Clinical trial NCT03224468
Conditions: Pain Insomnia Depression Anxiety
Keywords: medical marijuana cannabis pain insomnia depression anxiety addiction dependence neurocognition MRI
Sponsor: Massachusetts General Hospital
Start date: 2017-07-01; Completion date: 2022-11-01
Enrollment: 269 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will use a randomized controlled design to test whether patients who use medical marijuana, compared to a waitlist control group, experience a change in health outcomes (relief of symptoms, or adverse health outcomes such as new-onset symptoms of cannabis use disorders, neurocognitive impairments) or brain-based changes.

Detailed description:
This trial is a randomized, longitudinal study of medical marijuana (MM) that will: (1) characterize the impact of MM on indices of addiction, such as CUD, escalation of use, tolerance, and withdrawal among those who stop using, (2) assess, via dosing diaries, the effect of MM use patterns on use of other medications, and perception of underlying disease symptomatology, (3) characterize the impact of MM on neurocognitive performance, including executive function, memory, attention, and decision-making and (4) examine evidence for impact of MM on brain structure and function. This study will enroll 200 adults with no prior history of CUD or heavy marijuana use, who express interest in using MM to treat pain, insomnia, anxiety, and/or depression. Participants will be randomly assigned to either an active MM arm (n = 100), or to a waitlist control arm (WLC) (n = 100). Participants will be assessed at baseline, regularly for 3 months, and at a 6-month and 12-month follow-up for MM use behaviors, development of CUD, perception of disease symptomatology, and neurocognitive performance. Urine collected at each visit will be assessed with quantitative assays. MRI scans will be collected to longitudinally investigate possible brain changes associated with MM use.

Arms: arm 1: This group can begin using medical marijuana immediately. arm 2: This group agrees to wait 3 months before using medical marijuana.
Interventions: intervention 1: Medical Marijuana
Intervention descriptions: intervention 1: Patients in this group can choose when, where, and how much medical marijuana to use.

Protocol documents:
Prot_SAP_000.pdf: 
Effect of Medical Marijuana on Neurocognition and Escalation of Use
NCT03224468
Date: 1/28/2022


PARTNERS HUMAN RESEARCH COMMITTEE 
 
DETAILED PROTOCOL: Effect of Medical Marijuana on Neurocognition and Escalation of Use 
Protocol #: 2015P001600 
Principal Investigator: Jodi Gilman, Ph.D. 
Co-Investigator: A. Eden Evins, MD 
 
 
Summary of Changes Made and Rationale 
 
The IRB protocol, attached, was written for a pilot phase of the trial, and was updated when we 
received the R01. All measures, outcome definitions, and sample size calculations were up to 
date in clinicaltrials.gov (NCT03224468). The statistical analysis section was amended before 
any data were analyzed except for the propensity score analysis for missing data, explained 
below. No changes were changed after looking at the data, except for the propensity score 
analysis.  
 
Method of randomization:  
In Year 1 of the study, we realized that many participants, who were interested in obtaining an 
MMC never obtained one because of barriers such as expense or needing to go outside the 
usual healthcare system. We therefore changed our randomization from 1:1 to 2:1 MMC:WLC 
early in the trial in order to have enough participants in the MMC arm. 
 
Outcomes and outcome definitions:  
Outcome measures and definitions were updated on 07/19/2017 in clinicaltrials.gov 
(NCT03224468), but were not explicated stated in the IRB protocol. 
 
Primary Outcome Measures: 
- 
Cannabis Use Disorder Symptoms (Time Frame: Baseline to 12 Weeks)  
o The DSM-5 Cannabis Use Disorder Checklist will evaluate symptoms of CUD 
(number of symptoms). 
- 
Changes in Symptoms of Depression and Anxiety (Time Frame: Baseline to 12 Weeks) 
o For those with depression and anxiety symptoms, the Hospital Anxiety and 
Depression Scale will be used to assess symptoms. 
- 
Changes in Pain (Time Frame: Baseline to 12 Weeks) 
o For those with pain, the Brief Pain Inventory Severity Scale (BPI-S) will be used 
to assess levels of pain. 
- 
Changes in Sleep (Time Frame: Baseline to 12 Weeks) 
o For those with insomnia, the Athens Insomnia Scale will be used to assess 
symptoms. 
 
Secondary Outcome Measures  
o General Medical/Psychiatric Health (Time Frame: Baseline to 12 Weeks) The 
Short Form-12 Health Survey (SF-12) will be used to assess self-report of 
emotional and physical functioning. 
- 
Cognitive Testing (Time Frame: Baseline to 12 Weeks) 
o Verbal learning/memory, attention, working memory, and complex decision-
making will be assessed. 
- 
Brain-based Measures (Time Frame: Baseline to 1 Year) 


o Changes in resting state functional connectivity and task-associated activation in 
brain regions involved in reward, inhibitory control, and working memory will be 
assessed. 
 
The IRB protocol includes exploratory outcomes that were not presented in this manuscript, but 
will be included in future publications. 
 
Statistical Analysis: The IRB protocol did not include the final statistical plan. When we 
brought Dr. David Schoenfeld, an experienced clinical trial statistician, on this project in Year 2 
of the study, well before any analysis had been conducted, he suggested that instead of a 
random slopes analysis that assumes the effect of the drug will be to gradually increase the 
effect or outcome, ie a time x treatment interaction, he suggested we should assume a constant 
treatment effect over the follow up period, 2 weeks, 1 month, 3 months. Dr. Schoenfeld also 
advised us not to adjust for covariates as we originally proposed to do, but to only adjust for 
baseline symptoms, since randomization should have accounted for differences and we had no 
strong prior information about what covariates would have an important effect on CUD in people 
seeking cannabis for medical complaints. Dr. Schoenfeld, without access to the data, made 
these recommendations to Drs Gilman and Evins after which Dr. Potter, who had access to the 
data, implemented the analyses.  
 
Propensity score analysis for missing data: We could not ensure that participants in the 
MMC condition obtained an MMJ card, and we could not give participants a MMJ card because 
of state and hospitals regulations, a stated limitation of the study. Thus, we conducted a post 
hoc sensitivity analysis to verify the positive findings of the primary analysis in the final stages of 
the analysis when we realized that there was a problem with differential drop-out between the 
randomization and the baseline visit in the MMC and WLC groups.  
 
Sample size calculation: 
This was not included in the trial protocol but calculated for the R01 grant submission in 2016.  
We aimed to recruit 200 participants in order to have sufficient power to detect benefits and 
risks of MMCs. To identify a difference in development of CUD symptoms in the MMC vs WLC 
groups, assuming that the mean number of symptoms for MMC would be .4 (corresponding to 
20% of subjects developing CUD) versus .1 in WLC (corresponding to 5% of subjects 
developing CUD), at a two-sided 0.05 significance level, power was 85%. To identify a 
difference in symptoms of pain, insomnia, depression, and anxiety, assuming a clinically 
significant effect would be a 30% reduction in presenting medical symptom with MMC while 
WLC subjects were expected to have a minimal change, assumed to be a 5% reduction, at a 
two-sided 0.05 significance level, based on effect sizes in the literature, power was 84% (pain), 
90% (insomnia), and 84% (depression and anxiety), with sample sizes of approximately 1/3 (33 
in each group) in the pain, insomnia, and anxiety/depression subgroups.  
 
