Active psychiatric disorder that might interfere with participation or make participation hazardous  
 
Lack of effective birth control; currently pregnant or breastfeeding. 
 
Uncontrolled neurological, cardiovascular, renal, and hepatic diseases, active tuberculosis, or any 
other disorder that might make administration of study medications hazardous 
 
Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion 
of study drug, or require medication or medical treatment 
 
Current treatment with a psychotropic medication 
 
History of allergy, adverse reaction, or sensitivity to amphetamines 
 
Pseudocholinesterase deficiency 
Sources of Research Material  
Screening evaluation and research forms completed by research staff and participants include: 
 
Blood sampling: (1) comprehensive metabolic panel collected during screening (2) identification of 
target genetic variants. 
 
Urine samples: to document drug and/or alcohol use, pregnancy testing, and urinalysis for general 
health.  
All data will be obtained specifically for research purposes and coded with a unique identifier assigned 
to each participant. Consent forms will contain participants’ names. 
Potential Risks 
Blood Drawing: During the screening assessments, two 30 cc venous blood samples will be collected, one 
for medical evaluation and another for genetic testing. Blood drawing may cause mild discomfort at the 
site where the needle is inserted, and it poses a small risk of bruising at the site as well as an extremely 
low risk of infection. 
Psychological Distress: The structured interviews, rating scales, and questionnaires should add no 
physical risk. However, because many of the interviews and assessments are time consuming to complete 
and involve topics of a sensitive nature, some people have found them to be physically or emotionally 
tiring. Patients are informed prior to study entry that they can refuse to answer any questions and that they 
Protection of Human Subjects                                                                                  Page 48
Contact PD/PI: Jones, Jermaine D


can request to stop at any time. If a participant becomes agitated during any of the interviews or 
assessments, he or she will be provided with therapeutic assistance. 
Amphetamine administration: Amphetamine-type stimulants (including methamphetamine) are used 
clinically for the treatment of ADHD and narcolepsy. Doses between 5 and 60 mg per day in divided doses 
are typically used for the treatment of narcolepsy. The major risks of intranasal M-AMPH administration 
are increased blood pressure and heart rate. Other side effects include excitation, restlessness, dizziness, 
insomnia, euphoria, dysphoria, tremor, headache, dry mouth, diarrhea, constipation, and weight loss. Less 
common side effects include seizures, blurred vision, increased thought disorders, psychosis, and 
hallucinations. Our Division has safely administered psychoactive stimulants including cocaine, 
amphetamine and methamphetamine via oral, smoked, intravenous and intranasal routes in numerous 
studies without significant medical complications (Comer et al., 1996, 2001, 2013; Collins et al., 2007; Hart 
et al., 2001, 2008; Foltin et al., 2004). Only prospective participants who use stimulants in a quantity 
greater than that we plan to administer in the proposed study will qualify for inclusion. 
Naltrexone Administration: Naltrexone may mildly impair the functioning of the liver. This effect on the liver 
will resolve after naltrexone is discontinued. Naltrexone may also cause stomach upset, nausea, and 
vomiting. In addition, administration of naltrexone may increase blood sugar levels, which may produce 
symptoms such as dizziness, increased breathing, dehydration, sedation, and localized seizures. Only two 
active NTX doses are administered as a part of the proposed investigation, therefore we anticipate a very 
small likelihood of these adverse effects. 
Subsequent Drug Use: The possibility of study participants increasing their drug use as a result of their 
participation in the proposed study is small. Previous studies have shown that administration of drugs of 
abuse to drug-abusing volunteers does not lead to increased drug use after study participation:  
 
Bigelow GE, Brooner RK, Walsh SL, Preston KL, Liebson IA. (1995) Community outcomes 
following research exposure to cocaine or opioids. In: IHL, editor. Problems of Drug Dependence 
1994: Proceedings of the 56th Annual Scientific Meeting. Washington DC: NIH; p. 354. 
 
Elman I, Krause S, Karlsgodt K, Schoenfeld DA, Gollub RL, Breiter HC, et al. (2001) Clinical 
outcomes following cocaine infusion in nontreatment-seeking individuals with cocaine  
dependence. Biol Psychiatry 49: 553–555. 
 
Fischman MW, Schuster CR, Resnekov L, Shick JF, Krasnegor NA, Fennell W (1976) 
Cardiovascular and subjective effects of intravenous cocaine administration in humans. Arch Gen 
Psychiatry 33: 983–989. 
 
Pratt WM, Davidson D. (2005) Does participation in an alcohol administration study increase risk 
for excessive drinking? Alcohol 37: 135–141. 
  
Analysis of our own 1 month follow-up data across 5 recently completed inpatient studies where drugs 
were administered found that participation decreases drug use and facilitates entry into treatment. More 
specifically, 42% of our study completers were not using heroin 1 month after study completion and 55% 
decreased their heroin use from 5.9 bags per day at baseline to 2.9 bags per day at the 1-month follow up 
visit. In addition, 21% initiated buprenorphine or methadone treatment, 6% enrolled in a detox program, 
and 25% were referred to treatment [Roux et al., (2012) Impact of inpatient research participation on 
subsequent drug use patterns: implications for ethics and public health. Addiction 107: 642-649].  A similar 
follow-up analysis of studies where cocaine was administered yielded similar results.  Cocaine use 
significantly decreased at 1 month (-$165.13/week) and 3 months (-$118.59/week) after study participation 
(p<0.001). This decrease was not accompanied by a change in other drug use, e.g., a compensatory 
increase in alcohol, marijuana or nicotine use [Kalapatapu RK et al., (2012) Substance use after 
participation in laboratory studies involving smoked cocaine self-administration. Drug Alcohol Depend 
120(1-3): 162-167]. These results are not surprising because those who volunteer for our studies generally 
have relatively long histories of drug use and are, by inclusion criteria, regular users who have no desire to 
cut down or stop their use. The amount of drug they receive is also less than what they would be 
administering outside of the laboratory. 
Protection of Human Subjects                                                                                  Page 49
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Inpatient Housing: The problems associated with living in the hospital have been minimal in the 
participants we have tested in other research studies. We describe the isolation, boredom and inactivity at 
length prior to signing the consent form. The risks involved in exposure to the laboratory are believed to be 
negligible. In numerous previous studies, participants have not found the experimental procedures or 
laboratory per se to be stressful or difficult. Of course, participants are free to leave the study at any time 
and care is taken to be sure that this is understood. During the last few days of the study and/or prior to 
discharge, participants will receive counseling about different treatment options. For those participants 
requesting outpatient treatment, appropriate arrangements will be made during the last week, including 
placement in an outpatient treatment study at our Substance Treatment and Research Service (STARS), if 
they are eligible, or participation in group therapy at STARS or Narcotics Anonymous. 
Pregnancy: Female participants must not be pregnant to be included in the study.  Urine pregnancy tests 
are performed at each screening visit and immediately prior to admission. 
Confidentiality:  Potential participants divulge information that is sensitive and may have adverse social 
consequences if released. This would include information released to insurance companies, health care 
agencies, or family members, or information made public in any way. A Certificate of Confidentiality will be 
obtained for the current study and procedures for protecting confidentiality of records will be followed.  
Specifically, all data records containing identifying information will be kept in locked files and on password-
protected computers.  Blood samples for genetic testing will be sent only with participant code numbers, 
with no potentially identifying information.  Only the study investigators will have access to the codes 
linking the participant to their identifying information. The contract agencies performing these genetic tests 
will not have access to the subjects’ identifying information. Only the primary investigator and other core 
study staff will have access to identifiable information, which will be maintained on site under lock and key. 
All computer data is stored without names or other uncoded identification. Patients will be identified only 
through a numerical code in all electronic databases.  
Genomic Information: Participants will be notified that these samples will be used for an investigation into the 
association between drug abuse and genotype, and that these samples will be archived for up to 15 years for 
future investigations. Participants will also be informed of the Genetic Information Nondiscrimination Act (GINA) 
that generally makes it illegal for health insurance companies, group health plans, and most employers to 
discriminate based upon genetic information. 
 
2. Adequacy of Protection Against Risks 
Screening: An extensive battery of screening tests, including psychometric evaluations, interview 
assessments, and a medical examination in order to provide as much information as possible upon which 
to base participant selection. 
The following procedures and exclusionary criteria are designed to minimize the risks to participants: 
 
Participants are excluded if they have severe psychiatric illness(es) (e.g. mood disorder with 
functional impairment or suicide risk, schizophrenia) that might interfere with their ability to 
participate in the study or their capacity to provide informed consent 
 
Current treatment with psychotropic medications is exclusionary due to possible adverse 
interactions with study medications 
 
Pregnancy is exclusionary due to the possible effects of the study medication on fetal development 
 
History of an allergic reaction to any medication administered as a part of this study 
 
The evaluating study psychiatrist physician reviews all medical assessments along with medical 
history to determine if any would make study procedures hazardous 
Participant Education 
All participants will be informed of the possible side effects and risks mentioned above, which will also be 
included in an informed consent document. For eligible participants, the study PI and research psychiatrist 
will describe the study in detail including study procedures, and possible risks and benefits of participation. 
Participants may sign the consent form only after reading it, having any questions answered, and being 
given a copy to keep. 
Protection of Human Subjects                                                                                  Page 50
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Consent Procedures 
Participants will provide informed consent to screening and all study procedures prior to testing. 
Participants are instructed to call us if any untoward effects occur after the laboratory session and are 
given an emergency contact number.  
Participant Monitoring and Removal from the Study 
The research team will continually assess the participant’s health throughout the inpatient period and will 
remove participants from the study if physical or mental deterioration is observed. The medical criteria 
below have previously been approved by NIDA to be used to terminate a laboratory session during which 
amphetamines were administered, and an individual’s participation in the entire trial.  
 
Criteria for Terminating a Session:  The occurrence of any of the following abnormalities in a 
participant’s vital signs will result in the immediate ending of a laboratory session: (a) Systolic blood 
pressure > 180 mm Hg, sustained for longer than 6 minutes (> 3 consecutive readings), (b) 
diastolic blood pressure > 120 mm Hg, sustained for longer than 6 minutes (> 3 consecutive 
readings), and (c) heart rate > (220 – subject age x 0.85) bpm, sustained for longer than 6 minutes 
(> 3 consecutive readings).  
 
