Effect of Pain Catastrophizing on Prescription Opioid Craving
Phase: NA
Conditions: Chronic Pain
Sponsor: Stanford University

 
Effect of Pain Catastrophizing on Prescription 
Opioid Craving 
NCT04097743 
February 14, 2024 
 
1. 
PURPOSE OF THE STUDY 
a. 
Brief Summary 
Adherence to prescription opioid and opioid tapering as indicated are critical for safe 
chronic opioid therapy for chronic pain, but this can be difficult for patients experiencing 
prescription opioid craving. 
 
Because pain catastrophizing is proposed as a possible treatment target by our and others’ 
preliminary results, the proposed study aims to determine whether pain catastrophizing is 
a treatment target to reduce prescription opioid craving and to investigate whether 
negative affect and stress hormones are potential mediators. 
b. 
Objectives 
We hope to learn whether a psychology intervention to lower pain catastrophizing will 
reduce opioid craving, and whether psychological and physical distress will be potential 
mediators of the treatment effect. 
c. 
Rationale for Research in Humans 
The purpose of this study is to examine the effect of a psychological  
intervention on opioid craving and medication misuse in patients taking prescription 
opioid for pain management. 
2. 
STUDY PROCEDURES 
a. 
Procedures 
Potentially eligible patients will complete an online prescreening survey. Based on the 
responses to the online prescreening survey, potentially eligible patients will be contacted 
via phone for additional explanation about the study to the patient, the brief phone 
screening to ensure the eligibility, and scheduling a laboratory experiment visit. As 
recommended not to ask a sensitive question (I.e., suicidal thought) during the phone 
screening, we will inform participants over the phone that their eligibility can be fully 
determined only after the full consent in the laboratory and we will pay their travel ($25 

02/14/2024 
 
Page 2 of 15 
for those living within an 1-hour driving distance and $50 for those living beyond it).  
 
Potentially eligible patients will be invited for a laboratory experiment (Study 1, 1.5 
hours). After obtaining a consent and determining the eligibility, participants will 
participate in the Study. We will utilize the suicide protocol if a participant is ineligible 
due to a suicidal ideation. Arm 1 study consists of two Studies; Study 1 will be a 
laboratory experiment and Study 2 will be a daily home practice. For Study 1, 
participants will be randomized to three conditions using previously validated protocols 
(Roditi et al., 2009, Taub et al., 2017): control, pain catastrophizing induction, and 
reduction. For Study 2, participants will be randomized again to two conditions: control 
and pain catastrophizing reduction.  
 
During the Study 1 laboratory experiment, patients will undergo 1) vital sign checks 
(heart rate, blood pressure, body temperature), 2) blood draw(7 ml) and salivary sample 
collection, 3) a pain catastrophizing protocol with a cold pressor testing, and 4) FOUR 
salivary sample collections (immediately after pain catastrophizing  
protocol, 10 min, 20 min, & 30 min after the cold pressor test). Patients' physiological 
states will be  
continuously monitored such as Heart Rate, Skin Conductance, skin temperature, 
Respiration Rate, facial EMG, and blood pressure.  
 
This study will use previously validated two pain catastrophizing protocols (Taub et al, 
2017 and Roditi et al, 2009). Briefly, the induction procedures are; first, ask participants 
to think and write about their past pain flare up episode for 10 minutes and then, read 10 
pain catastrophizing statements. Secondly, participants will read a pain catastrophizing 
statement of their choice out loud while putting their non-dominant hand in a cold water. 
The reduction procedures are; first, ask participants to think and write about their best 
pain management case for 10 minutes and then, read 10 pain coping statements. 
Secondly, participants will read a coping statement of their choice out loud while putting 
their non-dominant hand in a cold water.  
 
After completing Study 1, the participants will receive instruction about Study 2, which 
includes daily home practice of coping statement for 7 days (delivered via REDcap 
system), completing a daily survey for 14 days (5 minutes, delivered via REDcap 
system), and donate salivary cortisol (at the time of waking up, 30-min after waking up, 
and 9pm) at Day 1, 7, and 14. The collected salivary cortisol will be mailed to the lab 
with a pre-stamped envelope and an ice pack.  
 
If patients need to take certain medications (Steroid or Benzodiazepines) within 3 days of 
a saliva sample collection, saliva samples will not be collected.  
 