 


 
1 
PARTNERS HUMAN RESEARCH COMMITTEE 
 
 
DETAILED PROTOCOL: Effect of Medical Marijuana on Neurocognition and Escalation of Use 
Protocol #: 2015P001600 
Principal Investigator: Jodi Gilman, Ph.D.  
Co-Investigator: A. Eden Evins, MD 
Version Date: 04/15/2020 
 
I. BACKGROUND AND SIGNIFICANCE 
Cannabis is the most commonly used illicit substance in the United States, particularly among 
young people, and prevalence estimates are steadily increasing 1. Recent estimates suggest that 
52% of 18 to 25 year olds have ever tried cannabis2, and 23.4% of high school students reporting use 
one or more times per month3. Delta-9-tetrahydrocannabinol (THC), the psychoactive compound in 
cannabis, binds to endogenous cannabinoid CB1 receptors located in brain regions such as the 
hippocampus, amygdala, basal ganglia, prefrontal cortex, substantia nigra and globus pallidus 4,5, 
making frontal-limbic neurocircuitry particularly susceptible to cannabis-related effects in the brain6. 
There is now a well-established relationship between regular cannabis use and a range of potentially 
adverse outcomes, including effects of learning and cognition (see 7,8 for review), effects on brain 
structure and function (see 9 for review), and potential impacts on mental health (10). Furthermore, 
regular cannabis use can lead to the development of cannabis abuse or dependence [11,12], 
particularly among daily users, where it is estimated that between 25-50% of users will develop a 
substance use disorder (13). A recent study found that younger age of onset of regular and maximum 
daily use were correlated with lower achievement scores and worse neurocognitive functioning14. 
At the time of this submission, 23 states have legalized marijuana for medical use. Virtually 
nothing is known about the effects of marijuana on those who choose to use marijuana for medical, 
and not recreational, purposes. Healthcare providers will be increasingly confronted with patients who 
are interested in using medical marijuana (MM) to treat various disorders, and few evidence-based 
studies exist to offer guidance regarding side effect profiles for these patients. Basic behavior 
regarding use of MM, including whether patients substitute MM for traditional medicines, resulting in 
reductions in use of opiates or other medications, is not known. Little is known about tolerability, 
amounts, duration of use, or whether patients reach a stable and regular dose of MM. As extensive 
research has shown that marijuana can affect memory, attention, decision-making, and even IQ, it is 
important to study whether or not those who use MM experience neurocognitive harms. Data is also 
lacking on whether those who use MM daily for chronic conditions also develop similar rates of 
addiction to those who use marijuana daily for recreational purposes.  
It is important to study, in a rigorous and well-controlled manner, (1) basic behavior of MM 
patients, including general patterns of MM use, tolerability, dose (e.g. stable vs escalation of use), 
perception of benefit for presenting medical condition, and change in maintenance medication use 
(e.g. reduction/discontinuation in opiate use), (2) progression to addiction and escalation of use, 
including an experience loss of control over intake of marijuana or other substances, development of 
tolerance, marijuana caving, and experience of reinforcing effects (e.g. euphoria or ‘high’), and 
withdrawal among those who choose to stop using marijuana, and (3) side effect profiles of medical 
marijuana on neurocognition, including memory, attention, and executive function, as well as possible 
effects on neural structure and function.  
 
II. SPECIFIC AIMS 
Aim 1: To observe behavior of MM patients in first months of use, including potential 
progression to addiction. We will examine, using rigorous real time daily dosing/purchase diaries, 
temporal patterns of MM use and change over time (e.g. stable vs escalation of use), tolerability, 
perception of benefit for presenting medical condition using EMA techniques, and change in 


 2 
dose/frequency, type of maintenance medication use (e.g. reduction/discontinuation in opiate use) 
also with real time, daily diaries. We will also examine whether or not MM patients experience loss of 
control over intake of marijuana or other substances. We will use measures such as development of 
tolerance, escalation of use, marijuana caving, and assess experience of reinforcing effects (e.g. 
euphoria or ‘high’), and withdrawal among those who choose to stop using marijuana.  
 
Any changes throughout 12 months in perception of disease symptomatology or in use of 
maintenance medication will be compared to the waitlist control group. 
 
Aim 2: To assess neurocognitive and psychiatric effects of MM. We expect that neurocognitive 
outcomes, such as working memory, attention, executive function, anhedonia, amotivation, and 
decision-making, (when not acutely intoxicated) may be worsened with MM use. Outcomes may be 
worse in those who use more frequently/heavily (as measured by quantitative THC screens and 
dosing dairies). 
 
Aim 3: In a subset of patients, assess how MM effects neurocircuitry of prefrontal function. We 
will use functional MRI tasks to assess working memory, inhibitory control, sustained attention, and 
risk/reward task performance and brain activation patterns. We expect that individuals who use MM 
may experience changes from baseline in neurocircuitry involved in memory, attention, inhibitory 
control and reward.  
 
Aim 4: To assess how medical marijuana patients compare to healthy controls in structural 
and functional brain imaging measures. We will use functional MRI tasks to assess memory, 
inhibitory control, sustained attention, and risk/reward task performance and brain activation patterns. 
We expect that individuals who use MM to show alterations in task-related brain activity. 
 
III. PARTICIPANT SELECTION 
 
Medical Marijuana Participants 
Inclusion Criteria: 
1. Men and women aged 18-65 years, inclusive;  
2. Competent and willing to provide written informed consent;  
3. Desire to use medical marijuana for self-reported pain, sleep, or affective (mood and/or anxiety 
including PTSD) symptoms. 
4. Not in possession of a medical marijuana card, but expressing intent to get one. 
5. Able to communicate in English language.  
 
Exclusion Criteria: 
1. Current daily marijuana use (prior to enrollment) 
2. Current substance use disorders (e.g. cocaine, opiate, stimulant). Light to moderate alcohol use is 
permitted (defined as 16 or less on the AUDIT), and nicotine dependence is permitted because of the 
high co-use of nicotine and marijuana. Participants cannot meet current SCID criteria for a use 
disorder on any illicit substance.  
3. Pregnant (verified by a urine test). 
4. Diagnosis of acute coronary syndrome, coronary thrombosis, myocardial infarction, 
cardiomyopathies and arrhythmias such as atrial fibrillation, ventricular tachycardia or fibrillation, 
thrombophilia such as Factor V Leiden, Prothrombin 20210, antithrombin deficiency, Antiphospholipid 
syndrome. 
5. History of deep vein thrombosis (DVT), pulmonary embolism, stroke.  
6. In the opinion of the investigator, not able to safely participate in this study because of any medical 
or psychological issues (e.g. psychosis) that might compromise their safety. 


 
3 
Healthy Control Participants 
Inclusion Criteria: 
1. Men and women aged 18-65 years, inclusive 
2. Competent and willing to provide written informed consent 
3. Able to communicate in English language 
4. No contraindications for fMRI (see MRI safety screening form). 
 
Exclusion Criteria: 
1. Current or past history of major medical illness by self-report 
2. History of diabetes, cardiovascular disease, HIV, Hepatitis C, migraines, head injury or prolonged 
unconsciousness (> 24 hours) 
3. Current use of drugs/medications, such as analgesics 
4. Current use of illicit drugs, verified with urine drug screen 
5. Pregnancy, verified with urine screen 
6. Meets DSM-5 criteria for psychological disorders (current) 
7. Reports using marijuana in the past 3 months 
8. Reports using marijuana approximately > 50 times in their lifetime 
9. In the opinion of the investigator, not able to safely participate in this study. 
 
Healthy Control Participants and Medical Marijuana Participants to Undergo MRI Scanning 
Additional Inclusion Criteria for MRI studies (applicable for only the subset who will undergo 
neuroimaging) 
1. Randomized to active MM group or scanned as healthy control participants. 
 
Additional Exclusion criteria for MRI studies (applicable for only the subset who will undergo 
neuroimaging) 
1. Known claustrophobia 
2. Presence of electrically, magnetically, or mechanically activated implants (such as cardiac 
pacemakers) or intracerebral vascular clips 
3. History of working with metal (e.g. shavings or fragments could be lodged in scalp or eye) 
4. Pregnancy (if the subject cannot rule out the possibility of pregnancy, a pregnancy test will be 
conducted prior to the study) 
5. In the opinion of the investigator, not able to safely participate in this study.  
 
 
IV. RECRUITMENT METHODS 
Participants will be recruited by study staff at the MGH Center for Addiction Medicine through 
advertising by email, web and bulletin board announcements posted within the local site network 
community. We will place a Partners HRC approved research study advertisement on relevant 
websites and in relevant print publications, as well as on the MBTA and on radio advertisements. We 
will also recruit from local clinics. 
 
In accordance with NIH guidelines, efforts will be made to attain a mix of study participants, in terms 
of gender and racial/ethnic representation that is reflective of the population of the greater 
metropolitan area where the recruitment is taking place.  For example, for the metropolitan Boston 
area we will attempt to recruit; 63% white, 26% African American and 11% other races. We anticipate 
that half of our participants will be male and half female and that we will have representation from 
Asian American, African American and Hispanic minority groups in our final cohort that is 
representative of that reported in census data for Greater Boston. 
 
 


 4 
V. STUDY PROCEDURES 
Healthy Control Participants 
Screening: Participants who have expressed interest in participating in the study will undergo a brief  
phone screen to assess eligibility. We plan to phone screen about 100 participants. If they are eligible 
according to the phone screen, they will be scheduled for an in-person study visit. At this visit, a 
consent form will be reviewed with the study doctor. If participants are determined eligible at the end 
of this visit, they will then be scheduled for the MRI scan.  
 