Criteria for Discontinuation/Dropout: If two sessions are terminated due to abnormal vital signs, 
the participant will be discontinued from the research study and informed as to the reason that their 
participation is being ended and they will be counseled as described below for completers Upon 
removal of a participant from the study, he or she will be provided with the appropriate follow-up 
treatment by the study physician and research nurse.  
Confidentiality 
Information about participants will be kept confidential and managed according to the requirements of the 
Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Records are kept in locked files and 
released only with the participant’s consent. All data are stored without names or other coded 
identification. Participants will be identified only through a numerical code in databases, while a paper 
code list will be kept under lock and key by the principal investigator. Before any screening procedures are 
initiated, participants sign an IRB-approved HIPAA acknowledgement form. A Certificate of Confidentiality 
will also be obtained for this study. 
3. Potential Benefits of the Proposed Research to the Subjects and Others 
Although there are minimal direct benefits to the participants, we conclude that the scientific benefits of the 
proposed research outweigh the potential risks. 
4. Importance of the Knowledge to be Gained 
Currently little is known about how genetic factors modulate naltrexone’s effects on stimulant drugs. The 
proposed clinical investigation will be the first study assessing genetic modulation of naltrexone’s ability to 
alter the abuse liability of a commonly abused stimulant (M-AMPH). The study could identify an important 
Gene x Pharmacological interaction, contributing to the personalization of stimulant abuse 
pharmacotherapy. In addition we may also learn more concerning genetic risk factors for stimulant abuse.  
5. Data and Safety Monitoring Plan 
Adverse Event (AE) 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries are also regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• 
Results in study withdrawal 
• 
Is associated with a serious adverse event 
• 
Is associated with clinical signs or symptoms 
• 
Leads to additional treatment or to further diagnostic tests 
• 
Is considered by the study physician to be of clinical significance 
Protection of Human Subjects                                                                                  Page 51
Contact PD/PI: Jones, Jermaine D


 
Serious Adverse Event (SAE) 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• 
Fatal 
• 
Life-threatening 
• 
Requires or prolongs inpatient stay 
• 
Results in persistent or significant disability or incapacity 
• 
An important medical event 
All adverse events reported by the participant or observed by the research staff will be individually listed 
on our Adverse Event Form (AEF). The signs and symptoms, time of onset, duration, severity, medical 
intervention, follow-up procedures, and suspected relationship to study drug will be reported. Any AE 
(clinical signs and symptoms or laboratory test) associated with M-AMPH or naltrexone administration 
whether or not considered drug related, will be documented by the study physician or nurse.  Both the 
principal investigator and study physician provide ongoing review of the data and safety of the study 
participants during daily communication with the research staff, as well as at weekly lab meetings. In 
addition, ongoing and annual review of any serious adverse event is monitored by the IRB of the New 
York State Psychiatric Institute, NIDA, and the FDA.  The co-investigator, Dr. Comer, has served as a 
regular member of the IRB at the NYSPI since 2001, so she is intimately familiar with adverse and serious 
adverse events reporting requirements.  
 
Protection of Human Subjects                                                                                  Page 52
Contact PD/PI: Jones, Jermaine D


INCLUSION OF WOMEN AND MINORITIES 
 
Because the minor allele of the study’s primary target variant (A118G) is significantly less 
common among African-Americans (7%) than non-Hispanic Caucasians (28.7%) or Hispanics 
(27.8%)(Hastie et al., 2012), it will not be feasible to recruit an adequate number of participants 
of African ancestry to test the study’s primary hypothesis.  Further, it is not feasible to combine 
African-ancestry and European-ancestry participants in the same analysis because to do so 
would result in confounding due to population genetic differences.  Thus, we will enroll only 
participants who self-identify as White/Caucasian or as being of European ancestry.  Of this 
sample, we anticipate that approximately 30% will self-identify as Hispanic/Latino.  Based on 
previous experiences with recruiting stimulant abusers in the NYC area, we anticipate that 15% 
of our sample will be female (see Targeted/Planned Enrollment Table).  
 
 
Women & Minorities Inclusion                                                                                  Page 53
Contact PD/PI: Jones, Jermaine D


OMB Number: 0925-0002
Tracking Number: GRANT11962274
Funding Opportunity Number: PA-14-013. Received Date: 2015-07-15T14:35:23.000-04:00
Planned Enrollment Report
This report format should NOT be used for collecting data from study participants.
Study Title:
Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse
Domestic/Foreign:
Domestic
Comments:
Racial Categories
Ethnic Categories
 
Not Hispanic or Latino
Female
Male
Hispanic or Latino
Female
Male
Total
American Indian/Alaska Native
0
0
0
0
0
Asian
0
0
0
0
0
Native Hawaiian or Other Pacific Islander
0
0
0
0
0
Black or African American
0
0
0
0
0
White
14
30
7
19
70
More than One Race
0
0
0
0
0
Total
14
30
7
19
70
Study 1 of 1
                                                                                                              Page 54
Contact PD/PI: Jones, Jermaine D


INCLUSION OF CHILDREN 
Adolescents less than 21 years of age will be ineligible for participation in this study. 
More data on naltrexone’s safety and methamphetamine’s abuse potential in adolescents 
should be garnered before this procedure is attempted with younger participants. Additionally, 
adolescents < 21 who suffer from stimulant use disorder may require significantly different 
pharmacotherapeutic strategies than adults. 
 
Inclusion Of Children                                                                                         Page 55
Contact PD/PI: Jones, Jermaine D


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subjective response to amphetamine in healthy volunteers. J Clin Psychopharmacol 24: 665-
669. 
 
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for amphetamine dependence: compliance and tolerability. Nord J Psychiatry 59:167-171. 
 
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Jones J.D., Luba R.L., Vogelman J., & Comer S.D. Evidence of Genetic Modulation of Opioid 
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References Cited                                                                                              Page 62
Contact PD/PI: Jones, Jermaine D


 
June 27th, 2015 
 
Jermaine Jones, Ph.D. 
College of Physicians and Surgeons at Columbia University  
 
                               
Division of Substance Abuse 
 
 
 
       
1051 Riverside Drive 
New York, New York 10032 
 
 
 
Dr. Jones, 
 
 
I am glad to provide this letter to support the R21 application “Using Pharmacogenetics to Better 
Evaluate Naltrexone for Treating Stimulant Abuse.” I believe Dr. Jones has developed a very innovative way 
of evaluating the contribution of genetic involvement in efficacy of naltrexone to treat stimulant abuse. Over 
the past 25 years, I have been an active investigator in the genetics of substance abuse and have conduced: 
linkage, association, GWAS and candidate-gene studies.  
I have worked with Dr. Jones over the past 4 years a co-mention on his K01 grant “Genetic 
Contribution to the Abuse Liability of Oxycodone.” I have also previously worked with Columbia’s Division 
of Substance Abuse as an advisor on their P50 Center Grant (PI Herbert Kleber, MD). I have worked with 
Dr. Jones to refine the research plan of this proposal and believe the proposed study could have a significant 
impact on our understanding of genetic contribution to opioid use disorder. Dr. Jones is a very promising 
young investigator whose progression towards developing a pharmacogenetic research niche within his 
division I have helped foster over the past few years. I look forward to working with him on this exciting 
project. As I have discussed with Dr. Jones, I will be available to discuss and troubleshoot any issues that may 
arise during data collection, and assist with analysis for any interim analyses and the final study report.  I am 
excited to continue our cooperative research endeavors, and hope that this application is funded. 
 
Sincerely, 
 
 
 
 
 
Henry R. Kranzler, MD 
Professor of Psychiatry /Director  
Center for Studies of Addiction  
University of Pennsylvania 
Perelman School of Medicine  
Philadelphia VAMC 
Philadelphia, PA 19104 
Letters Of Support                                                                                            Page 63
Contact PD/PI: Jones, Jermaine D


Data and Resource Sharing  
 
 
NIH requires data sharing for all investigator-initiated grants with direct costs exceeding 
$500,000 in any single year.  This grant does not meet these criteria. However data from the 
studies in this R21 application will be shared in a number of ways. First, this protocol will be 
registered through the Protocol Registration System operated by the National Library of 
Medicine (NLM). The Protocol Registration System maintained by NLM will allow us to update 
information about the ongoing trial. The NLM publishes this information on their 
ClinicalTrials.Gov website. By providing details about this study, we also satisfy clinical trial 
registration requirements of the International Committee of Medical Journal Editors (ICMJE).  
 
Secondly, as a NIDA-funded human genetics study, this investigation will also be 
included among those participating in the NIDA Center for Genetic Studies (NCGS). 
Accordingly, the principal investigator (Dr. Jermaine Jones) will send the NCGS repository 
whole blood samples from each participant to possibly create cell lines, DNA, plasma or RNA. In 
addition to blood samples, the NCGS will also receive de-identified clinical and phenotypic data 
that will be collected as a part of this investigation including: subject ID, sex, ethnicity, age, 
DSM-V diagnosis, SCID or psychiatric evaluation results, along with Addiction Severity Index 
(ASI), Drug Abuse Screening Test (DAST-10) and Clinical Global Impression (CGI) scores. This 
data will be verified as needed, and regular updates will be provided throughout the grant award 
period. Blood samples, along with clinical and phenotypic data will be sent to the repository 
every 6 months and available for distribution 12 months after the termination of the grant period 
(including extensions). The PI will also apply for membership to the NIDA Genetics Consortium 
(NGC) and attend NGC meetings. A copy of the Informed Consent documents will also be 
provided to the NCGS/NGC to be searched or distributed to qualified investigators. Annual 
updates of all IRB-approved modifications to these documents will be sent to the NCGS.  
 
Lastly, data will also be shared via posters and talks at national and international 
conferences, such as the College on Problems of Drug Dependence (CPDD), Behavioral 
Pharmacology Society (BPS), the American College of Neuropsychopharmacology (ACNP), and 
International Behavioral Neuroscience Society (IBNS). Research manuscripts reporting the 
findings from the specific aims outlined in this study will be submitted for publication in peer-
reviewed journals. Taken together, we feel this constitutes an acceptable mechanism for 
sharing data. 
Resource Sharing Plans                                                                                        Page 64
Contact PD/PI: Jones, Jermaine D


v. 081911, p.  1
Name:
Date:________________
Interviewer:__________
How did you find out about our research?
How old are you?
Prescription Stimulant Use Information
Have you ever used prescription stimulants like (Adderral or Ritalin)?   Y          N
For medical purposes? Recreational purposes?  Both?  (Circle one)
Why did you 1st start using them?
How long have you used RxOs
What types have you tried before (name and dose of pills)?
How are/did you use them (route of admin table):
Life-
Very
Some-
Don't
Refuse to
time
Always
Often
Often
times
Never
know
answer
oral
chew
IN
IV
smoke
How many days per week do you use ?
How many pills do you use each day?
How many pills are prescribed each day?
How many pills do you use at a time?
Prescription Opioid Use Information
Have you ever used prescription opioids?   Y          N
For medical purposes? Recreational purposes?  Both?  (Circle one)
Why did you 1st start using them?
How long have you used RxOs
What prescription opioids are you using  currently (name and dose of pills)?
How are you using them (route of admin table):
Life-
Very
Some-
Don't
Refuse to
time
Always
Often
Often
times
Never
know
answer
oral
chew
IN
IV
smoke
How many days per week do you use ?
How many pills do you use each day?
How many pills are prescribed each day?
How many pills do you use at a time?
How long do you go between doses?
How long can you go without?
What happens (withdrawal symptoms)?
Have you ever used Methadone?   Y     N
RX?   Frm Street?     Both?
Do you currently use Methadone?  Y     N
RX?   Frm Street?     Both?
Have you ever used Suboxone?   Y      N
RX?   Frm Street?     Both?
Do you currently use Suboxone?  Y     N
RX?   Frm Street?     Both?
Do you have Medicaid?  Y     N   
What other medications are you currently taking?
    Obtaining RxOs
Do you buy prescription drugs on the street?   
How much do you pay per pill (drug and dose?)
Do you sell your pills?
Do you go to more than one doctor to get RxOs? 
How many docs and what specialty?
Do you get them from friends or family? 
Please specify:
Do you get them in any other ways?
 Which other ways?
Current
Current