Added study 3 (arm 3)---------------------------------------  
Due to the unexpected event of COVID-19 pandemic, the study 3 (arm 3, online only) 
was added to examine the effect of pain catastrophizing on prescription opioid craving. 
Participants enrolled in the study 1 and 2 will NOT be allowed to participate in the study 
3. Different from study 1 and 2, participants in study 3 do not need to have a lab visit (all 
remote study tasks).  

02/14/2024 
 
Page 3 of 15 
 
Study 1, 2, and 3 will use the same inclusion criteria, but exclusion criteria for study 3 
will be different because study 3 will not do cold pressor testing on the non-dominant 
hand and will not collect blood and saliva samples. Therefore, we removed the following 
exclusion criteria in the study 1 and 2: needle phobia, skin condition on the non-dominant 
hand, daily use of cortisol or benzodiazepine. However, we added ineligibility criteria for 
inability to use heart rate monitoring device and app because Study 3 will collect resting 
heart rate daily. During the phone screening, we will ask all eligibility questions except 
one sensitive question (I.e., suicidal ideation). We will inform participants that we have 
one more eligibility question, which can be asked only after they sign the phone 
consenting.  
 
After the phone screening, we will do a phone consenting. A research coordinator will 
send the consent document to a participant via the REDCap system, which is a HIPPA 
compliant database. When sending the consent link, we will not include any PHI in the 
subject line. Then, the research coordinator will go over the consent over the phone and 
answer any questions. Participants will have a plenty of time to read the consent and can 
indicate whether they agree to participate or not on their own at home. Participants type 
their name and date if they agree to participate. After signing their consent, participants 
can download the consent and keep the copy for their own record. Once we obtain their 
consent, we will ask about suicidal ideation to determine their eligibility. Only the 
eligible participants will participate in Arm 3 study. We will use a suicide ideation 
protocol if a participate is ineligible due to suicide thought.  
 
Participant in the study 3 will do the baseline survey and be randomized into two 
conditions: daily coping statement practice (50%) and no coping statement (50%). The 
participants in the daily coping condition will be asked to choose the coping statement of 
the day and rehearse throughout the day for the 15 days. Except this difference, 
participants in the both conditions will do a daily survey and check the resting HR for 
five minutes for the 15 days. The participant will receive a wrist heart rate device (i.e., a 
heart rate measuring device) before the baseline survey and heart rate will be 
anonymously collected. Also, participants in the both conditions will do a cognitive 
testing at day 1 (baseline), day 8, and day 15 (final study). Different from the study 1 and 
2, study 3 will examine resting sympathetic cardiac levels and cognitive function as a 
mediator of the effect of the pain catastrophizing on craving.  
 
Stanford is the only study site, University of Oklahoma will only conduct EDTA sample 
analysis 
b. 
Procedure Risks 
All members of the study team have been trained to conduct the research procedures in 
the safest manner possible. There are no known risks to complete the study procedures as 
all the procedures and questionnaires are validated in this patient population and this 
medical setting. However, patients may feel temporarily uncomfortable for blood draw, 
laboratory pain testing, and completing some questionnaires. To minimize the risk, we 
will exclude patients with a needle phobia and history of vasovagal syncope for blood 
draw. Additionally, vital signs will be assessed prior to the blood draw and throughout 