Study Design: 
Visit I: Healthy Control Screen 
 
Visit I of this study will take place outside of the scanner only. Participants will be recruited and 
scheduled for a behavioral session. In this session, we will test participants on a computer in order to 
optimize the parameters of the task.   
 
Visit II.  Healthy Control Imaging Procedure 
 
In Visit II, participants who have met all inclusion criteria and none of the exclusion criteria will be 
scheduled for an MRI scan.  Each scan session will last up to two hours during which structural 
and/or functional images will be collected.  
 
Participants will be positioned in the scanner and outfitted with audio and visual presentation and 
response indicator equipment. Visual images and auditory stimuli will be presented using MRI 
compatible presentation software and hardware. Participant responses are monitored using MRI-
compatible keypads, and reaction times may be recorded for subsequent analysis of timing and 
accuracy of task performance. 
 
 
 
Visit I 
Visit II 
Measure 
Instrument 
Screen 
MRI Scan 
General Medical/Psychiatric Health 
 
 
 
 
 Medical History/ CON MEDS 
 
x 
 
 Drug Screen/pregnancy 
 
x 
x 
 Psychiatric Interview 
MINI 7 
x 
 
 Suicidality and Health Risk Taking 
  (N/A for scores < 9 on MINI Suicidality) 
CHRT 
x 
 
 Provider Expectations for 
 Recovery Scale 
PERS 
x 
 
Substance Use 
 
 
 
 Frequency of substance use 
TLFB (MJ, EtOH, tobacco, other 
drugs) 
x 
 
 Harmful drinking  
AUDIT 
x 
 
Cognitive Testing 
 
 
 
   Intelligence / reading 
WTAR 
x 
 
MRI Scan 
 
 
 
   MPRAGE 
Structural 
 
x 
   Resting state  
Functional connectivity 
 
x 
   Task-based (i.e. working  
   memory, inhibitory control) 
Task-based fMRI 
 
x 
 
MRI Protocol: The purpose of the MRI portion of the study is to compare the brains of individuals 
with no serious medical conditions, current psychological conditions, or drug use to those enrolled in 
the medical marijuana study. All of these participants will undergo a 3T MRI scanning. Each scan 
session will last up to two hours during which structural and functional data will be collected. 


 
5 
Participants will be positioned in the scanner and outfitted with audio and visual presentation and 
response indicator equipment. Visual images and auditory stimuli will be presented using MRI 
compatible presentation software and hardware. Participant responses are monitored using MRI-
compatible keypads, and reaction times may be recorded for subsequent analysis of timing and 
accuracy of task performance. 
Participants may undergo the scans noted below: 
 
1.   Structural MRI 
For the structural imaging sessions T1 -weighted sequences may be acquired. Multiple 
anatomical imaging sequences may be run to assess specific image quality measures. The 
same anatomical scans will be repeated varying a limited range of pulse sequence 
parameters to assess their effect on the image contrast, image artifacts and signal to noise 
ratio. Parameters that will be varied may include the repetition time of the MR acquisition (TR), 
the echo time of the acquisition (TE), and the presence of pre-acquisition inversion pulses. 
The above parameters will also be evaluated in pulse sequences which acquire parameters 
used in the reconstruction of the MR images. The software and hardware interlocks put in 
place by the scanner manufacturer ensures that the range of these parameters will be 
maintained within the FDA's non-significant risk criteria.  
 
2.  Functional Magnetic Resonance (fMRI) 
The scanner is outfitted with audio and visual presentation and response indicator equipment. 
All tasks are programmed using presentation software that is synchronized with the video 
synch pulse of the computer running the task.  The presentation software also collects the 
behavioral response information. The experimental paradigms will assess activation in brain 
regions underlying memory, attention, inhibitory control, and risk/reward. Participants may 
earn points for correct answers, and those points may be converted to monetary values. The 
experimental paradigm will take approximately 45 minutes to complete. We will also assess 
resting-state functional connectivity using standard FC-MRI sequences. The entire scan will 
last about one hour. 
 
Drug Testing: At both study visits, participants will provide a urine sample, which will be used to 
qualitatively screen for cannabis use as well as other substances of abuse. An alcohol reading may 
also be taken if there is any concern about a participant being intoxicated. 
 
Medical Marijuana Participants 
Screening: Participants who have expressed interest in participating in the study will undergo a brief 
phone screen to assess eligibility. We plan to phone screen about 2000 participants. If they are 
eligible according to the phone screen, they will be scheduled for an in-person (or teleconference) 
study visit. At this visit, a consent form will be reviewed with the study staff. Participants who give 
permission to receive text messages from the study staff will receive appointment reminders via text 
two days before upcoming appointments. In addition, subjects will be instructed on how to use our 
phone app for tracking their medical marijuana use, they will fill out some questionnaires and also do 
a urine drug and if applicable, a pregnancy test.  Also at this visit, participants will be randomized to 
either the active study group or the waitlist control group. We plan to randomize 200 participants to 
each group.  
 
Study Design: The active study group will be asked to call the study staff once they receive their MM 
cards. A staff member will follow up via phone with participants who do not contact study staff within 
approximately two weeks after the screening visit. Staff will contact participants again after 
approximately four weeks and six weeks to check in on the status of the medical marijuana card 
application. If after six weeks, a participant still has not made any progress on the application for a 


 6 
medical marijuana card (i.e., made an appointment with a doctor who recommends medical 
marijuana), the participant will be discontinued from the study and a three-month follow-up visit will be 
scheduled.  
 
When participants in the active study group receive their medical marijuana card, they will be 
scheduled for a baseline assessment in which they will undergo cognitive testing, interviews, 
questionnaires, and possibly an MRI scan (see Measures below). In contrast, participants in the 
waitlist control group will be scheduled for the baseline visit approximately 3-4 weeks following the 
screening visit. All participants will then be scheduled for repeat assessments at approximately 2 
weeks, 1 month, 3 months, 6 months and 1 year after the baseline visit. All participants will receive 
monthly check in phone calls from a research coordinator at approximately 2, 4, 5, 7-11 months past 
baseline in order to update study staff on medication changes, recent substance use, and overall 
physical and mental health. Participants will also be asked to complete a 2-year follow-up phone call, 
which is identical to previous check in calls, with the addition of the CGI and CUD checklist. If 
participants are in the active study group, we will ask that they not use MM on the day of testing 
(though they can use it after testing on that day). These visits will take approximately 3 hours to 
complete. 
 
In consultation with their prescribing physician, participants in the waitlist control group will be asked 
to wait to start using MM until they have completed Visit 5 (Three Months). During those 3 months, 
they will be assessed at the same time points as those in the active MM group (see study schema). 
After the 3-month waitlist period, the waitlist control group will have the option to start using MM. If 
this group fails to adhere to the waitlist control, they will be kept in the study and will be asked to 
complete the same assessment schedule as those initially assigned to the active study group. All 
participants will be assessed after 1 year.  
 
 
 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Measure 
Instrument 
Screen 
Baseline 
Two 
Weeks 
One 
Month 
Three 
Months 
Six 
Months 
One 
Year 
General Medical/Psychiatric Health 
Medical History/ CON MEDS 
 
x 
x 
x 
x 
x 
x 
x 
Quantitative cannabinoids 
 
 
x 
x 
x 
x 
x 
x 
Drug Screen/pregnancy 
 
x 
x 
x 
x 
x 
x 
x 
Psychiatric Interview 
MINI 7 + Past 
SUD and AUD 
x 
 
 
 
 
 
x 
Suicidality and Health Risk 
Taking 
CHRT 
x 
x 
x 
x 
x 
x 
x 
Emotional and physical   
Functioning 
SF-12 
 
x 
x 
x 
x 
x 
x 
ADHD symptoms  
ASRS 
 
x 
 
 
 
 
x 
Impulsivity  
BIS-11 
 
x 
 
 
x 
x 
x 
Executive function 
BRIEF 
 
x 
 
 
x 
x 
x 
Risk perceptions and behavior  
DOSPERT 
 
x 
 
 
x 
 
 
Family history of Addiction  
KSADS  
x 
 
 
 
 
 
 
Provider Expectations for  
Recovery Scale 
PERS 
x 
 
 
 
 
 