v. 081911, p.  2
What side effects?
What do you like about RxOs?
Heroin Use Information
Have you ever used heroin?   Y          N
Have you ever used heroin for pain control?    Y           N
If yes, could you provide some details? What kind of pain? For how long? Was it effective?
Do you still use it for pain?   Y     N   notes:
     During the last 30 days
How may days per week do you use heroin?
How many bags a day do you use?
How much do you spend each day on H (avg & range)?
How many bags at a time do you use?
How long do you usually go between hits?
How long can you go without?
What happens (withdrawal symptoms)?
How long have you used H?
What do you like about H?
Do you usually do it alone?
with others?
Where do you usually buy it?
     Routes of H administration
LIFETIME
CURRENT USE
Very
Some
Don t
Refuse
Always
Often
Often
times
Never
know
to answer
IN
IV
IM
smoke
Other Drug Use Information
Do you currently drink alcohol?    Y     N 
LIFETIME
CURRENT USE
Very
Some-
Don't
Refuse
Always
Often
Often
times
Never
know
to answer
Beer:
Wine:
Hard liquor:
Monthly
2-4 
2-3
> 4
How often do you have a drink containing alcohol?
Never
or less
 x/mo
x/wk
x/wk
If > 4, how many days/wk exactly?________________
How many units of alcohol do you drink
 on a typical day when you are drinking?
1 to 2
3 to 4
5 to 6
7 to 8
10+
How often have you had 6 or more units if female, 
Daily or
or 8 or more if male,
almost
 on a single occasion in the last year?
Never
LT Mnthly Mnthly
Wkly
daily
During the last 30 days, did you use some following drugs ?
Route of administration (IN, SM, IV, PO, …)
How often do you use? (days/wk? days/mo?)
How much do you use per episode of use?
Route of administration (IN, SM, IV, PO, …)
How often do you use? (days/wk? days/mo?)
How much do you use per episode of use?
Do you smoke cigarettes? Number/day? Brand?
How do you feel about your drug use?
Always chasing it
Distressed
Have to avoid withdrawals
Seeking treatment
OK with it
If I gave you $100 dollars today to spend only on drugs, what would you buy?
Smile
Easy
Pause
Hard
Cocaine
MJ
Cocaine/ crack
Benzos
Other Club Drugs
Ecstasy
MethAMPH
Marijuana
Hallucinogens
Barbiturates


v. 081911, p.  3
Heroin
EtOH
Rx Opioids
RxAMPH  _______
Do you combine any drugs?
Cocaine + MJ
Why?_______
RxO + Benzos
Why?_______
EtOH + Cocaine
Why?_______
RxO + Alcohol
Why?_______
H + Cocaine
Why?_______
RxO + Cocaine
Why?_______
H + Benzos
Why?_______
RxO + Other
Which other?_______
Why do you combine drugs?
What's the longest you've gone without X in the past month?
Cocaine
MJ
Heroin
Etoh
Rx Opioids
RxAMPH ______
Education:
GED
HS
Grade school
College
Job:
Flexible:
Jail (# days or years):
Misdemeanor
Drug Possession
Juvenile Delinquent
Weapon
Skill in avoiding
Probation
Lucky never got caught
Parole
Do you have any kids?
Who will take care of them during the study?
Have you ever been tested for HCV infection?
Yes
No
Was the last test....
+
-
Have you ever been tested for HIV infection?
Yes
No
Was the last test...
+
-
Mood:
Depressed
Romantic problems
Anxious
OK
Appearance:
Neat
Sloppy
Clear
Dreamy
Arms:
OK
Too many track marks
Other comments/concerns:
Clinical Summary:


 
1 
 
MEDICAL HISTORY QUESTIONNAIRE 
 
 
DO YOU:  
 
CURRENT 
PAST 
NONE 
 
COMMENTS 
 
 
 
wear glasses or contact lenses 
 
 
 
 
wear a hearing aid 
 
 
 
 
have trouble sleeping 
 
 
 
 
have trouble eating 
 
 
 
 
cough up blood 
 
 
 
 
walk in your sleep 
 
 
 
 
have an history of tuberculosis 
 
 
 
 
have any history of asthma 
 
 
 
 
have any history of heart trouble 
 
 
 
 
 
 
 
IS THER ANY HISTORY IN YOUR FAMILY INVOLVING: 
 
CURRENT 
PAST 
NONE 
 
COMMENTS 
 
 
 
high blood pressure 
 
 
 
 
heart problems 
 
 
 
 
diabetes 
 
 
 
 
tuberculosis 
 
 
 
 
sickle cell anemia 
 
 
 
 
cancer 
 


 
2 
 
 
 
 
emotional problems  
 
 
HAVE YOU EVER HAD, OR DO YOU CURRENTLY HAVE: 
 
CURRENT 
PAST 
NONE 
 
COMMENTS 
 
 
 
scarlet or rheumatic fever 
 
 
 
 
swollen or painful joints 
 
 
 
 
frequent or severe headaches 
 
 
 
 
dizziness or fainting spells 
 
 
 
 
eye trouble 
 
 
 
 
ear, nose or throat trouble 
 
 
 
 
hearing loss 
 
 
 
 
severe tooth or gum trouble 
 
 
 
 
lung disease 
 
 
 
 
an allergic reaction to medication 
or drugs 
 
 
 
 
sinus problems 
 
 
 
 
hay fever 
 
 
 
 
diabetes 
 
 
 
 
head injury 
 
 
 
 
skin disease 
 
 
 
 
thyroid trouble 
 
 
 
 
shortness of breath 
 
 
 
 
pain or pressure in the chest 
 
 
 
 
chronic cough 
 
 
 
 
palpitation or pounding heart 
 
 
 
 
high blood pressure 
 


 
3 
 
 
 
 
cramps in your legs 
 
 
 
 
frequent indigestion 
 
 
 
 
stomach, liver or intestinal trouble 
 
 
 
 
gall bladder trouble or gallstones 
 
CURRENT 
PAST 
NONE 
 
COMMENTS 
 
 
 
jaundice or hepatitis 
 
 
 
 
adverse reaction to drug or 
medicine 
 
 
 
 
broken bones 
 
 
 
 
tumor, growth, cyst, cancer 
 
 
 
 
rupture, hernia 
 
 
 
 
hemorrhoids 
 
 
 
 
frequent or painful urination 
 
 
 
 
bedwetting since age 12 
 
 
 
 
kidney stone or blood in urine 
 
 
 
 
sugar in urine 
 
 
 
 
changes in urination pattern 
 
 
 
 
V.D.- syphilis, gonorrhea 
 
 
 
 
recent weight gain or weight loss 
 
 
 
 
arthritis, rheumatism, or bursitis 
 
 
 
 
bone, joint or other deformity 
 
 
 
 
lameness 
 
 
 
 
loss of finger or toe 
 
 
 
 
painful shoulder or elbow 
 
 
 
 
recurrent back pain 
 
 
 
 
“trick” or locked knee 
 
 
 
 
foot trouble 
 


 
4 
 
 
 
 
paralysis 
 
 
 
 
blood disease 
 
 
 
 
epilepsy, fits, convulsions 
 
 
 
 
motion sickness 
 
 
 
 
depression or excessive worry 
 
 
 
 
nervous trouble of any sort 
 
 
 
 
loss of memory, amnesia 
 
 
 
 
periods of unconsciousness 
 
 
 
 
seeing or hearing things that aren’t 
there 
 
 
 
 
suspicious or paranoid thoughts 
 
 
 
Have you had any diseases or medical conditions that you feel are related to your use of drugs? If so, when/ what                  
       
                                                                                                                                                                                           
Have you had an X-ray within the last 3 months? Yes        _        _ No         _        _ Date & Place         _        _         
        _        _        _        _        _        _        _        _        _        _        _               _        _        _        _        _         _         
 
Do you currently use prescribed medications? Yes         _        _ No         _        _Type & Reason         _              _         
        _        _        _        _        _        _        _        _        _        _        _                         _        _        _        _        _        _              
Do you have any allergies to medications? Yes         _        _ No         _        _ Specify         _        _           _        _         
        _        _        _        _        _        _        _        _        _        _        _                _        _        _        _        _        _         
Do you have any allergies to foods? Yes         _        _ No         _        _ Specify         _        _           _        _        _         
        _        _        _        _        _        _        _        _        _        _        _        _        _        _        _                _        _         
Have you ever been treated for mental illness? Yes         _        _ No         _        _ Specify         _        _               _         
        _        _        _        _        _        _        _        _        _                _        _        _        _        _        _        _        _                  
Are you pregnant or possibly pregnant? Yes         _        _ No         _        _ 


 
5 
 
Are you using birth control? Yes         _        _ No         _        _ Type         _        _        _        _        _        _        _                  
 
HOSPITALIZATIONS DURING THE PAST 3 YEARS: (most recent first) 
 
NAME OF FACILITY 
DATES INVOLVED 
REASON 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initials:_       _       _       _        
 
 
 
 
 
Date _       _       _       _       _        
 


 
 
Initials:                                 _ Marital Status:                                 Age:                       Sex:                        Date:                  _         
Occupation:                                                                   Education: _                                                                                    _     
  
Instructions:  This questionnaire consists of 21 groups of statements.  Please read each group of statements carefully, 
and then pick out the one statement in each group that best describes the way you have been feeling during the past 
two weeks, including today.  Circle the number beside the statement you have picked.  If several statements in the 
group seem to apply equally well, circle the highest number for the group.  Be sure that you do not choose more than 
one statement for any group, including Item 16 (Changes in Sleeping Pattern) or Item 18 (Changes in Appetite).  
 