02/14/2024 
 
Page 4 of 15 
the laboratory procedures. During the inform consent procedure, the patients will be 
informed that they can withdraw their consent anytime without penalty and their time 
will be compensated. Patient will have an option to not to answer any questions that make 
them feel uncomfortable. Finally, we will obtain the certificate of confidentiality to 
protect the privacy of research subjects by prohibiting disclosure of identifiable, sensitive 
research information to anyone not connected to the research except when the subject 
consents or in a few other specific situations. 
c. 
Use of Deception in the Study 
The exact study hypothesis and study procedures of part 1 are not completely described 
in the consent, but will be debriefed at the end of Experiment 1.Use of Audio and Video 
Recordings 
No audio or video recording will occur.Alternative Procedures or Courses of 
Treatment 
Participants are free to pursue the treatment of their choice at any time during and/or after 
the study. 
f. 
Will it be possible to continue the more (most) appropriate therapy for the 
participant(s) after the conclusion of the study? 
Participants are free to pursue the treatment of their choice at any time during and/or after 
the study 
g. 
Study Endpoint(s) 
Each participant will meet the study endpoint once he/she completes the daily survey for 
14 days after Study 1 laboratory visit. The study will end once the target enrollment is 
reached. 
3. 
BACKGROUND  
a. 
Past Experimental and/or Clinical Findings 
Chronic pain and opioid overdose are two critical public health problems in the US. 
About 25 million adults (11%) suffer from chronic daily pain and up to 8 million use 
opioids to manage chronic pain. Unfortunately, 46 people die daily from overdose of 
prescription opioids. For safe chronic opioid therapy for chronic pain, physicians monitor 
patients’ adherence to prescription opioids, and reduce or discontinue the prescription as 
indicated. Yet, adherence and cessation are not easy for some patients and one reason is 
opioid craving, a strong desire or urge to use opioids. Our preliminary data show about 
34% of patients on chronic opioid therapy report craving. Craving is strongly associated 
with opioid misuse and negative health outcomes. To date, we do not fully understand the 
underlying mechanisms of prescription opioid craving in chronic pain sufferers, and 
psychological treatment targets to reduce craving. Based on our pilot survey, patients 
endorsing craving reported greater pain catastrophizing than those endorsing no craving. 
Our other survey study also reported a positive link between pain catastrophizing and 
opioid craving in patients on chronic opioid therapy for chronic pain conditions. 
Although these findings propose a possibility that lowering pain catastrophizing may 
decrease opioid craving, cross-sectional observational studies are limited in investigating 
a causal association. Potentially, pain catastrophizing enhances stress-induced opioid 

02/14/2024 
 
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craving because stress-induced opioid craving is a well-established phenomenon in 
studies of addiction, and pain catastrophizing is associated with greater pain and 
emotional distress in patients with chronic pain. Therefore, the proposed project seeks to 
determine: a) the effect of pain catastrophizing on prescription opioid craving in patients 
on chronic opioid therapy for chronic pain and b) psychological (negative affect) and 
physiological (cortisol, norepinephrine) distress as potential mediating variables. 
Findings from Past Animal Experiments 
NA 
4. 
RADIOISOTOPES OR RADIATION MACHINES 
a. 
Standard of Care (SOC) Procedures 
b. 
Radioisotopes 
i. 
Radionuclide(s) and chemical form(s) 
NA 
ii. 
Total number of times the radioisotope and activity will be administered (mCi) and 
the route of administration for a typical study participant 
NA 
iii. 
If not FDA approved: dosimetry information and source documents (package insert, 
Medical Internal Radiation Dose [MIRD] calculation, and peer reviewed literature) 
NA 
c. 
Radiation Machines – Diagnostic Procedures 
i. 
Examination description (well-established procedures) 
NA 
ii. 
Total number of times each procedure will be performed (typical study participant) 
NA 
iii. 
Setup and techniques to support dose modeling 
NA 
iv. 
FDA status of the machine and information on dose modeling (if procedure is not 
well-established) 
NA 
d. 
Radiation Machines – Therapeutic Procedures 
i. 
Area treated, dose per fraction/number of fractions, performed as part of normal 
clinical management or due to research participation (well-established procedures) 
NA 

02/14/2024 
 
Page 6 of 15 
ii. 
FDA status of the machine, basis for dosimetry, area treated, dose per fraction and 
number of fractions (if procedure is not well-established) 
NA 
5. 
DEVICES USED IN THE STUDY 
a. 
Investigational Devices (Including Commercial Devices Used Off-Label) 
NA 
Investigational Device 1 
Name: 
NA 
Description: 
NA 
Significant Risk? (Y/N) 
NA 
Rationale for Non-Significant Risk 
NA 
 
b. 
IDE-Exempt Devices 
IND-Exempt Device 1 
Name: 
NA 
Description: 
NA  
 
6. 
DRUGS, BIOLOGICS, REAGENTS, OR CHEMICALS USED IN THE STUDY 
a. 
Investigational Drugs, Biologics, Reagents, or Chemicals 
Investigational Product 1 
Name: 
NA 
Dosage: 
NA 
Administration Route: 
NA 
b. 
Commercial Drugs, Biologics, Reagents, or Chemicals 
Commercial Product 1 
Name: 
NA 
Dosage: 
NA 
Administration Route 
N A 
New and different use? (Y/N) 
NA 
7. 
DISINFECTION PROCEDURES FOR MEDICAL EQUIPMENT USED ON BOTH HUMANS AND 
ANIMALS 
NA 
 
8. 
PARTICIPANT POPULATION 
a. 
Planned Enrollment 
(i) 156 participants (50% female) will be recruited at the Stanford Systems Neuroscience 
and Pain Lab. 
(ii) All participants will be enrolled at Stanford. Patients with chronic pain and opioid 
medication use will be enrolled. 