 
Substance Use 
Frequency of substance use 
TLFB (MJ, EtOH, 
tobacco, other 
drugs) 
x 
x 
x 
x 
x 
x 
x 
monthly check in phone calls 
2-yr follow-up call 


 
7 
Cannabis Use Disorder Screen 
DSM-5 Cannabis 
Use Disorder 
Checklist 
x 
x 
x 
x 
x 
x 
x 
MJ craving  
MCQ-SF 
 
x 
x 
x 
x 
x 
x 
Marijuana Motives 
MMM 
 
 
 
 
x 
 
 
Marijuana Withdrawal (if stop) 
CWS 
 
x 
x 
 
x 
x 
x 
MJ use severity 
CUDIT 
 
x 
x 
x 
x 
x 
x 
Harmful drinking  
AUDIT 
x 
 
 
 
x 
x 
x 
Alcohol consumption urge  
URGE 
 
x 
x 
x 
x 
x 
x 
Expectancy of MMJ effects  
MMEEQ 
x 
x 
 
x 
x 
x 
x 
Reflection of MMJ effects 
(qualitative) 
 
 
 
 
 
 
 
x 
x 
Symptoms 
Pain level 
BPI 
x 
x 
x 
x 
x 
x 
x 
Pain Catastrophizing Scale 
PCS 
x 
x 
x 
x 
x 
x 
x 
Perceived Stress Scale 
PSS 
x 
x 
x 
x 
x 
x 
x 
Clinician’s Severity Scale 
CGI 
 
x 
x 
x 
x 
x 
x 
Insomnia  
AIS 
x 
x 
x 
x 
x 
x 
x 
Anxiety Scale  
HADS 
x 
x 
x 
x 
x 
x 
x 
Delusions and Psychosis  
PDI 
 
x 
 
x 
x 
x 
x 
Difficulties due to health  
conditions 
WHODAS 
x 
x 
 
 
x 
x 
x 
Post-traumatic stress symptoms 
PCL 
x 
 
 
 
 
 
x 
COVID-19 Specific Questionnaires 
Remote Pre-Visit Form 
PVF 
x 
x 
x 
x 
x 
x 
x 
Effects of COVID-19 pandemic 
on mood, pain, sleep, lifestyle 
COVID Impact 
x 
x 
x 
x 
x 
x 
x 
Impact of epidemic/pandemic 
on various areas of life 
EPII 
x 
 
 
 
 
 
 
Changes in substance use 
since COVID-19 pandemic 
Covid19-CSU 
x 
 
 
 
 
 
 
Cognitive Testing 
Verbal learning/memory,  
attention, working memory,  
and complex decision-making  
CANTAB 
 
x 
 
x 
x 
x 
x 
Intelligence / reading 
WTAR 
x 
 
 
 
 
 
 
MRI Scan 
MPRAGE 
Structural 
 
x 
 
 
 
 
x 
Resting state  
Functional 
connectivity 
 
x 
 
 
 
 
x 
Task-based (i.e. working 
memory, inhibitory control) 
Task-based fMRI 
 
x 
 
 
 
 
x 
 
Drug Testing: At all study visits, participants will provide a urine sample, which will be used to 
qualitatively screen for cannabis use as well as other substances of abuse. For participants who 
provide written consent for sample shipment, urine samples will be shipped to quantitatively screen 
for amount of THC metabolites in urine. Samples will only be shipped for participants who report 
recent marijuana use and/or qualitatively screen positive for THC. An alcohol reading may also be 
taken if there is any concern about a participant being intoxicated.  
 
Urine Collection During Remote Data Collection: While we must conduct remote study visits, 
participants will be asked to consent to shipping their urine samples to study staff for analysis of 
cannabinoid metabolites. Participants who do not consent to remote urine collection will not be 
penalized and will not receive materials for shipping their urine for testing. Participants who consent 


 8 
will receive urine sample kits by mail prior to their remote visits. Kits include a sample cup, biohazard 
bag, packaging bag, UPS shipping bag, and detailed instructions on how to provide and package 
their urine sample. Participants will be instructed to leave the packaged sample at the location where 
their mail is picked up at their home before the scheduled pickup time. Because there is no staff at 
our MGH offices, study staff will schedule a UPS pickup for overnight shipping from the participant’s 
home to the home of our Center Director, Dr. Eden Evins, MD, who will be available to transport urine 
samples to the -80 degree freezer in the Thier Building on the MGH campus for storage prior to batch 
transport to Colorado for analysis of cannabinoid metabolites central to understanding the primary 
outcomes of the study. Dr. Evins will pipette aliquots of samples into labeled vials for freezer storage. 
Samples will be batch shipped on dry ice to Colorado when that lab is again functioning at its capacity 
and able to conduct quantitative assay for cannabinoid metabolites per study protocol. Dr. Evins is 
approved as Emergency Level 4 Research Staff Essential Personnel, and as such has access to the -
80 degree freezer in the Their Research building, as per guidance from hospital leadership. Drs. 
Gilman and Evins, and 2 other members of study staff also have this approval and can take over this 
urine aliquoting and transport task should Dr. Evins be unable to perform it due to illness or 
redeployment. 
 
Online Dosing Diaries: All participants will be asked to keep a daily log of (1) marijuana use, and (2) 
ratings of pain, sleep quality, mood, and general health. They will be asked to send in data once per 
day during the first three months of study participation (from Visit 1 to Visit 5). We will collect this data 
using Secure Survey, a web application designed to collect data from a modern user group on their 
mobile, tablet, or desktop devices.  
 
MRI Protocol (Optional): The purpose of the MRI portion of the study is to investigate possible 
changes in the brain from those who obtain MM cards. Therefore, only patients randomized the active 
MM group will be given the option to undergo a 3T MRI scanning. Participants will undergo MRI 
scanning at baseline and at 1 year after initiation of MM. In addition, a small group (n = 25) of non-
MJ-using controls, matched on demographics, will also be scanned at baseline and after 1 year in 
order to allow us to assess normative change over time. Each scan session will last up to two hours 
during which structural and functional data will be collected. Participants will be positioned in the 
scanner and outfitted with audio and visual presentation and response indicator equipment. Visual 
images and auditory stimuli will be presented using MRI compatible presentation software and 
hardware. Participant responses are monitored using MRI-compatible keypads, and reaction times 
may be recorded for subsequent analysis of timing and accuracy of task performance.  
Participants may undergo the scans noted below: 
 
1.   Structural MRI 
For the structural imaging sessions T1 -weighted sequences may be acquired. Multiple 
anatomical imaging sequences may be run to assess specific image quality measures. The 
same anatomical scans will be repeated varying a limited range of pulse sequence 
parameters to assess their effect on the image contrast, image artifacts and signal to noise 
ratio. Parameters that will be varied may include the repetition time of the MR acquisition (TR), 
the echo time of the acquisition (TE), and the presence of pre-acquisition inversion pulses.  
The above parameters will also be evaluated in pulse sequences, which acquire parameters 
used in the reconstruction of the MR images. The software and hardware interlocks put in 
place by the scanner manufacturer ensure that the range of these parameters will be 
maintained within the FDA's non-significant risk criteria.  
 
2.  Functional Magnetic Resonance (fMRI) 
The scanner is outfitted with audio and visual presentation and response indicator equipment. 
All tasks are programmed using presentation software that is synchronized with the video 


 
9 
synch pulse of the computer running the task.  The presentation software also collects the 
behavioral response information. The experimental paradigms will assess activation in brain 
regions underlying memory, attention, inhibitory control, and risk/reward. Participants may 
earn points for correct answers, and those points may be converted to monetary values. The 
experimental paradigm will take approximately 45 minutes to complete. We will also assess 
resting-state functional connectivity using standard FC-MRI sequences. The entire scan will 
last about one hour. 
 
 
V. REMUNERATION 
Healthy Control Participants 
Participants in the healthy control group will be paid for the completion of each study visit. Each study 
visit is compensated in the amount of $50. If participants undergo the screening visit but are not 
eligible, they will be paid $20 for the first visit only. There are opportunities to receive additional 
money in the MRI scanner ($1- $50) based on scan task performance. All participants who drive to 
visits will also be given parking vouchers for each visit. This level of compensation is deemed 
appropriate given the time commitment. All payments will be made via check following each study 
visit. 
 