 
1. Sadness 
 
0 I do not feel sad 
1 I feel sad much of the time 
2 I am sad all the time 
3 I am so sad or unhappy that I can’t stand it 
 
2. Pessimism 
 
0 I am no discouraged about my future 
1 I feel more discouraged about my future than I 
used to be 
2 I do not expect things to work our for me 
3 I feel my future is hopeless and will only get worse 
 
3. Past Failure 
 
0 I do not feel like a failure 
1 I have failed more than I should have 
2 As I look back, I see a lot of failures 
3 I feel I am a total failure as a person 
 
4. Loss of Pleasure 
 
0 I get as much pleasure as I ever did from the things 
I enjoy. 
1 I don’t enjoy things as much as I used to 
2 I get very little pleasure from the things I used to 
enjoy 
3 I can’t get any pleasure from the things I used to 
enjoy 
 
5. Guilty Feelings 
 
0 I don’t feel particularly guilty 
1 I feel guilty over many things I have done or 
should have done 
2 I feel quite guilty most of the time 
3 I feel guilty all of the time 
6. Punishment Feelings 
 
0 I don’t feel I am being punished 
1 I feel I may be punished 
2 I expect to be punished 
3 I feel I am being punished 
 
7. Self-Dislike 
 
0 I feel the same about myself as ever 
1 I have lost confidence in myself 
2 I am disappointed in myself 
3 I dislike myself 
 
8. Self-Criticalness 
 
0 I don’t criticize or blame myself more than usual. 
1 I am more critical of myself than I used to be 
2 I criticize myself for all of my faults 
3 I blame myself for everything bad that happens 
 
9. Suicidal Thoughts or Wishes 
 
0 I don’t have any thoughts of killing myself 
1 I have thought of killing myself but I would not 
carry them out 
2 I would like to kill myself 
3 I would kill myself if I had the chance 
 
10. Crying 
 
0 I don’t cry anymore than I used to 
1 I cry more than I used to 
2 I cry over every little thing 
3 I feel like crying, but I can’t 
 
11. Agitation 
 
0 I am no more restless or wound up than usual 
1 I feel more restless or wound up than usual 
2 I am so restless or agitated that it’s hard to stay still 
3 I am so restless or agitated that I have to keep 
moving or doing something 
 


 
 
 
 
 
 
 
 
 
      _                _ Subtotal Page1 
 
 
 
 
 
 
 
 
      _                _ Subtotal Page 2 
 
 
 
12. Loss of Interest 
 
0 I have not lost interest in other people or activities 
1 I am less interested in other people or things than 
before 
2 I have lost most of my interest in other people or 
things 
3 It’s hard to get interested in anything 
 
13. Indecisiveness 
 
0 I make decisions about as well as ever 
1 I find it more difficult to make decisions than 
usual 
2 I have much greater difficulty in making decisions 
than I used to 
3 I have trouble making any decisions 
 
14. Worthlessness 
 
0 I do not feel I am worthless 
1 I don’t consider myself as worthwhile and useful 
as I used to 
2 I feel more worthless as compared to other people 
3 I feel utterly worthless 
 
15. Loss of Energy 
 
0 I have as much energy as ever 
1 I have less energy than I used to have 
2 I don’t have enough energy to do very much 
3 I don’t have enough energy to do anything. 
 
16. Changes in Sleeping Pattern 
 
0 I have not experienced any change in my sleeping 
pattern 
 
        1a   I sleep somewhat more than usual 
        1b   I sleep somewhat less than usual 
 
        2a   I sleep a lot more than usual 
        2b   I sleep a lot less than usual 
   
        3a   I sleep mores of the day 
        3b   I wake up 1-2 hours early and can’t get back     
               to sleep 
 
17. Irritability 
 
0 I am no more irritable than usual 
1 I am more irritable than usual 
2 I am much more irritable than usual 
3 I am irritable all he time 
 
18.  Changes in Appetite 
 
0 I have not experienced any change in my appetite 
 
        1a   My appetite is somewhat less than usual 
        1b   My appetite is somewhat greater than usual 
 
        2a   My appetite is much less than before 
        2b   My appetite is much greater than usual 
   
        3a   I have no appetite at all 
        3b   I crave food all the time 
 
19. Concentration Difficulty 
 
0 I can concentrate as well as ever 
1 I can’t concentrate as well as usual 
2 It’s hard to keep my mind on anything for very 
long 
3 I find I can’t concentrate on anything 
 
 
20. Tiredness or Fatigue 
 
0 I am no more tired or fatigued than usual 
1 I get more tired or fatigued more easily than usual 
2 I am too tired or fatigued to do a lot of the things I 
used to do 
3 I am too tired or fatigued to do most of the things I 
used to do 
 
21.  Loss of interest in Sex 
 
0 I have not noticed any recent change in my 
interest in sex 
1 I am less interested in sex than I used to be 
2 I am much less interested in sex now 
3 I have lost interest in sex completely 


Table 1:Testing Schedule 
Sample Session Events (Day 1) 
-60 
(1000 hrs) 
Physiological monitoring [(Blood Pressure, HR: every 5 minutes; ECG: 
continuous)], Urine Drug/Pregnancy Test 
 
Oral Naltrexone Administration (0 mg or 50 mg) 
-30 
Baseline: Physiological, Subjective, and Performance Effects 
 0        Sample: Intranasal M-AMPH, 30 mg + $15 
15  
Subjective Effects 
30  
Subjective, and Performance Effects 
45 
Subjective Effects 
60  
Subjective and Performance Effects 
75 
Subjective Effects 
90 
Subjective and Performance Effects 
105 
Subjective Effects 
120 
 
Subjective and Performance Effects 
135 
Subjective Effects 
150 
Subjective and Performance Effects 
165 
Subjective Effects 
180 
(1400 hrs) 
Subjective and Performance Effects 
 
Sobriety Check and Discharge 
 


 
 
*24-Hour Interval* 
Choice Session Events (Day 2) 
-60 
(1000 hrs) Self-Administration Task begin 
 
0 
M-AMPH and/or Money Administration   
Physiological monitoring [(Blood Pressure, HR: every 5 minutes; ECG: 
continuous)] 
 
180 
(1400 hrs)  
 
Sobriety Check and Discharge 


Table 2: Overall Study Design 
Week 1 
Week 2 
M 
 
T 
 
W 
Th 
 
Sample 
(0 mg NTX) 
F 
 
Choice 
Sa-Su 
M 
T 
 
Sample 
(50 mg NTX) 
W 
 
Choice 
Th 
F 
Sa-Su 
 
 
 














DEPARTMENT OF HEALTH AND HUMAN SERVICES 
Food and Drug Administration
Silver Spring MD  20993
IND 127115
IND ACKNOWLEDGEMENT
Sandra Comer, PhD
1051 Riverside Drive
Unit 120
New York, NY 10032
Dear Dr. Comer:
We acknowledge receipt of your Investigational New Drug Application (IND) submitted under 
section 505(i) of the Federal Food, Drug, and Cosmetic Act (FDCA).  Please note the following 
identifying data:
IND NUMBER ASSIGNED:
127115
SPONSOR:
Sandra Comer, PhD
PRODUCT NAME(S):
methamphetamine
DATE OF SUBMISSION:
June 24, 2015
DATE OF RECEIPT:
July 1, 2015
You may not initiate studies in humans until 30 days after the date of receipt shown above unless 
we notify you sooner that you may proceed.  If, on or before July 31, 2015, we identify 
deficiencies in the IND that require correction before human studies begin or that require 
restriction of human studies, we will immediately notify you verbally or in writing that 
(1) clinical studies may not be initiated under this IND ("clinical hold") or (2) certain restrictions 
apply to clinical studies under this IND (“partial clinical hold”).  If we place your human studies 
on clinical hold, you will be notified in writing of the reasons and the information necessary to 
correct the deficiencies.  In the event of such notification, you must not initiate or you must 
restrict such studies until you have submitted information to correct the deficiencies, and we 
have subsequently notified you that the information you submitted is satisfactory.
It has not been our policy to object to a sponsor, upon receipt of this acknowledgement letter, 
either obtaining supplies of the investigational drug or shipping it to investigators listed in the 
IND.  However, if the drug is shipped to investigators, they should be reminded that studies may 
not begin under the IND until 30 days after the IND receipt date or later if the IND is placed on 
clinical hold.
Reference ID: 3788662


IND 127115
Page 2
FDAAA TITLE VIII RESPONSIBILITIES
You are also responsible for complying with the applicable provisions of sections 402(i) and (j) 
of the Public Health Service Act (PHS Act) [42 USC §§ 282 (i) and (j)], which was amended by 
Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Public 
Law No, 110-85, 121 Stat. 904).
Title VIII of FDAAA amended the PHS Act by adding new section 402(j) [42 USC § 282(j)], 
which expanded the current database known as ClinicalTrials.gov to include mandatory 
registration and reporting of results for applicable clinical trials of human drugs (including 
biological products) and devices.
In addition to the registration and reporting requirements described above, FDAAA requires that, 
at the time of submission of an application under section 505 of the FDCA, the application must 
be accompanied by a certification that all applicable requirements of 42 USC § 282(j) have been 
met.  Where available, the certification must include the appropriate National Clinical Trial 
(NCT) numbers [42 USC § 282(j)(5)(B)].
You did not include such certification when you submitted this application.  You may use Form 
FDA 3674, “Certification of Compliance, under 42 U.S.C. § 282(j)(5)(B), with Requirements of 
ClinicalTrials.gov Data Bank,” [42 U.S.C. § 282(j)] to comply with the certification requirement.  
The form may be found at http://www.fda.gov/opacom/morechoices/fdaforms/default.html.
In completing Form FDA 3674, you should review 42 USC § 282(j) to determine whether the 
requirements of FDAAA apply to any clinical trial(s) referenced in this application.  Please note 
that FDA published a guidance in January 2009, “Certifications To Accompany Drug, Biological 
Product, and Device Applications/Submissions: Compliance with Section 402(j) of The Public 
Health Service Act, Added By Title VIII of the Food and Drug Administration Amendments Act 
of 2007,” that describes the Agency’s current thinking regarding the types of applications and 
submissions that sponsors, industry, researchers, and investigators submit to the Agency and 
accompanying certifications.  Additional information regarding the certification form is available 
at: 
http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCA
ct/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/uc
m095442.htm.  Additional information regarding Title VIII of FDAAA is available at: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html.  Additional information for 
registering your clinical trials is available at the Protocol Registration System website 
http://prsinfo.clinicaltrials.gov/.
When submitting the certification for this application, do not include the certification with other 
submissions to the application. Submit the certification within 30 days of the date of this letter.  
In the cover letter of the certification submission clearly identify that it pertains to IND 127115
submitted on June 24, 2015, and that it contains the FDA Form 3674 that was to accompany that 
application.
If you have already submitted the certification for this application, please disregard the above.
Reference ID: 3788662


IND 127115
Page 3
ADDITIONAL IND RESPONSIBILITIES
As sponsor of this IND, you are responsible for compliance with the FDCA 
(21 U.S.C. §§ 301 et. seq.) as well as the implementing regulations [Title 21 of the Code of 
Federal Regulations (CFR)].  A searchable version of these regulations is available at
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm.  Your responsibilities 
include:

Reporting any unexpected fatal or life-threatening suspected adverse reactions to this 
Division no later than 7 calendar days after initial receipt of the information 
[21 CFR 312.32(c)(2)].  
If your IND is in eCTD format, submit 7-day reports electronically in eCTD format via the 
FDA Electronic Submissions Gateway (ESG). To obtain an ESG account, see information 
at the end of this letter.
If your IND is not in eCTD format:

you should submit 7-day reports by a rapid means of communication, preferably by 
facsimile or email. You should address each submission to the Regulatory Project Manager 
and/or to the Chief, Project Management Staff;

if you intend to submit 7-day reports by email, you should obtain a secure email account 
with FDA (see information at the end of this letter);

if you also send copies of these reports to your IND, the submission should have the 
same date as your facsimile or email submission and be clearly marked as “Duplicate.”  