02/14/2024 
 
Page 7 of 15 
(iii) Patients, aged at least 18 years old, visiting our pain clinic for chronic pain treatment 
will be recruited because we want to identify a psychological treatment target for 
prescription opioid craving and misuse in patients with chronic pain conditions. 
(iv)We will partner with the Research Participant Engagement Program (RPEP) team for 
Honest Broker outreach. Potential participants are identified via STARR and invited by 
RPEP team (honest broker) on behalf of study team. See Section 16 for Honest Broker 
study invitation letters. We will be using Postal Mail and Research Registry honest 
broker outreach. For Postal Mail, study team may support the process by sticking pre-
printed address labels (created by RPEP, the honest broker) on the envelopes. 
b. 
Age, Gender, and Ethnic Background 
Participants, aged at least 18 years old of both genders and all racial and ethnic 
backgrounds will be included. 
c. 
Vulnerable Populations 
NA 
d. 
Rationale for Exclusion of Certain Populations 
The pain catastrophizing protocols (Taub et al, 2016, Roditi et al, 2009) have been 
validated only for adults with chronic pain. This study will be the first to use this protocol 
in patients taking opioid pain medications for chronic pain management. If this study 
finds no safety concerns in adult patients with chronic pain and chronic opioid therapy, a 
future study can include children. 
e. 
Stanford Populations 
Laboratory personnel, employees, and/or students will not be specifically recruited, 
although they will be able to participate if they visit our clinic. 
f. 
Healthy Volunteers 
NA 
g. 
Recruitment Details 
We will use the Collaborative Health Outcomes Information Registry (CHOIR) system. 
Patients on the CHOIR OK-to-Contact list will be invited to complete the online 
screening survey. Additionally, our lab is affiliated with the Stanford Pain Management 
Center, through which providers can inform interested patients of our research study. If 
needed, we will be able to recruit participants through our existing Stanford research 
databases where participants have agreed to be contacted for future research and recruit 
through community advertisements (Facebook/Instagram, Reddit, Stanford Report, 
Craigslist). 
 
We will partner with the Stanford Research Registry to invite potential arm 1, 2, and 3 
participants from the following cohort lists: 
Individuals 18 and over indicating a pain condition with local zip codes (starting with 94 
or 95) = 211 

02/14/2024 
 
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Individuals 18 and over indicating a pain condition with all zip codes (for arm 3) = 465 
Participants will receive an email invitation (attached in section 16) and then will be 
directed to complete our screening survey. 
 
Potential participants will complete the online screening survey. Based on the screening 
survey results, we will invite eligible participants to a laboratory experiment. 
 
We will partner with the Research Participant Engagement Program (RPEP) team for 
Honest Broker outreach. Potential participants are identified via STARR and invited by 
RPEP team (honest broker) on behalf of study team. See Section 16 for Honest Broker 
study invitation letters. We will be using Postal Mail honest broker outreach. For Postal 
Mail, study team may support the process by sticking pre-printed address labels (created 
by RPEP, the honest broker) on the envelopes. 
 
For both the Postmail and Registry, the patient can either reach out to the research 
coordinator or complete the screening survey. If they reach out to the research 
coordinator, they will send our screening survey link. If they are eligible after completing 
the screening survey, a research coordinator will reach out to conduct a phone screening 
and confirm eligibility. If they complete the screening survey, if they are eligible, a 
research coordinator will reach out to conduct a phone screening and confirm eligibility. 
 