 
Medical Marijuana Participants 
Participants in the medical marijuana study will be paid after the completion of each study visit, and 
weekly for submitting their dosing diaries. Participants will be compensated $20 on the day of the 
screen and $60 for each study visit. Participants will be paid an additional $40 after completing their 
six month visit and an additional $60 after completing their twelve month visit. Participants will be paid 
$10 for completing seven monthly 10-minute check in phone calls at months two, four, seven, eight, 
nine, ten and eleven with a research coordinator. The purpose of these phone calls is to record AEs, 
medication changes, TLFB, and symptom severity (measured by the SF-12). Participants will be paid 
an additional $5 for completing the EPII and $5 for completing the Covid19-CSU.  If participants 
undergo the screening visit but are not eligible, they will be paid $20 for the first visit only. They will be 
paid $20 per week for submitting dosing diaries during the first three months of the study, for a 
maximum total of $260 for completing all dosing diaries. Additionally, they may be paid for pre-
baseline daily diary entries for a maximum of five weeks ($20 per week, $100 total). They will be paid 
$50 for each scan if they agree to undergo scanning procedures. For each scan participants may also 
receive additional money ($1-100) based on scan task performance. All participants who drive to 
visits will also be given parking vouchers for each visit. All payments will be made via check at the 
end of the study.  
 
Please see table below for payment schedule. 
Visit # 
Active Study Group 
Waitlist Control Group 
1 
Screening 
$20 
Screening 
$20 
2 
Baseline 
$60 
Baseline 
$60 
3 
2 weeks 
$60 
2 weeks 
$60 
4 
1 month 
$60 
1 month 
$60 
5 
3 months 
$60 
3 months 
$60 
 
Dosing Diaries 
(13 weeks x $20/week) 
$260 
Dosing Diaries 
(13 weeks x $20/week) 
$260 
6 
6 months 
$100 
6 months 
$100 


 
10 
 
Monthly phone calls 2, 4, 7-11 
months (7 x $10 each) 
$70 
Monthly phone calls 2, 4, 7-11 
months (7 x $10 each) 
$70 
 
Covid19 Questionnaires 
$10 
Covid19 Questionnaires 
$10 
12 
12 months 
$120 
12 months 
$120 
Total 
 
$820 
Total 
$820 
Scan 
(Optional) 
Baseline 
$50 
 
 
 
12 months 
$50 
 
 
Total 
 
$920 
 
 
 
 
VI. PARTICIPANT ENROLLMENT 
 
MGH Study staff will conduct telephone screening of potential subjects.  A telephone screening will 
distinguish the majority of potentially eligible subjects from those not meeting eligibility criteria.  This 
will consist of a brief discussion of the research study, confirming a potential participant’s 
understanding of the basic study procedures, interest in participation and whether he/she meets 
eligibility criteria and includes asking for current medications, gender, age, history of claustrophobia, 
pregnancy status, history of psychiatric conditions including substance use disorders. Screening 
takes place over the phone in response to a potential participant inquiry (see attached screening 
telephone script).  Those not eligible for the experiment based on the phone screen will be informed 
that they do not qualify for entry into this particular study.  An initial cohort of up to 2000 adults will be 
recruited, and 400 will be enrolled.  The research study consent form will be made available to the 
participants on their study visit before any study procedures occur.  
 
A non-identifying prescreening log will be kept for all individuals screened. The screening log will 
include a non-identifying subject ID, the date of screening, whether eligibility criteria were met, reason 
for exclusion, and enrollment decision or status.  
 
 
VII. INFORMED CONSENT 
Participants who are deemed eligible on the basis of the phone screen will be asked to come in or to 
participate in a teleconference for a study visit.  At the time of such visit, informed consent will be 
obtained by a trained member of the study staff with investigator back-up, prior to administering any 
study procedures.  All participants will be given the opportunity to ask questions to a doctoral-level 
member of study staff or an Investigator during the consent process.  Contact information of key 
study staff will be provided and participants will be informed that the investigators are available to 
answer any questions or concerns they may have about the study.  All enrolled participants will be 
provided with a copy of their signed consent form. 
 
 
VIII. PARTICIPANT WITHDRAWAL 
Participation is voluntary, and participants may stop being in the study at any time or decide not to 
join the study. If a participant decides not to participate, they will not be penalized in any way, and will 
not lose any benefits to which they are otherwise entitled.  
 
 
IX. CONFIDENTIALITY 


 
11 
All phases and aspects of this project will be conducted according to the Declaration of Helsinki, and 
will comply with HIPAA regulations. The sponsors of this research will only have access to data on 
individuals that is stripped of all unique identifiers according to HIPAA guidelines.  
 
 
Biostatistical Analysis 
Data variables collected for study 
Standardized questionnaires, assessing drug use, personality characteristics, and anxiety will be 
collected. Cognitive data will be collected using standardized computer programs such as the 
CANTAB. MRI data will also be collected. 
 
Data will be collected and managed using REDCap (Research Electronic Data Capture) tools (Harris 
2009) hosted with Partners HealthCare. REDCap data collection projects rely on a thorough study-
specific data dictionary defined in an iterative self-documenting process by all members of the 
research team with planning assistance from Partners HealthCare Research Computing, Enterprise 
Research Infrastructure & Services (ERIS) group. The REDCap Survey is a powerful tool for building 
and managing online surveys. The research team can create and design surveys in a web browser 
and engage potential respondents using a variety of notification methods. Participants will complete a 
number of REDCap Surveys using a tablet provided to them at study visits. This platform allows 
access to specific surveys and participants are required to initial at the completion of each. Study staff 
members will initial to indicate who completed each item. Both REDCap and REDCap Survey 
systems provide secure, HIPAA compliant, web-based applications that are flexible enough to be 
used for a variety of types of research, provide an intuitive interface for users to enter data and have 
real time validation rules (with automated data type and range checks) at the time of entry. Online 
dosing diaries will be collected using Secure Survey, a web application designed to collect data from 
a modern user group on their mobile, tablet, or desktop devices. This platform secures not only the 
data transmission, but also the storage using industry standard security techniques.  
 
Analytic Plan  
Power/Sample Size. Aim 1 seeks to address the development of CUD (dependent on the number of 
symptoms reported) in the MM compared with the WLC group. To assess this, we will use the DSM-5 
criteria for CUD, which combines the DSM-IV categories of abuse and dependence into a single 
disorder measured on a continuum from mild to severe. We have based power sample size 
requirements on the between and within subject ANOVA of the dependent variable of CUD 
symptoms, comparing the MM versus WLC conditions tested across the baseline to 3 month periods, 
where the primary effect of interest is the condition X time interaction. A power analysis using the 
Gpower computer program29 indicated that a sample of 80 participants per group would be needed to 
detect small to medium effect (Cohen’s d=.3) with 90% power using a t test with alpha at .05.  
Data Analysis Plan: In general, 3 analytic approaches will be employed, corresponding to three 
types of comparisons and data:     
(a) Numeric Data Assessed at Baseline, 3 Months, 6 Months and 1 year.  Measures of addiction, 
tolerance, and cognitive performance will be analyzed with a between- and within-subject analysis of 
covariance, the primary between-subject factor being Condition, i.e., the active MM vs. WLC group, 
and the within-subject factor being time, i.e., assessments at baseline and 3 months. Relevant 
subject-level numeric covariates (i.e. THC metabolite levels) and categorical factors (e.g. disease 
category) crossed with condition and possibly interacting with time will be included in the analysis. 
Covariates such as baseline MJ use, primary disorder for which MM is sought, age, and gender will 
be of interest.  The term of primary interest will be the interaction of condition x time as a test of the 
hypothesis that assignment to the MM condition will be associated with an increased rate of CUD. A 
limited amount of backward elimination of nonsignificant ancillary terms will be employed to increase 
power for effects of more interest (e.g. non-significant terms can be dropped from the models).  An 
additional, analogous repeated-measure ANCOVA, restricted to the MM group, will include the third 