Reporting any (1) serious, unexpected suspected adverse reactions, (2) findings from other 
clinical, animal, or in-vitro studies that suggest significant human risk, and (3) a clinically 
important increase in the rate of a serious suspected adverse reaction to this Division and to 
all investigators no later than 15 calendar days after determining that the information 
qualifies for reporting [21 CFR 312.32(c)(1)].  If your IND is in eCTD format, submit 15-
day reports to FDA electronically in eCTD format via the ESG.  If your IND is not in eCTD 
format, you may submit 15-day reports in paper format; and

Submitting annual progress reports within 60 days of the anniversary of the date that the 
IND became active (the date clinical studies were permitted to begin) [21 CFR 312.33].
IND REPORTING AND SUBMISSION PROCEDURES
CDER has developed a web page that provides information regarding IND application reporting 
and submission procedures, which also includes information regarding product development for 
clinical investigations and expanded access for clinical treatment.  The web page may be found 
at:  
Reference ID: 3788662


IND 127115
Page 4
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/
ApprovalApplications/InvestigationalNewDrugINDApplication/ucm343349.htm  
CHARGING FOR AN INVESTIGATIONAL DRUG
We remind you that, under 21 CFR 312.8(a)(3), you may not charge for this investigational drug 
without prior written authorization from FDA.
GOOD LABORATORY PRACTICE
All laboratory or animal studies intended to support the safety of this product should be 
conducted in compliance with the regulations for "Good Laboratory Practice for Nonclinical 
Laboratory Studies" (21 CFR 58).  If such studies have not been conducted in compliance with 
these regulations, provide a statement describing in detail all differences between the practices 
used and those required in the regulations.
ENVIRONMENTAL ASSESSMENT
Box 13, item 7 of form FDA 1571 requests that either an "environmental assessment," or a 
"claim for categorical exclusion" from the requirements for environmental assessment, be 
included in the IND.  If you did not include a response to this item with your application, please 
submit one.  Information on environmental assessments is available in the guidance 
“Environmental Assessment of Human Drugs and Biologics.”  This document is available at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/u
cm070561.pdf.
PATIENT-FOCUSED ENDPOINTS
An important component of patient-focused drug development is describing the patient’s 
perspective of treatment benefit in labeling based on data from patient-focused outcome 
measures [e.g., patient-reported outcome (PRO) measures]. Therefore, early in product 
development (i.e., phase 1 or 2), we encourage sponsors to consider incorporating well-defined 
and reliable patient-focused outcome measures as key efficacy endpoints in clinical trials, when 
appropriate, and to discuss those measures with the Agency in advance of confirmatory trials.  
For additional information, refer to FDA’s guidance for industry Patient-Reported Outcome 
Measures: Use in Medical Product Development to Support Claims, available at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM193282.pdf. 
ABUSE POTENTIAL ASSESSMENT
Drugs that affect the central nervous system, are chemically or pharmacologically similar to 
other drugs with known abuse potential, or produce psychoactive effects such as mood or 
cognitive changes (e.g., euphoria, hallucinations) need to be evaluated for their abuse potential 
and a proposal for scheduling will be required at the time of the NDA submission 
[21 CFR 314.50(d)(5)(vii)]. For information on the abuse potential evaluation and information 
required at the time of your NDA submission, see the draft guidance for industry “Guidance for 
Reference ID: 3788662


IND 127115
Page 5
Industry Assessment of Abuse Potential of Drugs,” available at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM198650.pdf.
SUBMISSION REQUIREMENTS
Cite the IND number listed above at the top of the first page of any communications concerning 
this application.  Each submission to this IND must be provided in triplicate (original plus two 
copies).  Please include three originals of all illustrations that do not reproduce well.  Send all 
submissions, electronic or paper, including those sent by overnight mail or courier, to the 
following address:
Food and Drug Administration
Center for Drug Evaluation and Research
Division of Anesthesia, Analgesia, and Addiction Products
5901-B Ammendale Road
Beltsville, MD 20705-1266
All regulatory documents submitted in paper should be three-hole punched on the left side of the 
page and bound.  The left margin should be at least three-fourths of an inch to assure text is not 
obscured in the fastened area.  Standard paper size (8-1/2 by 11 inches) should be used; however, 
it may occasionally be necessary to use individual pages larger than standard paper size.  
Non-standard, large pages should be folded and mounted to allow the page to be opened for 
review without disassembling the jacket and refolded without damage when the volume is 
shelved.  Shipping unbound documents may result in the loss of portions of the submission or an 
unnecessary delay in processing which could have an adverse impact on the review of the 
submission.  For additional information, see 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Drug
MasterFilesDMFs/ucm073080.htm.
Secure email between CDER and sponsors is useful for informal communications when 
confidential information may be included in the message (for example, trade secrets or patient 
information).  If you have not already established secure email with the FDA and would like to 
set it up, send an email request to SecureEmail@fda.hhs.gov.  Please note that secure email may 
not be used for formal regulatory submissions to applications (except for 7-day safety reports for 
INDs not in eCTD format).
The FDA Electronic Submissions Gateway (ESG) is the central transmission point for sending 
information electronically to the FDA and enables the secure submission of regulatory 
information for review.  If your IND is in eCTD format, you should obtain an ESG account.  For 
additional information, see  
http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/.
Reference ID: 3788662


IND 127115
Page 6
If you have any questions, call me, at (301) 796-4131.
Sincerely,
{See appended electronic signature page}
Christopher Hilfiger
Regulatory Health Project Manager
Division of Anesthesia, Analgesia, and
   Addiction Products
Office of Drug Evaluation II
Center for Drug Evaluation and Research
Reference ID: 3788662


---------------------------------------------------------------------------------------------------------
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
CHRISTOPHER M HILFIGER
07/07/2015
Reference ID: 3788662
























DEPARTMENT OF HEALTH AND HUMAN SERVICES 
Food and Drug Administration 
Silver Spring,  MD  20993
IND 133276
STUDY MAY PROCEED
Jermaine Jones, PhD
Columbia University College of Physicians and Surgeons
New York State Psychiatric Institute
l051 Riverside Drive, Unit 120
New York, NY 10032
Dear Dr. Jones:
Please refer to your Investigational New Drug Application (IND) submitted under section 505(i) 
of the Federal Food, Drug, and Cosmetic Act (FDCA) for Naltrexone Hydrochloride.
We have completed our safety review of your protocol, and have concluded that you may 
proceed with your proposed clinical investigation.
In addition, we have the following comment:
Based on the information you have provided via reference, we are able to allow your 
study to proceed with the understanding that you have committed to provide an updated 
Certificate of Analysis for the methamphetamine drug substance when it becomes 
available to you.  The Certificate should be submitted prior to starting the study.
ADDITIONAL IND RESPONSIBILITIES
As sponsor of this IND, you are responsible for compliance with the FDCA 
(21 U.S.C. §§ 301 et. seq.) as well as the implementing regulations [Title 21 of the Code of 
Federal Regulations (CFR)].  A searchable version of these regulations is available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm.  Your responsibilities 
include:

Reporting any unexpected fatal or life-threatening suspected adverse reactions to this 
Division no later than 7 calendar days after initial receipt of the information 
[21 CFR 312.32(c)(2)].  
If your IND is in eCTD format, submit 7-day reports electronically in eCTD format via the 
FDA Electronic Submissions Gateway (ESG).  To obtain an ESG account, see information 
at the end of this letter.  
If your IND is not in eCTD format:
Reference ID: 4034757


IND 133276
Page 2

you should submit 7-day reports by a rapid means of communication, preferably by 
facsimile or email.  You should address each submission to the Regulatory Project 
Manager and/or to the Chief, Project Management Staff;

if you intend to submit 7-day reports by email, you should obtain a secure email account 
with FDA (see information at the end of this letter); 

if you also send copies of these reports to your IND, the submission should have the 
same date as your facsimile or email submission and be clearly marked as “Duplicate.”  

Reporting any (1) serious, unexpected suspected adverse reactions, (2) findings from other 
clinical, animal, or in-vitro studies that suggest significant human risk, and (3) a clinically 
important increase in the rate of a serious suspected adverse reaction to this Division and to 
all investigators no later than 15 calendar days after determining that the information 
qualifies for reporting [21 CFR 312.32(c)(1)].  If your IND is in eCTD format, submit 15-
day reports to FDA electronically in eCTD format.  If your IND is not in eCTD format, you 
may submit 15-day reports in paper format; and

Submitting annual progress reports within 60 days of the anniversary of the date that the 
IND became active (the date clinical studies were permitted to begin) [21 CFR 312.33].  
PATIENT-FOCUSED ENDPOINTS
An important component of patient-focused drug development is describing the patient’s 
perspective of treatment benefit in labeling based on data from patient-focused outcome 
measures [e.g., patient-reported outcome (PRO) measures].  Therefore, early in product 
development (i.e, phase 1 or 2), we encourage sponsors to consider incorporating well-defined 
and reliable patient-focused outcome measures as key efficacy endpoints in clinical trials, when 
appropriate, and to discuss those measures with the Agency in advance of confirmatory trials.  
For additional information, refer to FDA’s guidance for industry Patient-Reported Outcome 
Measures: Use in Medical Product Development to Support Claims, available at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
CM193282.pdf. 
SUBMISSION REQUIREMENTS
Cite the IND number listed above at the top of the first page of any communications concerning 
this application.  Each submission to this IND must be provided in triplicate (original plus two 
copies).  Please include three originals of all illustrations that do not reproduce well.  Send all 
submissions, electronic or paper, including those sent by overnight mail or courier, to the 
following address:
Reference ID: 4034757


IND 133276
Page 3
Food and Drug Administration
Center for Drug Evaluation and Research
Division of Anesthesia, Analgesia, and Addiction Products
5901-B Ammendale Road
Beltsville, MD 20705-1266
All regulatory documents submitted in paper should be three-hole punched on the left side of the 
page and bound.  The left margin should be at least three-fourths of an inch to assure text is not 
obscured in the fastened area.  Standard paper size (8-1/2 by 11 inches) should be used; however, 
it may occasionally be necessary to use individual pages larger than standard paper size.  
Non-standard, large pages should be folded and mounted to allow the page to be opened for 
review without disassembling the jacket and refolded without damage when the volume is 
shelved.  Shipping unbound documents may result in the loss of portions of the submission or an 
unnecessary delay in processing which could have an adverse impact on the review of the 
submission.  For additional information, see 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/Drug
MasterFilesDMFs/ucm073080.htm.
Secure email is required for all email communications from FDA to sponsors when confidential 
information (e.g., trade secrets, manufacturing, or patient information) is included in the 
message.  To receive email communications from FDA that include confidential information 
(e.g., information requests, labeling revisions, courtesy copies of letters), sponsors must establish 
secure email.  To establish secure email with FDA, send an email request to 
SecureEmail@fda.hhs.gov.  Please note that secure email may not be used for formal regulatory 
submissions to applications (except for 7-day safety reports for INDs not in eCTD format).
The FDA Electronic Submissions Gateway (ESG) is the central transmission point for sending 
information electronically to the FDA and enables the secure submission of regulatory 
information for review.  If your IND is in eCTD format, you should obtain an ESG account.  For 
additional information, see  
http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/. 
If you have any questions, contact Mavis Y. Darkwah, PharmD, Regulatory Project Manager, at 
(240) 402-3158.
Sincerely,
{See appended electronic signature page}
Sharon Hertz, MD
Director
Division of Anesthesia, Analgesia,
    and Addiction Products
Office of Drug Evaluation II
Center for Drug Evaluation and Research
Reference ID: 4034757


---------------------------------------------------------------------------------------------------------
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic
signature.
---------------------------------------------------------------------------------------------------------
/s/
----------------------------------------------------
SHARON H HERTZ
12/29/2016
Reference ID: 4034757


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
1
 
Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse 
Screening Consent Summary Form 
 
 
Purpose of Study  
The goal of this research study is to collect information on the effects of amphetamine-type drugs, how 
they interact with the medication naltrexone, and how genetics may alter this interaction.  Genetics is the 
study of how genes control characteristics like your hair and eye color. Just as differences in our genetic 
code help explain why we all look different, these differences can also help to explain why some 
medications are effective for some people but not for others. 
 