Update 6/6/24: We will use the Pain Division Newsletter, a new IRB approved 
recruitment method for SNAPL, to recruit current and past participants, patients, and 
members of the public who are interested in research on chronic pain. 
h. 
Eligibility Criteria 
i. 
Inclusion Criteria 
For study 1, 2, and 3, 
1. At least 18 years old 
2. Chronic opioid therapy at least 3 months 
3. Any chronic pain conditions at least 3 months 
ii. 
Exclusion Criteria 
For study 1 and 2, 
1. Current diagnosis of cancer 
2. Other severe psychiatric and cognitive conditions (schizophrenia, delusional 
disorder, psychotic disorder, dementia, Parkinson's or dissociative disorder) 
3. An skin conditions on the non-dominant hand (pain testing site) 
4. Non-English speaker 
5. No access to email or smart phone 
6. (For saliva collection) Daily use of cortisol or benzodiazepines 
7. Being pregnant 
8. Needle phobia for blood draw 
9. Current suicide thoughts 
 
added for study 3------------------ 

02/14/2024 
 
Page 9 of 15 
For study 3, 
1. Current diagnosis of cancer 
2. Other severe psychiatric and cognitive conditions (schizophrenia, delusional 
disorder, psychotic disorder, dementia, Parkinson's or dissociative disorder) 
3. Non-English speaker 
4. No access to email or smart phone 
5. Being pregnant 
6. Current suicide thoughts 
7. Concurrent psychological treatments during the 15-day study period. 
i. 
Screening Procedures 
New recruitment method will be used, the Research Participant Engagement Program 
(RPEP). RPEP will use coded diagnoses and procedures, clinical records, demographics 
with embedded identifiers, medications, names, telephone numbers, home address, date 
of birth, date of service, date of diagnosis, emails, and MRNs to recruit via postal mail. 
 
Potentially eligible patients will complete an online prescreening 
survey. The online screening survey will assess patients' chronic pain and other health 
conditions, pain medication use, and prescription misuse, and craving. For prescription 
misuse and craving, the PROMIS item bank for the misuse of prescription pain 
medication and the COMM will be administered. This study will invite people endorsing 
chronic pain at least 3 months, taking opioid pain medications at least 3 months, and no 
craving or craving at any frequency on the PROMIS craving item (i.e., I experienced 
cravings for pain medication). Name, email, and phone number will be collected to invite 
eligible participants for the study. 
 
Based on the responses on the online prescreening survey, potentially eligible patients 
will be contacted via phone for additional explanation about the study and to assess 
eligibility. During the screening phone call, potentially eligible participants will be asked 
questions to ensure inclusion criteria have been met and with the exception of assessing 
for current suicidal thoughts, potential participants will be asked questions to ensure 
exclusion criteria are not met. Participants who are otherwise willing and eligible will be 
notified that there is one sensitive eligibility question that will need to be asked after they 
have provided informed consent. If the potential participant inquires about the eligibility 
question, the research staff will notify the participant that the question is on the topic of 
suicidal ideation and that no response is needed at this time. 
Participants recruited for the Arm 1 and 2 (in-person) study will be invited to the 
laboratory and will receive informed consent. Once the participant has signed the 
informed consent form, the research staff will assess the participant for the exclusion 
criteria of current suicidal thoughts. If the participant reports current suicidal ideations, 
they will be ineligible for the study and the Suicidal Ideation Protocol will be followed 
(included in section 16). Participants found to be ineligible will be withdrawn from the 
study. 
Participants recruited for the Arm 3 (on-line only) study will receive an electronic copy 
of the consent form and will receive information about the study over the phone. Once 
the participant has signed the consent form, the research staff will assess the participant 
for the exclusion criteria of current suicidal thoughts. If the participant reports current 

02/14/2024 
 
Page 10 of 15 
suicidal ideations, they will be ineligible for the study and the Suicidal Ideation Protocol 
will be followed (included in section 16). Participants found to be ineligible will be 
withdrawn from the study. 
j. 
Participation in Multiple Protocols 
Participants will be okay to participate in other clinical trials except for clinical trials 
including pain self-management or psychological interventions. If a patient is interested 
in participating in other clinical trials including pain self-managements or psychological 
interventions, a patient will be informed of two options : the one will be participating in 
other studies after completing this study for 14 days and the other option will be not to 
participate in this study. 
k. 
Payments to Participants 
Participants will be compensated $30 for Study 1, $5 for daily survey for 14 days, $5 for 
three at home saliva samples, and $5 for completion of all study requirement. Therefore, 
when completing the whole study requirements, a participant receive a total of $120. 
 