 
12 
assessment at 6 months. The Greenhouse-Geisser adjustment for correlated error will be employed 
for significance tests with more than one degree of freedom. For all models, residuals will be checked 
graphically for adherence to assumptions of normality and homoscedasticity, and data 
transformations applied if needed.           
(b) Daily Numeric Data Collected via Dosing Diaries in the First 3 Months.  Daily-recorded 
numeric measures such as dose and frequency of use of MJ, of analgesic, anxiolytic, and/or 
antidepressant medications, and ratings of pain, sleep, mood, and anxiety will be analyzed as 
dependent variables in separate analyses. Preliminary exploratory graphical analyses will be 
conducted using longitudinal “spaghetti plots” in order to check any need for curvilinear models, 
explore any clusters of trajectories, and address distribution problems such as floors/ceilings, non-
normality, outliers, etc.  Analysis methods employed will be mixed fixed and random effects 
longitudinal models. Fixed terms will be Condition (MM vs. WLC groups) and various relevant crossed 
factors and numeric covariates.  Correlated random terms will be subjects’ intercepts and linear rate 
of change of their trajectories on the dependent variable across days (curvilinear terms will be 
included if warranted). In order to test the predictive relation of some of the time-varying variables 
(e.g., frequency of MJ use) on others (e.g., pain recordings or use of analgesic, anxiolytic, and/or 
antidepressant medications), the former will be included as additional time-varying predictors in 
models otherwise analogous to those above.  Exploratory structural equation models (SEM) and 
cross correlations of time series will be examined for evidence of underlying causal dynamics.  Cross-
lagged partial correlations can be used to test direction of effects.     
(c) Imaging Data. Imaging data will be analyzed using standard analysis platforms for longitudinal 
analysis (e.g. FSL and SPM). We will use a linear mixed-effects model approach, with a univariate 
two-stage specification. The advantage of this method is that it offers flexibility in handling 
unbalanced repeated measurements with missing data, which is one of the biggest challenges to 
longitudinal fMRI datasets. At the subject-level, a unique trajectory for each individual is defined for 
each region or voxel being considered, meaning that activation measurements are condensed into 
summary statistics for each scan. At the second, population-level, individuals are considered as 
arising from a population of all such individuals, each with a unique intercept and slope, and a linear 
mixed-effects model is fit. With this modeling approach, it is reasonable to deduce that the within-
individual variances are the fluctuations around the individual-specific trajectory, and the among-
individual variances can be described as differences of parameters characterizing these trajectories. 
As one way to conduct this model using brain-imaging data, statistical measures of brain activity 
responses serve as the dependent variable and one linear mixed-effect model is then fit for each ROI 
or voxel. Repeatability of fMRI can be directly addressed via certain parameters of this model. 
 
 
Risks and Discomforts 
 
Psychosocial risks 
Risks: There are no legal risks to the participants associated this study, because medical marijuana is 
legal in Massachusetts.  There is a small social risk associated with participation in this study, as 
some people may be embarrassed if others found out that they are using medical marijuana. 
Minimization: All data will be completely deidentified and anonymized. Please see ‘confidentiality and 
loss of privacy’ below. 
 
The Co-Investigators on this project include a psychiatrist (Dr. Eden Evins) and a clinically-trained 
clinical psychologist (Dr. Randi Schuster).  If there are any concerns about a subject who is actively 
suicidal and in need of clinical attention, the PI will be made aware of the issue immediately and will 
consult with appropriate medical personnel (co-investigators Eden Evins and Randi Schuster) to 
determine appropriate steps. The PI and medically trained co-investigators will assess the needs of 
the subject and offer the subject either prompt treatment or medical referral, whichever is appropriate 


 
13 
for the situation. There is a licensed clinician on site 40 hours per week, and other MGH resources 
can be used as necessary. 
 
Confidentiality and Loss of Privacy 
Risks: The risk of loss of privacy is judged to be minimal. Online dosing diaries will be collected using 
Secure Survey, which secures not only the data transmission, but also the storage using industry 
standard security techniques.  
Minimization: Confidentiality will be maintained by numerically coding all data and by keeping all data 
in password protected databases. Subject information will be accessible only to research staff. 
Information about study participants will not leave our institution in any form that would identify 
individual subjects.  
Secure Survey implements multiple layers of security using industry standard techniques:  
• 
SSL Certificates from Trusted Certificate Authorities encrypts all traffic between the user’s 
device and the server 
• 
All database data is encrypted using 256-bit encryption ensuring no data is at risk should the 
servers be breached 
• 
Browser tokens further secure the flow between pages and help prevent XSS attacks 
 
fMRI Risks 
Risks: fMRI is a minimal risk procedure. Although fMRI scanning itself is painless, subjects may 
experience discomfort. Some may become claustrophobic inside the magnet. Subjects may also be 
bothered by the beeping and hammering sounds made when the scanner is collecting 
measurements, and/or experience peripheral stimulation, manifested as a gentle tap or sensation of 
mild electric shock.  Because of the high magnetic field of the fMRI scanner, individuals with 
pacemakers, cosmetics, or certain metallic implants in their bodies must be excluded. Each potential 
subject must identify these and other possible contraindications prior to fMRI scanning.  Because the 
scanner attracts certain metals, precautions must be taken to remove metallic objects from the MRI 
room. 
 
Minimization: Since some subjects may be uncomfortable in the MRI, all subjects will be able to 
converse with the experimenter via a microphone and speaker system, and will be able to 
communicate an immediate need to come out or stop the scan via a “panic squeezeball”. All efforts 
will be made to make the subjects as comfortable as possible while in the scanner. A member of the 
study staff will explain the procedure thoroughly to the subjects prior to scanning, allowing for 
maximal understanding and comfort. The MRI can be stopped at any time at the subjects’ request. In 
addition, the scanners are equipped with an emergency button that the subject can press if 
necessary. A qualified M.D. will always be on site or reachable by pager in the unlikely event that an 
adverse event occurs. If there are any concerns about a subject in need of clinical attention, the PI 
will be made aware of the issue immediately and will consult with appropriate medical personnel (co-
investigator: A. Eden Evins, MD) to determine appropriate steps.  
 
Potential subjects will be carefully screened before recruitment with respect to their medical history. 
This includes: history of head trauma, surgical aneurysm clips, cardiac pacemaker or any other type 
of implants, metal rods or plates. They will be queried about their previous surgeries, hearing aid, 
intrauterine devices, dentures and pregnancy. Individuals with any one of these contraindications will 
not be recruited for the study.  
 
If there are any concerns about a subject in need of clinical attention, the PI will be made aware of the 
issue immediately and will consult with appropriate medical personnel (co-investigator Eden Evins, 
MD) to determine appropriate steps. The PI and medically trained co-investigators will assess the 
needs of the subject and offer the subject either prompt treatment or medical referral, whichever is 


 
14 
appropriate for the situation. There is a licensed clinician on site 40 hours per week, and other MGH 
resources can be used as necessary. 
 
 
Potential Benefits 
Participants may find that talking about marijuana use increases their awareness of any issues 
related to drug use. Any participant who asks about treatment will be provided information regarding 
local drug treatment programs.  
 
Information developed from this study may help researchers in the future.  Specifically it is expected 
that this study will provide valuable information about effects and consequences of MM use, where 
few studies have been published. The proposed project will fill a critical gap in the addiction literature, 
at a critical time when cannabis is being legalized for ‘medical’ use with little known about effects of 
MM on target symptoms, addictions, neurocognition or brain structure and function.  
 
MONITORING AND QUALITY ASSURANCE 
All participants will have contact information for the principal investigator and the study coordinator if 
they have questions at any time.  Dr. Gilman is responsible for the overall management of the study 
and will maintain regular communication with all of the study staff.  The PI will meet weekly with all 
study investigators to review the details of data acquisition and analysis as well as any minor 
problems.  In the event of any significant adverse event, the PI will be contacted immediately. The PI 
is responsible for the generation of summary reports to NIH documenting this process and outcome, 
which will also be included in the Continuing Review reports to the IRB. 
 
Serious adverse events are not expected as a result of the study procedures.  Should one occur, it 
will be reported by telephone or email by the principal investigator to the Partners IRB according to 
current PHRC Adverse Event Reporting Policy (version dated: March 13, 2007).  All adverse events 
(if not serious) will be reported in writing to the Partner’s Human Research Committee.  All 
information regarding experimental subjects will be kept in the offices of the Principal Investigator.  All 
data will be identified by a unique code number.   
 
 
 
 
 
References 
 
1. 
Substance Abuse and Mental Health Services Administration, Results from the 2013 National 
Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-48, HHS 
Publication No. (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services 
Administration; 2014:31. 
2. 
Substance Abuse and Mental Health Services Administration, Results from the 2013 National 
Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-48, HHS 
Publication No. (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services 
Administration; 2014:25. 
3. 
Kann LK, S.; Shanklin, S. L.; Flint, K.H.; Hawkins, J.; Harris, W.A.; Lowry, R.; O'Malley 
Olsen, E.; McManus, T.; Chyen, D.; Whittle, L.; Taylor, E.; Demissie, Z.; Brener, N.; 
Thornton, J.; Moore, J.; Zaza, S. Youth Risk Behavior Surveillance - United States, 2013. 
Rockville, MD: ICF International; Westat; 2014:20. 