You are being asked to screen for this study as a stimulant user. By participating, you will help 
researchers meet the goals of the study. This study is being funded by the National Institute on Drug 
Abuse. Dr. Jermaine Jones is the principal investigator and the person in charge of the study. All 
screening and study procedures will be conducted at the New York State Psychiatric Institute (NYSPI).  
 
Participation in this screening is voluntary. If you decide not to participate, or if you later decide to stop 
participating, you will not lose any benefits to which you are otherwise entitled. A decision not to 
participate or withdraw your participation will not affect your current or future treatment at the New York  
State Psychiatric Institute. This is not a treatment study. Information is being collected for research 
purposes. Referrals for treatment are available at any time. You do not have to participate in this study in 
order to get a referral to help stop taking drugs. If you are interested in treatment, an appropriate 
treatment referral will be arranged.  
 
 
Study Procedures  
You have been selected as a potential research volunteer. In order to participate in the study, you must  
first pass medical and psychiatric screening. This will include answering a general health questionnaire  
and other questionnaires relating to drug use; receiving an interview by a psychologist; and a physical 
examination. An electrocardiogram will be done to check the functioning of your heart. Blood samples 
are also collected to assess your general physical health, and urine samples are collected to test for 
drugs of abuse as well as pregnancy. If you are a woman, you will be given a pregnancy test. If you think 
you might be pregnant, please tell the investigator. You will be given another pregnancy test before each 
testing session, and if it is positive you will not be eligible to participate.  Additionally, this study has a 
genetic component that requires the collection of a blood sample to extract DNA (described in detail in 
the Study Consent form). The cells of your body contain a molecule called deoxyribonucleic acid, or DNA 
for short.  DNA is passed down from your parents and carries a code, in the form of genes, which 
determines your physical characteristics, such as the color of your hair and eyes. 
 
If you are still eligible after the screening, the study will be described to you in detail and you will be given 
a detailed Study Consent form outlining all aspects of the study.  
 
 
Risks  
During blood drawing, there is a risk of slight discomfort and/or bruising at the site where the needle is 
inserted. Approximately 2 tablespoons will be taken for health testing. If you qualify for the study, another 
2 tablespoons will be collected for genetic testing (4 total tablespoons). When someone donates blood, 
32 tablespoons are taken on one occasion.  
 
The structured interviews and questionnaires are time consuming to complete and involve topics of a 
sensitive nature.  
 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
2
As in any research study, it is possible that personal information about you could become known to other 
people. The investigators will take precautions to prevent this from happening. Your name will not appear 
on any questionnaires or tests that you complete during the study. Instead, all questionnaires and tests 
you complete will be coded with a study code number. The results from your individual genetic analyses 
will be kept confidential as described above.  
 
Benefits  
You are not expected to benefit directly from participation in this study. However, research studies such 
as this one may help scientists investigating risk factors for drug abuse, and in the development of 
treatment medications. 
 
Confidentiality  
We have applied for a Certificate of Confidentiality issued by the National Institutes on Drug Abuse 
(NIDA). With this Certificate, the researchers cannot be forced to release any research data in which you 
are identified, even under a court order or subpoena, without your written consent. The Certificate does 
not prevent the researchers from reporting suspected or known neglect or sexual or physical abuse of a 
child, or threatened violence to self or others. Such information will be reported to the appropriate 
authorities.  
 
You should understand that a Certificate of Confidentiality does not prevent you or a member of your 
family from voluntarily releasing information about yourself or your involvement in this research.  If an 
insurer, employer, or other person obtains your written consent to receive research information, then the 
researchers may not use the Certificate to withhold that information. 
 
Records will only be available to research staff and to Federal, State and Institutional regulatory 
personnel (who may review records as part of routine audits). Your name and other personal identifying 
information will be stored in an electronically secure database at New York Psychiatric Institute. 
Electronic information is also coded and is stored on computers that are password protected. Signed 
consent forms and other forms containing identifying information will be kept in a locked file, and all 
interviews, assessments, etc. will be coded with initials and numbers.  
 
Compensation  
As a result of participating in this screening you will receive $50 per screening visit, to a maximum of four 
visits. If you are enrolled in the study and complete all study procedures, you will earn between $650 and 
$800.   
 
In Case of Injury  
Federal regulations require that we inform participants about our institution's policy with regard to 
compensation and payment for treatment of research-related injuries. If you believe that you have 
sustained an injury as a result of participating in a research study, you may contact the Principal 
Investigator at (646) 774-6113 so that you can review the matter and identify the medical resources that 
may be available to you 
  
Questions  
The investigators will answer to the best of his ability any questions that you may have now or in the 
future about the research procedures. You may contact the Principal Investigator, Dr. Jermaine Jones, 
who can be reached at (646) 774-6113, if you have any questions. You will be given a copy of this 
consent form to take home with you. If you have any questions about your rights as a research 
participant, want to provide feedback, or have a complaint, you may call the NYSPI Institutional Review 
Board (IRB). An IRB is a committee that protects the rights of human subjects in research studies. You 
may call the IRB Main Office at (646) 774-7155 during regular office hours. 
 
 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
3
Documentation of Consent 
 
 
 
I voluntarily agree to participate in the research study described above.  
 
 
Name of Participant__________________________________  
 
 
Signature of Participant_______________________________ Date_______________  
 
 
 
 
 
Investigator, Physician, or Nurse 
 
Printed Name__________________________________  
 
 
Signature______________________________________Date________________  


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
1
 
Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse 
 
Consent Summary Form  
 
Below is a summary of the study in which you are being asked to participate.  This outline is meant to be 
a guide for you to use while considering the study and reading the consent form. It is not meant to 
replace the consent form you will need to sign if you decide to participate in the study.  The consent form 
contains much more detailed information about the study and the risks you will need to consider in 
making your decision. 
 
 
You are being asked to participate in a research study that is attempting to collect information on 
the effects of an amphetamine drug, if they can be blocked by another medication, and how your 
genetics plays a role. Genetics is the study of how genes control characteristics like your hair and 
eye color. Just as differences in our genetic code help explain why we all look different, these 
differences can also help to explain why some medications are effective for some people but not 
for others. 
 
 
You will complete 4 laboratory sessions. During 2 of these sessions an amphetamine drug will be 
administered intranasally, along with an oral dose of the medication naltrexone.  During the other 
2 sessions you will have the opportunity to work for the drug or money by making finger presses 
on a computer mouse.  
 
Each laboratory session is about 4 hours long. 
 
 
Like all research, your decision to participate is up to you; taking part is voluntary. 
 
Risks of Study Participation: 
 
 
If you decide to participate in this study, there are possible side effects and potential risks you 
should know about, and these are detailed in the consent form.  
 
 
The major risk of study participation is related to amphetamine administration. There have been 
reports of death and potentially a heart attack associated with amphetamine use. On rare 
occasions amphetamine use has been associated with chest pain, temporary hallucinations 
(seeing and hearing things that were not present), disorientation, seizures and muscle stiffness. 
You may also experience: excitation, restlessness, anxiety, headache, dry mouth, diarrhea, 
constipation, rapid pulse, loss of appetite, fluttering of the heart, irregular heart beats, and 
occasionally nausea, dizziness, sedation, or tremors. 
 
Benefits 
This study is not designed to benefit you directly. The genetic results will not be available to you or 
your doctors. However, research studies such as this one may help scientists investigating risk 
factors for drug abuse, and in the development of treatment medications. 
 
Compensation 
You will be compensated for your time and effort. As in all research, it is your choice to participate in 
this study and you do not have to participate if you do not want to. Also, you may stop participating at 
any time.  Please read the Consent Form carefully and ask the study physician any questions or 
concerns you might have. 
 
You can contact Dr. Jermaine Jones at (646) 774-6113 with any questions. 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
2
 Consent Form  
 
Study Purpose: The goal of this research study is to collect information on the effects of amphetamine 
type drugs and how they interact with the medication naltrexone. As a part of this study we will look at 
differences in people’s DNA in an attempt to try to understand differences in how people respond to 
drugs. The cells of your body contain a molecule called deoxyribonucleic acid, or DNA for short.  DNA is 
passed down from your parents and carries a code, in the form of genes, which determines your physical 
characteristics, such as the color of your hair and eyes; and risk for some diseases. Just as differences 
in our genetic code help explain why we all look different, these differences can also help to explain why 
some medications are effective for some people but not for others.   
 
You are being asked to participate because you have some history of use of amphetamine drugs or other 
stimulants. By participating, you will help researchers meet the goals of the study. This study is being 
funded by the National Institute on Drug Abuse. Dr. Jermaine Jones is the principal investigator and the 
person in charge of the study. Study procedures will be conducted at the New York State Psychiatric 
Institute (NYSPI).  
 
Details about this study are discussed below. It is important that you understand this information so that 
you can decide if you want to be in this research study. You will be given a copy of this consent form. 
You should ask the researchers, or staff members who may assist them, any questions you have about 
this study at any time. This consent form may contain words that you do not understand. Please ask the 
study doctor or the staff to explain any words or information that you do not understand. You may take 
home an unsigned copy of this consent form to think about or discuss with your family or friends before 
making your decision to participate in the study.  
 
The study will enroll up to 70 people at NYSPI.  
 
Voluntary: Participation in this research study is voluntary. If you decide not to participate, or if you later 
decide to stop participating, you will not lose any benefits to which you are otherwise entitled. A decision 
not to participate or to withdraw your participation will not affect your current or future treatment at the 
New York State Psychiatric Institute.   
 