Travel cost will be compensated: $25 for people living within 60 miles and $50 for 
people living beyond 60 miles. 
 
Added for the Study 3, ------------------------------------------ 
For study 3, participants will be compensated $25 for completing the baseline tasks (the 
30 or 40-min survey, cognitive testing and blood pressure and HR measure), $60 for 
completing the short-daily survey and blood pressure ($5x12 days = $60), and $10 for 
completing a 10-min survey and HR measure at day 8, and $20 for completing the final 
survey. When completing all the tasks, the participant will receive additional $5. 
Therefore, the total compensation is up to $120 (=25+60+10+20+5). Participants will 
receive check as compensation. 
l. 
Costs to Participants 
NA 
m. 
Planned Duration of the Study 
Participants will complete (i) the initial 2.5 hour-laboratory experiment (Study 1) and 
daily home practice of coping statement and daily survey (3-5 minutes, Study 2) for 14 
days. (iii) This study estimates 3 years of data collection and 1 year of data analysis. 
 
Added for study 3,----------------------- 
Participants will completed (i) the initial 45-60min baseline survey, cognitive testing, and 
resting blood pressure and HR measure, (ii) a brief daily survey, resting blood pressure 
and HR measure for 15 days and practicing a 5-min daily coping statement 15 days (only 
for the 50% of people who are assigned to the coping statement condition), (iii) a 10 min 
survey at Day 8 and blood pressure and HR measure, and (iv) 20 min-final survey and 
cognitive testing, and blood pressure and HR measure. 
9. 
RISKS 

02/14/2024 
 
Page 11 of 15 
a. 
Potential Risks 
i. 
Investigational devices 
NA 
ii. 
Investigational drugs 
NA 
iii. 
Commercially available drugs, biologics, reagents or chemicals 
NA 
iv. 
Procedures 
Participants may experience discomfort from blood draw such as bleeding, soreness, 
bruising and stinging at the site of the blood draw. Participants may experience physical 
discomfort in undergoing cold water pressor test. To minimize the risk of physical 
discomfort, we will use our standard laboratory protocol (4 Celsius, 2 minutes), which is 
shown to induce "temporary" discomfort. 
 
Online only Arm 3 study-------------------------- 
No risk of physical discomfort in Arm 3 study 
v. 
Radioisotopes/radiation-producing machines 
NA 
vi. 
Physical well-being 
NA 
vii. 
Psychological well-being 
None of the questionnaires pose a risk to the participants. It is possible that subjects may 
feel uncomfortable answering some questions on the questionnaires; this risk will be 
minimized by allowing participants to refuse to answer a question. Additionally, some 
participants undergo pain catastrophizing induction protocol. We will use a validated pain 
catastrophizing protocol (IRB 11689, Taub et al., 2017, and Roditi et al., 2009), which is 
proven to "temporarily" induce catastrophic thinking about pain. For daily practice of 
pain coping statement, we will have only pain catastrophizing reduction and control 
condition. Finally, we will obtain certificate of confidentiality to protect the privacy of 
research subjects by prohibiting disclosure of identifiable, sensitive research information 
to anyone not connected to the research except when the subject consents or in a few 
other specific situations. 
 
Arm 3 (online only) study-------------------------- 
None of the questionnaires pose a risk to the participants. It is possible that subjects may 
feel uncomfortable answering some questions on the questionnaires; this risk will be 
minimized by allowing participants to refuse to answer a question. Also, we will collect 
the heart rate data anonymously and heart rate data will be recorded only with research 
email account and study id. 