 
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4. 
Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. 
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Piomelli D. The molecular logic of endocannabinoid signalling. Nature reviews. Neuroscience. 
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Martin-Santos R, Fagundo AB, Crippa JA, et al. Neuroimaging in cannabis use: a systematic 
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Solowij N, Battisti R. The chronic effects of cannabis on memory in humans: a review. 
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Solowij N, Stephens R, Roffman RA, Babor T. Does marijuana use cause long-term cognitive 
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Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 
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Anthony JC. Cannabis dependence: Its Nature, Consequences and Treatment. Cambridge, UK: 
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Lopez-Quintero C, Perez de los Cobos J, Hasin DS, et al. Probability and predictors of 
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13. 
DrugFacts: Marijuana. 2010; http://www.drugabuse.gov/publications/drugfacts/marijuana. 
14. 
Hooper SR, Woolley D, De Bellis MD. Intellectual, neurocognitive, and academic 
achievement in abstinent adolescents with cannabis use disorder. Psychopharmacology. 
2014;231(8):1467-1477. 
15. 
Ware J, Jr., Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of 
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16. 
Kessler RC, Adler L, Ames M, et al. The World Health Organization Adult ADHD Self-Report 
Scale (ASRS): a short screening scale for use in the general population. Psychological 
medicine. 2005;35(2):245-256. 
17. 
Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. 
Journal of clinical psychology. 1995;51(6):768-774. 
18. 
Weber EU, Blais, A., & Betz N.E. A Domain-specific Risk-attitude Scale: Measuring Risk 
Perceptions and Risk Behaviors. Journal of Behavioral Decision Making. 2002;15:263–290. 
19. 
The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): development, 
reliability and feasibility. Addiction. 2002;97(9):1183-1194. 
20. 
Sobell MB, Sobell LC, Klajner F, Pavan D, Basian E. The reliability of a timeline method for 
assessing normal drinker college students' recent drinking history: utility for alcohol research. 
Addictive behaviors. 1986;11(2):149-161. 
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Bohn MJ, Krahn DD, Staehler BA. Development and initial validation of a measure of 
drinking urges in abstinent alcoholics. Alcoholism, clinical and experimental research. 
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Adamson SJ, Sellman JD. A prototype screening instrument for cannabis use disorder: the 
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23. 
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol 
Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of 
Persons with Harmful Alcohol Consumption--II. Addiction. 1993;88(6):791-804. 
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Schafer J, Brown SA. Marijuana and cocaine effect expectancies and drug use patterns. 
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Farrar JT, Young JP, Jr., LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes 
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tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and 
depression symptom scales. Journal of abnormal psychology. 1995;104(1):3-14. 
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Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH. Worth the 'EEfRT'? 
The effort expenditure for rewards task as an objective measure of motivation and anhedonia. 
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2007;39(2):175-191. 
 
 

ICF_001.pdf: 
Effect of Medical Marijuana on Neurocognition and Escalation of Use 
NCT03224468
Date: 04/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 1 of 14
Subject Identification
Protocol Title: Effect of Medical Marijuana on Neurocognition and Escalation 
of Use
Principal Investigator: Jodi Gilman, Ph.D.
Site Principal Investigator:      
Description of Subject Population: Adults ages 18-65 who are interested in using 
medical marijuana for pain, sleep or mood, and/or anxiety
About this consent form
Please read this form carefully.  It tells you important information about a research study.  A 
member of our research team will also talk to you about taking part in this research study.  
People who agree to take part in research studies are called “subjects.”  This term will be used 
throughout this consent form.
Partners HealthCare System is made up of Partners hospitals, health care providers, and 
researchers.  In the rest of this consent form, we refer to the Partners system simply as 
“Partners.”
If you have any questions about the research or about this form, please ask us.  Taking part in 
this research study is up to you.  If you decide to take part in this research study, you must sign 
this form to show that you want to take part.  We will give you a signed copy of this form to 
keep.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time.
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 2 of 14
Subject Identification
Why is this research study being done?
The purpose of the study is to help us learn about peoples’ behavior once they start using 
medical marijuana (MM). We hope to better understand patterns of use of medical marijuana, as 
well as any effects of medical marijuana on cognition or on the brain, including the potential for 
marijuana dependence/addiction. 
We are asking you to take part in this research study because you have pain, sleep or mood, 
and/or anxiety disorder, but are otherwise healthy, and are thinking about obtaining a medical 
marijuana card.  
This study will not give out MM. You will have to get a prescription for MM from your own 
doctor. You and your health insurance will be responsible for the costs of MM. We can provide 
information about procedures involved with obtaining a MM card.
About 400 subjects will take part in this research study.
The National Institute on Drug Abuse is paying for this study to be done.
How long will I take part in this research study?
This study consists of seven visits to MGH that will last approximately 2-3 hours, over the 
course of 12 months. During the visits, you will participate in interviews, fill out questionnaires, 
and perform some tests on a computer.  Some people will also have the option to have an MRI 
scan. 
What will happen in this research study?
If you choose to take part in this study, we will ask you to sign this consent form before we do 
any study procedures. We will also ask for your permission to send text message reminders to 
your phone to confirm your study visits.
Visit 1: Screening Visit
The Screening Visit will take about two to three hours to complete. At this visit, we will:

Ask you for a urine sample.

Test your urine for certain drugs, including illegal drugs such as cocaine and marijuana. 
If your urine shows you have taken any illegal drugs (except for marijuana), you can't be 
in this study. The results of the urine drug test will not become part of your medical 
record. These test results will, however, remain part of your confidential study record. 
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 3 of 14
Subject Identification

Test your urine for pregnancy, if you are a female able to become pregnant. (People who 
are pregnant or are planning to become pregnant in the next year can't take part in this 
research study).

Ask you to fill out some questionnaires about your general medical/psychiatric health, 
substance use and symptoms. 

Assess your eligibility and randomize you to either the active study group or the control 
group.

If you are assigned to the active study group and choose to take part in the MRI scanning 
portion of this study, this procedure will be scheduled shortly after this screening visit.
Assignment to study group
If after the screening visit, you qualify to take part in this study, we will assign you by chance to 
the MM group or the control group.  You and the study doctor cannot choose your study group. 
We use control groups in research studies to learn if the effects seen in research subjects are truly 
from a particular treatment. 
If you are assigned to the active study group, you will have the option of getting MM card any 
time. We will also ask you to start keeping track of your marijuana use via an online web 
platform called Secure Survey starting after the Screening Visit. Additionally, we will call you 
approximately two weeks after your screening visit to follow up on the status of your medical 
marijuana application. We will also call you approximately four weeks after and six weeks after 
the screening visit if you have not made progress on your application. If after six weeks, you still 
have not made any progress on your application for a medical marijuana card (i.e., made an 
appointment with a doctor who recommends medical marijuana), we will schedule a three month 
follow-up visit, which will be your final study visit. Once you get your MM card, we will then 
schedule more visits at baseline and approximately 2 weeks, 4 weeks, 3 months, 6 months and 12 
months after baseline. 
If you are assigned to the control group, you will be asked to wait until you have completed your 
three-month study visit to get your medical marijuana card. We will ask you to start keeping 
track of your marijuana use via an online web platform called Secure Survey starting after the 
Screening Visit and schedule your Baseline Visit (usually within three to four weeks of your 
screening visit). During the first three months after Baseline, you will come in for additional 
study visits at approximately 2 weeks, 1 month, 3 months. After three months, you may choose 
to obtain a MM card. Afterwards, you will come in for 6-month and 12-month visits. 
The decision to wait three months, as well as the decision to obtain a MM card after 3 months, 
should be made in consultation with your prescribing physician. 
Visit 2: Baseline Visit:
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 4 of 14
Subject Identification
During this initial study visit we will ask you to:

Fill out questionnaires about your general medical/psychiatric health, substance use and 
symptoms

Answer questions about your medical and psychiatric health

Provide a urine sample to check for illegal drug use 
(This urine drug screen test result will not become part of your medical record)