 
Alternative Treatments/Alternatives to Participation: This is not a treatment study. Information is 
being collected for research purposes only. The alternative to participating would be not to participate. 
Referrals will be given to you at the end of the study if you are interested in treatment for your drug use. 
This genetic study is intended to learn about treating drug abuse and not about you.  We will not be 
providing you with any information about your DNA or your risk for developing inherited illnesses. 
 
 
Study Procedures: If you decide to participate you will undergo the following procedures: 
 
You will participate in a total 4 laboratory sessions. On the morning of each laboratory session a urine 
sample will be collected to test for recent drug use, and for pregnancy (in women). If either test is positive 
you will not be eligible to participate. Each laboratory session will take approximately 4 hours to 
complete. On Day 1 you will receive an intranasal amphetamine drug and an oral drug prior to it. The oral 
drug will be an FDA-approved opioid receptor blocker (naltrexone) or placebo (sham medication without 
any effects). Whether you get naltrexone or placebo will be randomly determined (like flipping a coin), 
and you will not be told which one you get that day. For the next 3 hours after these drugs are given, you 
will be asked to answer questions on the computer about how the drug makes you feel (such as “I feel 
high” or “I feel a good drug effect”) and the way you might behave in pretend situations involving sex. At 
the end of the session, you will complete a field sobriety test. If you are not too high or intoxicated, we 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
3
will call a car service or taxi to take you to your home address. If medical staff feels you are overly 
intoxicated, you will be asked to wait with us until we feel it’s safe for you to leave.   
 
On the following day (Day 2) you will return to NYSPI and have the opportunity to work for the intranasal 
drug by making finger presses on a computer mouse. Like at the end of Day 1, you will be asked to 
complete a field sobriety test before leaving NYSPI.  You will repeat these two sessions (Day 1 & 2) 
again at least 3 days apart. For safety, we will monitor your heart rate, blood pressure and electrical 
activity of the heart throughout both sessions.    
 
 
We will ask for you to return about thirty days after your last session to complete a brief follow-up visit.  
 
Genetic Information: As a part of this study DNA samples are collected using 2 tablespoons of your 
blood. The purpose of this part of the research study is to look at differences in people’s DNA in an 
attempt to try to understand differences in how people respond to drugs.  Whole blood samples can be 
used to make a cell line (cells from participants’ blood will be cultured and kept alive forever to further 
study their DNA). The purpose of establishing a cell line is to create a source of DNA for storage in a 
repository for future research. The research on DNA and drug abuse will continue for a long time, and so 
your DNA may be available to researchers indefinitely. However, you may indicate at the end of this form 
how your genetic sample is used (check one). For the current study, samples will only be kept for a 
maximum of 5 years. If you change your mind about having your DNA used in future related research, 
you can tell us to remove and destroy the samples any time during or after the study. However, if you 
consent to having your sample used to create cell lines, you will not be able to withdraw consent to its 
use, since identifying information will be removed. 
 
Study Risks 
 
Amphetamine Administration: Amphetamine drugs are considered to have a high potential for abuse and 
there have been reports of death and potentially a heart attack associated with their use. In addition, on 
rare occasions amphetamine use has been associated with chest pain, temporary hallucinations (seeing 
and hearing things that were not present), disorientation, seizures and muscle stiffness. You may also 
experience: excitation, restlessness, anxiety, headache, dry mouth, diarrhea, constipation, rapid pulse, 
loss of appetite, fluttering of the heart, irregular heart beats, and occasionally nausea, dizziness, 
sedation, or tremors. 
 
The risks of snorting methamphetamine have not been well characterized. In addition to likely nasal 
tissue irritation and bleeding, we cannot rule out the possibility of more significant adverse effects 
including loss of smell, lung damage, inflammation and infection.   
 
Naltrexone Administration: Naltrexone may mildly impair the functioning of the liver. This effect on the 
liver will improve after naltrexone is discontinued. Naltrexone may also cause stomach upset, nausea, 
and vomiting. In addition, administration of naltrexone may increase blood sugar levels, which may 
produce symptoms such as dizziness, increased breathing, dehydration, sedation, and seizures. If you 
regularly use opioid medications like oxycodone or heroin, naltrexone may cause you to experience 
withdrawal symptoms.  
 
Behavioral Tasks Risks: You may feel uncomfortable discussing sexual behaviors.  
 
Pregnancy Risks: If you are female in your childbearing years, you will be asked to take a pregnancy test 
to ensure that you are not pregnant. If you are pregnant or trying to become pregnant, there may be risks 
to you or your unborn child. If you are nursing an infant, there may be risks to the infant.  Females must 
be either post-menopausal, surgically sterilized, or use an acceptable method of contraception (double 
barrier method like a condom with a spermicidal lubricant) to participate in this study. 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
4
 
Risks to Privacy: As in any research study, it is possible that personal information about you could 
become known to other people. The investigators will take precautions to prevent this from happening. 
Your name will not appear on any questionnaires or test that you complete during the study. Instead, all 
questionnaires and tests you complete will be coded with a study code number.  
 
Unknown/Unforeseeable Risks: In addition to the risks listed above, there may be some unknown or 
infrequent and unforeseeable risks associated with the use of this study drug. If you experience any 
symptoms you believe to be related to the study drug you should call the study staff at 646-774-6243. 
 
 
Study Benefits: You are not expected to benefit directly from participation in this study.  
 
 
New Information:  You will be informed verbally and in writing of any new information, findings or 
changes to the way the research will be performed that might change your willingness to continue your 
participation in this study. 
 
 
Compensation: You will receive $125 for each of the four completed laboratory sessions and $50 for the 
follow-up visit. With the additional money you could earn during the laboratory sessions, you could make 
up to $610.  Failure to comply with the study could result in dismissal from the study. If you are dismissed 
from the study or decide to withdraw from the study, you will still receive the payment for the parts that 
you completed.   
 
We are required by law to report your earnings to the IRS.  Therefore, your Social Security Number and 
amount earned will be reported, and you will receive the appropriate IRS form at the end of the year in 
which you were paid.  Please note that payment for this study may affect your eligibility for Medicaid and 
other city and state support services.  No information about which study you participated in will be 
provided to the IRS.   
 
Confidentiality: All written information acquired in this study will be stored in locked files and will be kept 
confidential to the extent permitted by law. All computer-stored information will be "coded"—labeled only 
with a code and on password-protected computers. These code numbers will not use a name or any 
other identifying features. Your name and other personal identifying information will be stored in an 
electronically secure database at New York Psychiatric Institute that is accessible only to the members of 
the research team.  
 
We have applied for a Certificate of Confidentiality issued by the National Institute on Drug Abuse. With 
this certificate, the researchers cannot be forced to release any research information in which you are 
identified, even under a court order or subpoena, without your written consent. The Certificate does not 
prevent the researchers from reporting suspected or known neglect or sexual or physical abuse of a 
child, or threatened violence to self or others. Such information will be reported to the appropriate 
authorities. You should understand that a Certificate of Confidentiality does not prevent you or a member 
of your family from voluntarily releasing information about yourself or your involvement in this research. If 
an insurer, employer, or other person obtains your written consent to receive research information, then 
the researchers may not use the Certificate to withhold that information. Records will be available to 
research staff, and Federal, State, and Institutional regulatory personnel (who may review records as 
part of the routine audits). 
Your genetic information will be kept confidential and de-identified. All records containing links and 
identifying information will be kept in locked files and on password-protected computers. This information 
will only be available to NYSPI personnel key to this investigation.  Your blood sample will be labeled 
with a code that will be used throughout screening and testing. The sample will not have your name, or 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
5
address on it. The laboratories carrying out the DNA analysis (Columbia University, Human Genetics 
Resources Core, 630 W. 168th St. New York, NY 10032) and LGC Genomics (100 Cumming Center, 
Beverly, MA 01915) will never know your identity. If you also agree to have your DNA stored for future 
research, this number will be removed from your sample so there will be no way to know that it came 
from you, and it will not be possible to trace your identity.  
 
The Genetic Information Nondiscrimination Act (GINA) provides additional protections for you against 
discrimination based upon your private genetic information. This Federal law generally makes it illegal for 
health insurance companies, group health plans, and most employers to discriminate against you based 
on your genetic information.  GINA does not protect you against genetic discrimination by companies that 
sell life insurance, disability insurance, or long-term care insurance or by adoption agencies. GINA also 
does not protect you against discrimination based on an already diagnosed genetic condition or disease. 
If you would like to know more about it you can discuss this with the principal investigator of this study 
(Dr. Jones, 646 774-6113) or you can go to the following website http://www.genome.gov/10002328. 
 
 
In Case of Injury 
 
In case of injury, New York State Psychiatric Institute will provide short term emergency medical 
treatment, which has been determined to be necessary by New York State Psychiatric Institute's doctors, 
and which is within the capability of New York State Psychiatric Institute to provide.  In addition, we will 
provide assistance in arranging follow up care in such instances. 
 
New York State Psychiatric Institute and Research Foundation for Mental Hygiene do not provide 
compensation or payment for treatment of research related injuries.  However, you should be aware that 
you do not give up your legal right to seek such compensation through the court by participating in this 
research. 
 
Questions 
The investigators will answer to the best of his/her ability any questions that the participant may have 
now or in the future about the research procedures, or about the subject's response to the procedures.  
You may contact the Principal Investigator, Dr. Jermaine Jones who can be reached at (646) 774-6113, if 
you have any questions. You will be given a copy of this consent form to take home with you. You will be 
notified of any significant new findings that may relate to your willingness to continue to participate in this 
study.   
 
 If you have any questions about your rights as a research participant, want to provide feedback, or have 
a complaint, you may call the NYSPI Institutional Review Board (IRB). An IRB is a committee that 
protects the rights of human subjects in research studies. You may call the IRB Main Office at (646) 774-
7155 during regular office hours. 
 
 
Documentation of Consent 
 
Dr. Jones may □, may not □ use my genetic sample can be used for the current study. 
Dr. Jones may □, may not □ use my genetic sample for future related studies of drug abuse. 


IRB# 7347 
                                                              
Dr. Jermaine Jones 
 
Nov, 2016 
 
 
 
6
Dr. Jones may □, may not □ use my genetic sample to create cell lines from my DNA for 
storage at a national repository.   Once the trial ends, I will not be able to request the destruction 
of the sample because the link of my DNA sample to my identity will have been removed. 
 
 
 
I have read and understand the preceding information describing this medical research study.  The study 
doctor or the study staff has explained it to me in detail and all of my questions have been answered to 
my satisfaction.   
 
I understand that I will receive a signed copy of this consent form for my records.  I voluntarily agree to 
participate in the research study described above. 
 
 
Name of Participant__________________________________  
 
 
Signature of Participant_______________________________ Date_______________  
 
 
Statement of the Investigator (M.D.)  
 
I have examined the participant named above for the purpose of determining whether he/she is capable 
of understanding the purpose, nature, risks, benefits and alternatives (including non-participation) of the 
research, making decisions about participation, and understanding that the decision about participation 
in the research will involve no penalty or loss of benefits to which the patient is otherwise entitled, for Dr. 
Jermaine Jones’ research project “Using Pharmacogenetics to Better Evaluate Naltrexone for Treating 
Stimulant Abuse.” On the basis of this examination I have arrived at the conclusion that this participant 
has this capacity at this time. 
 