02/14/2024 
 
Page 12 of 15 
 
In this Arm 3 protocol, we have pain catastrophizing reduction and control condition. So, 
the intervention arm may help to reduce catastrophic thinking related to pain. We will 
also ask people to report opioid craving and misuse. As a part of NIH study, certificate of 
confidentiality also apply to this protocol. Therefore, we can protect the privacy of 
research subjects by prohibiting disclosure of identifiable, sensitive research information 
to anyone not connected to the research except when the subject consents or in a few 
other specific situations. 
viii. 
Economic well-being 
<Enter text or "NA"> 
ix. 
Social well-being 
NA 
x. 
Overall evaluation of risk 
Minimum 
b. 
International Research Risk Procedures 
NA 
c. 
Procedures to Minimize Risk 
We are minimizing risks of physiological discomfort by excluding someone with a 
history of vasovagal syncope from blood draw and a needle phobia. We will also check 
vital signs before the blood draw. We are minimizing risks of psychological discomfort 
by allowing participants to refuse to answer any questions. Additionally, we will monitor 
physiological states throughout the study procedures. An experimenter will monitor 
physiological states and make sure their values are all within normal limits by the end of 
the experiment. We will also obtain the certificate of confidentiality to protect the privacy 
of research subjects by prohibiting disclosure of identifiable and sensitive research 
information to anyone not connected to the research except when the subject consents or 
in a few other specific situations. Finally, this study use validated and standard laboratory 
procedures. 
 
For both the in-person study (Arm 1 and 2) and the online-only study (Arm 3), 
participants will be assessed for current suicidal thoughts by research staff after the 
participant has signed the consent form. For the in-person study, the consent procedure 
occurs in-person and participants endorsing current suicidal thoughts will be ineligible 
for the study and the Suicidal Ideations Protocol (included in section 16) will be followed 
accordingly. For the online-only study, participants will be consented over the phone and 
participants endorsing current suicidal thoughts will be ineligible for the study and the 
Suicidal Ideations Protocol (included in section 16) will be followed accordingly. If a 
suicidal thought is expressed anytime even before the consent, we will activate "the 
suicidal ideation protocol." 
 
Added 10/17/2024: In response to the adverse event at the end of September, the research 

02/14/2024 
 
Page 13 of 15 
team will be available to accompany in-person participants to their cars after 
appointments to help ensure their safety. 
 
A research coordinator and research assistant will review all the responses in free text-
format questions daily and activate "The suicide Ideation protocol" as needed. 
d. 
Study Conclusion 
The experiment will terminate when all data has been collected from participants. An 
individual's participation will terminate at the point that all data is collected from that 
individual, if the protocol director decides to withdraw the subject, or if the patient 
wishes to withdraw from the study. 
e. 
Data Safety Monitoring Plan (DSMC) 
i. 
Data and/or events subject to review 
Self-reported adverse events were collected at the study endpoint for Aim 1, 2, and 3 
studies. Adverse events were reviewed as soon as participants reported any events on 
the REDCap, which sent automatic email notification to Dr. You, PI and Clinical 
Research Coordinator.  
ii. 
Person(s) responsible for Data and Safety Monitoring 
Dokyoung Sophia You, PhD 
iii. 
Frequency of DSMB meetings 
Yearly 
iv. 
Specific triggers or stopping rules 
Any SAEs that are probably or possibly related to this study 
v. 
DSMB Reporting 
Sent a yearly DSMB reporting to NIH 
vi. 
Will the Protocol Director be the only monitoring entity? (Y/N) 
Y 
vii. 
Will a board, committee, or safety monitor be responsible for study monitoring? 
(Y/N) 
N 
f. 
Risks to Special Populations 
NA 
10. 
BENEFITS 
There is no direct benefit to the participants. Knowledge gained from this study may help to 
identify a psychological treatment target to reduce prescription opioid craving and misuse, and 

02/14/2024 
 
Page 14 of 15 
therefore,  
psychological treatments to reduce prescription opioid craving can help patient with chronic pain 
to use pain medication as prescribed or successfully taper the medication as recommended by a 
doctor. This study also has the potential to inform that other psychological interventions 
(cognitive and behavioral therapy for pain and mindfulness), which are known to reduce pain 
catastrophizing, will be effective in improving medication compliance and success of 
prescription opioid tapering. 
11. 
PRIVACY AND CONFIDENTIALITY 
All participant information and specimens are handled in compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and privacy policies of Stanford University, Stanford 
Health Care, and Stanford Children’s Health. 
 
 
 

02/14/2024 
 
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Analysis Plan 
We will conduct two-way repeated-measures ANOVAs (Condition × Time) to test whether reductions in 
pain catastrophizing are associated with decreases in craving, cortisol levels, and psychological distress 
(depression and anxiety). 
 
If a significant effect of Condition is observed, we will conduct mediation analyses to test whether the 
intervention’s effects on craving are mediated by reductions in cortisol and psychological distress.