 
Printed Name__________________________________  
 
 
Signature______________________________________Date________________  


Form #PP2: HIPAA Authorization for Research 4.14.14 
New York State Psychiatric Institute (NYSPI) 
Authorization to Use or Disclose Health Information during a Research Study 
Protocol Number: 
Principal Investigator: 
Name of Study: 
Before researchers can use or share any identifiable health information (“Health Information”) about you as part of the 
above study (the “Research”), the New York State Psychiatric Institute (NYSPI) is required to obtain your authorization. You agree 
to allow the following individuals and entities to use and disclose Health Information about you as described below: 
•
New York State Psychiatric Institute (NYSPI), your doctors and other health care providers, if any, and
•
The Principal Investigator and his/her staff (together “Researchers”).   Researchers may include staff of NYSPI, the New York
State Office of Mental Health (OMH), Research Foundation for Mental Hygiene, Inc. (RFMH), and Columbia University (CU),
provided such staff is a part of the study, and
•
Providers of services for the Research at CU, NYSPI and/or RFMH, such as MRI or PET, or  Central Reference Laboratories 
(NKI), if indicated in the consent form.
1.
The Health Information that may be used and/or disclosed for this Research includes:
All information collected during the Research as told to you in the Informed Consent Form.   
Health Information in your clinical research record which includes the results of physical exams, medical and 
psychiatric history, laboratory or diagnostic tests, or Health Information relating to a particular condition that is related  to 
the Research. 
Additional information may include: 
2.
The Health Information listed above may be disclosed to:
Researchers and their staff at the following organizations involved with this Research: 
The Sponsor of the Research, 
and its agents and contractors (together, “Sponsor”); and  
Representatives of regulatory and government agencies, institutional review boards, representatives of the Researchers 
and their institutions to the level needed to carry out their responsibilities related to the conduct of the research.   
Private laboratories and other persons and organizations that analyze your health information in connection with 
this study 
Other (family members or significant others, study buddies, outside agencies etc.) Specify: 
3.
By giving permission to release your Health Information as described above, you understand that your Health
Information may be disclosed to individuals or entities which are not required to comply with the federal and state privacy laws
which govern the use and disclosure of personal Health Information by NYSPI.   This means that once your Health

National Institute on Drug Abuse

NYSPI/Columbia University College of Physicians and Surgeons



 Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse
Jermaine Jones, Ph.D.
7347


Form #PP2: HIPAA Authorization for Research 4.1.14 
Information has been disclosed to a third party which does not have to follow these laws (e.g., a drug company or the Sponsor 
of the Research), it may no longer be protected under the HIPAA or NYS Mental Hygiene Law requirements but is subject to the 
terms of the consent form and may be subject to other state or federal privacy laws or regulations.  
4.
Please note that:
•
You do not have to sign this Authorization form, but if you do not, you may not be able to participate in the study or
receive study related care.  You may change your mind at any time and for any reason. If you do so, you may no
longer be allowed to participate in the study.  If you withdraw this Authorization the research staff and the Sponsor, if this
is sponsored research, may still use or disclose Health Information containing identifying information they already have
collected about you as needed to maintain the reliability of the research.  Any request to withdraw this Authorization
must be made in writing to (enter name and contact information below):
•
While the Research is going on, you may not be allowed to review the Health Information in your clinical research
record that has been created or collected by NYSPI.   When this research has been completed you may be allowed to see
this information.  If it is needed for your care, your Health Information will be given to you or your Doctor.
5.
This Authorization does not have an end date.
6.
You will be given a copy of this form after you have signed it.
I agree to the use and disclosure of Health Information about me as described above: 
__________________________________________                _____________________ 
Signature of Participant/ Legal Representative    
Date 
______________________________________ 
Printed Name of Participant 
______________________________________ 
Relationship of Legal Representative to Participant (if applicable) 
We also ask you or your legal representative to initial the statements below: 
I have received a copy of the NYSPI/OMH Notice of Privacy Practices. 
Dr. Jermaine Jones
NY State Psychiatric Institute (Unit 120), New York, NY 10032
646-774-6113


I’m going to be asking you about problems or difficulties you may have had, and I’ll 
be making some notes as we go along. Do you have any questions before we begin?  
 
MDE 
 
1 In the last two months, has 
there been a period of time 
when you were feeling 
depressed or down most of the 
day nearly every day?  
  
IF YES: How long did it last? 
(As long as two weeks?) 
A two-week period in the past 
two months characterized by 
depressed mood most of the 
day, nearly every day, as 
indicated by either subjective 
report (e.g. feels sad or empty) 
or observation (e.g. appears 
tearful).  
 
 
 
NO 
 
 
YES 
MDE 2 What about losing interest or 
pleasure in things you usually 
enjoyed?  
IF YES: Was it nearly every 
day? How long did it last? (As 
long as two weeks?) 
A two-week period in the past 
two months characterized by 
markedly diminished interest or 
pleasure in all, or almost all, 
activities most of the day, 
nearly every day (as indicated 
either by subjective account or 
observation made by others) 
 
NO  
YES 
MDE  
Is the answer to either 1 or 2 
YES?  
 
NO 
 
 
YES – 
SCID 
 
ME 
 
1 Have you ever had a period of 
time when you were feeling so 
good, excited, or hyper that 
other people thought you were 
not your normal self or you 
were so hyper that you got into 
trouble?  
IF YES: (Was that more than 
just feeling good? Did anyone 
say you were manic?) 
How long did that last (as long 
as one week)?   
A distinct period of abnormally 
and persistently elevated, 
expansive, or irritable mood 
lasting at least one week (or any 
duration if hospitalization is 
necessary).  
 
NO 
 
 
YES 
ME 2 If NO: What about ever having 
a period of time when you were 
so irritable that you found 
yourself shouting at people or 
starting fights or arguments 
(Did you find yourself shouting 
at people you really didn’t 
know)?  
IF YES: How long did that last 
(as long as one week)?   
NO  
YES 
ME  
Is the answer to either 1 or 2 
YES? 
 
NO 
 
 
YES – 
SCID 


PD 
 
 
Have you ever had a panic attack, when you suddenly felt 
frightened or anxious or suddenly developed a lot of physical 
symptoms?  
 
 
 
 
NO 
 
 
YES – 
SCID 
 
 
OCD  
Have you ever been bothered by thoughts that didn’t make any 
sense and kept coming back to you even when you tried not to 
have them?  
 
 
 
 
NO 
 
 
YES – 
SCID 
 
OCD  
Was there ever anything that you had to do over and over 
again and couldn’t resist doing, like washing your hands again 
and again, counting up to a certain number, or checking 
something several times to make sure that you’d done it right?  
 
 
 
 
NO 
 
 
YES – 
SCID 
 
GAD  
In the last six months, have you been particularly nervous or 
anxious?  
 
 
 
 
NO 
 
 
YES – 
SCID 
 
ED  
Have you ever had a time when you weighed much less than 
other people thought you ought to weigh?  
 
 
 
 
NO 
 
 
YES – 
SCID 
 
VR  
Have you ever been arrested or convicted for assault or any 
violent offence? What about being involved in violence when you 
weren’t arrested or charged with it?  
 
 
 
 
 
NO 
 
 
YES – 
Follow-
up 
yourself 
 


PTSD 
 
1 
Sometimes things happen to people that are extremely 
upsetting – things like being in a life threatening situation 
like a major disaster, very serious accident or fire, being 
physically assaulted or raped, seeing another person killed or 
dead or badly hurt, or hearing about something horrible that 
has happened to someone you are close to. At any time in 
your life, have any of these kinds of things happened to you?  
 
 
NO 
 
 
YES 
PTSD 2A If YES: Sometimes these things keep coming back in 
nightmares, flashbacks, or thoughts that you can’t get rid of. 
Has that ever happened to you?  
 
NO 
 
 
 
YES 
PTSD 2B If NO: What about being very upset when you were in a 
situation that reminded you of one of these terrible things? 
 
NO  
YES 
PTSD  
Is the answer to 1 AND 2A and/or 2B YES? 
NO 
 
 
YES – 
SCID 
 
Now I’d like to ask you about unusual experiences that people sometimes have.  
 
SCHZ 
 
1 Has it ever seemed like people 
were talking about you or taking 
special notice of you?  
If YES: Where you convinced they 
were talking about you, or did you 
think it might have been your 
imagination? 
If YES or NO: What about 
receiving special messages from 
the TV, radio, or newspaper, or 
from the way things were arranged 
around you?  
 
Delusions of reference – i.e. 
events, objects, or other 
people in the individual’s 
immediate environment have 
a particular or unusual 
significant.  
NO 
 
YES 
SCHZ 2 What about someone going out of 
their way to give you a hard time, 
or trying to hurt you?  
 
 
 
Persecutory delusion, i.e. the 
individual (or his or her 
group) is being attacked, 
harassed, cheated, persecuted, 
or conspired against.  
NO 
 
YES 
SCHZ 3 Did you ever feel that you were 
especially important in some way, 
or that you had special powers to 
do things that other people 
couldn’t do?  
 
 
Grandiose delusion i.e., 
content involves exaggerated 
power, knowledge or 
importance, or a special 
relationship to a deity or 
famous person.  
 
 
 
NO 
 
YES 


SCHZ 4 Did you ever feel that something 
was very wrong with you 
physically even though your doctor 
said nothing was wrong…like you 
had cancer or some terrible 
disease?  
Have you ever been convinced that 
something was very wrong with 
the way that a part or parts of 
your body looked?  
 
Somatic delusion i.e. content 
involves change or 
disturbance in body 
appearance or functioning.  
NO 
 
YES 
SCHZ 5 Did you ever have any unusual 
religious experiences? 
 
Religious delusion 
NO 
 
YES 
SCHZ 6 Did you ever hear things that other 
people couldn’t hear, such as 
noises, or the voices of people 
whispering or talking? (Were you 
awake at the time?  
If YES: What did you hear? How 
often did you hear it?  
 
 
 
Auditory hallucinations 
NO 
 
YES 
SCHZ 7 Did you ever have visions or see 
things that other people couldn’t 
see? (Were you awake at the time?  
 
 
 
Visual hallucinations 
NO 
 
YES 
SCHZ 8 What about strange sensations in 
your body or on your skin?  
 
 
 
 
Tactile hallucinations 
NO 
 
YES 
SCHZ  
Is the answer to 1, 2, 3, 4, 5, 6, 7, or 
8 YES? 
 
NO 
END 
 
YES – 
SCID 
 
__________________________ was interviewed for participation in an opioid laboratory study. The 
candidate showed no indication of current depression or GAD, or lifetime panic disorder, OCD, PTSD, 
anorexia, mania or psychotic illness. The candidate denied a history of significant violence.  
Signed: _________________________________ Printed:_________________________________ 
Date:___________________________________