Participate in cognitive testing that will evaluate your memory, attention, inhibitory 
control, and risk/reward performance
Visits 3 (2 Week), 4 (1 month), 5 (3 months), 6 (6 months): At these study visits, we will ask 
you to repeat all procedures you completed during your baseline study visit.
Visit 7 (12 month visit):
At your final study visit, you will be asked to complete the following procedures:

Fill out questionnaires about your general medical/psychiatric health, substance use and 
symptoms

Provide a urine sample to check for illegal drug use 

Participate in cognitive testing that will evaluate your memory, attention, inhibitory 
control, and risk/reward performance

Complete another MRI scan shortly after this visit, if you previously had an MRI scan 
at/near your baseline study visit. 
Monthly Phone Calls:
On months (2, 4, 5, 7-11 months after the baseline visit) when you do not have a study visit, and 
2 years after your baseline study visit, you will receive monthly phone calls from a research 
coordinator to update:

New medications or changes to existing medications

Recent substance use

Overall physical and mental health
These phone calls take about 10-15 minutes to complete and are important for updating any 
changes between study visits.
Online Dosing Diaries:
You will be asked to keep track of your marijuana use, as well as ratings of mood, sleep, and 
pain, every day via an online app called Secure Survey. You will be paid for submitting this data 
when you come in for your next study visit. 
Brain Imaging Assessments:
The MRI portion of the study will investigate possible changes in the brain from those who 
obtain medical marijuana cards. Therefore, only patients randomized into the active MM group 
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 5 of 14
Subject Identification
will be given the option to undergo MRI scanning. If you are selected to undergo MRI 
procedures and choose to participate, we will take pictures or images of your brain using a 3T 
MRI machine. These assessments will occur as close as possible to your Baseline Visit and to 
your One Year Visit, depending on your schedule and availability. These images allow us to see 
which parts of your brain are active when you move a part of your body, such as your hand or 
foot, or when you speak. The MRI test will take about 1.5 hours. Your MRI will be done at the 
MGH MRI Center in the Charlestown Navy Yard. 
An MRI uses a strong magnet and radio waves to take these pictures. Since MRI uses a large 
magnet, people who have certain metal implants cannot have this scan.  Also you will be asked 
to remove all metal items before the scan. 
During the MRI, you will lie on a table that slides into a ring-shaped machine a little wider than 
your body. It is important that your head does not move during the MRI, so we place foam 
pillows around the back and sides of your head. We will ask you not to move at all, except when 
we tell you to. During the MRI, you will hear knocking, tapping and buzzing sounds made by the 
MRI machine. You will be wearing headphones and/or earplugs so the sounds will not be too 
loud. Part of the time you will be resting. Most of the time, we will ask you to perform a 
computer task. If at any time you feel uncomfortable and want to stop the task or the MRI, please 
tell us. We will stop right away.
Do you agree to take part in the MRI portion of the study? 
  YES
 NO
Initials_________________
Urine Sample Shipments:
We will collect urine samples at every study visit, which will be tested for drugs and pregnancy 
(in females). With your permission, a small quantity (<10mL) of the urine sample will be 
shipped to collaborators at a lab who can quantify cannabinoids in the urine. We will only ship 
your sample if a) you agree to having your samples shipped, AND b) you report using marijuana 
products since your last study visit, and/or c) your qualitative urine drug test is positive for THC.
Do we have your permission to ship urine samples for quantitative analysis? 
  YES
 NO
Initials_________________
Information Storage
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 6 of 14
Subject Identification
Study information collected from you will be stored in a password-protected research database 
on a password-protected computer. This information will not become part of your medical 
record. 
We will assign all information a unique code. The key to the code will be kept on a password-
protected computer. Only the researchers from our research study will be able to use the 
computer. The code linking test results to subject identity will only be accessible to study staff.
If you decide to drop out of this research study at a later time, please contact one of the research 
coordinators for this study:
Aly Dechert: (617) 643-7611; adechert@mgh.harvard.edu
Billy Schmitt: (617) 724-0367; waschmitt@mgh.harvard.edu
Grace Wheeler: (617) 643-4692; gwheeler@mgh.harvard.edu
Rachel Plummer: (617) 724-0382; rplummer1@mgh.harvard.edu
What are the risks and possible discomforts from being in this research 
study?
Risk of MRI Scans: 
MRIs use powerful magnets to make images. There are no known radiation risks associated with 
MRI. However, persons with metal implants, such as surgical clips, or pacemakers should not 
have an MRI. All credit cards and other items with magnetic strips should also be kept out of the 
MRI room. People who feel uncomfortable in confined spaces (claustrophobia) may feel 
uncomfortable in the narrow tube. The MRI makes loud banging noises as it takes images. 
Earplugs can be used to reduce the noises. The MRI can be stopped at any time at your request. 
If you are or suspect you are pregnant, you should not participate in this study. The MRI has the 
potential, during normal routine use, to cause localized warming of your skin and the underlying 
tissues. You should immediately inform us if you experience discomfort due to warming and the 
procedure will be stopped. 
Some people experience dizziness or rarely nausea when going into an MRI scanner and these 
sensations may be more common in scans with higher magnetic fields. In most cases, these 
symptoms only last a short time. However, some people may experience them throughout the 
scan and/or continue to experience them for a short period of time after; generally, less than half 
an hour. No case of permanent problems is known.
Risk of incidental findings on the MRI
We are doing the MRI in this study to answer research questions, not to give you medical care. 
The information created by this study will not usually become part of your hospital record. This 
MRI is not the same as one that your own doctor would order. It may or may not show problems 
that would be found on a standard MRI.
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 7 of 14
Subject Identification
If we do see something that looks like a medical problem, we will ask a radiologist (a doctor who 
specializes in x-rays/scans/test results of this sort) to review the results. If the radiologist thinks 
there might be a problem, we will tell you and help you get follow-up care. If the radiologist 
thinks that you might have a medical problem, but it turns out that you don’t, we may have 
caused you to worry needlessly about your health.
Loss of confidentiality
We will not share your identity with anyone outside the Partners institutions. However, we 
cannot guarantee your confidentiality.
We will numerically code all data and remove all personal identifiers from the data. We will 
store all data in password protected databases. Subject information will be accessible only to 
research staff. Information about study participants will not leave our institution in any form that 
would identify individual subjects. 
Medical Marijuana:
The cardiovascular effects of marijuana largely depend on several factors, including dose, 
frequency, route of administration, and duration of use. THC can have diverse effects on heart 
rate and blood pressure, and although present knowledge about the relationship between 
marijuana or medical marijuana use and cardiovascular disease outcomes is still limited.
There may be other risks of medical marijuana that are not known yet.
What are the possible benefits from being in this research study?
You will not directly benefit from taking part in this research study. Others taking MM in the 
future may benefit from what we learn in this research study.
What other treatments or procedures are available for my condition?
You do not have to take part in this study to be treated for pain, sleep disorders, or mood/ 
anxiety disorders. Other treatments or procedures that are available to treat these conditions, 
which should be discussed with your doctor, include:
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 8 of 14
Subject Identification

Pain: A number of over-the-counter medications including acetaminophen, aspirin, 
ibuprofen, and naproxen. For more severe pain doctors may prescribe muscle relaxants, 
anti-anxiety drugs, antidepressants like Valium, prescription anti-inflammatory drugs like 
Celebrex, or short acting painkillers such as codeine, fentanyl, oxycodone and 
hydrocodone. In the most severe cases, steroid injections at the site of pain in the most 
severe cases may be used.

Sleep disorders: Psychotherapy and changes in sleeping habits can be effective in 
reducing symptoms depending on the type of sleeping disorder. The most commonly 
prescribed medications to treat insomnia include Ambien, Lunesta, and Rozerem. 

Mood and anxiety disorders: Psychotherapy and/or medications can be effectively used to 
treat mood and anxiety disorders. Common medications used to treat these disorders 
include Prozac, Zoloft, Paxil, Celexa and Cymbalta.
Can I still get medical care within Partners if I don’t take part in this 
research study, or if I stop taking part? 
Yes.  Your decision won’t change the medical care you get within Partners now or in the future.  
There will be no penalty, and you won’t lose any benefits you receive now or have a right to 
receive.
Taking part in this research study is up to you.  You can decide not to take part.  If you decide to 
take part now, you can change your mind and drop out later.  We will tell you if we learn new 
information that could make you change your mind about taking part in this research study.
What should I do if I want to stop taking part in the study?
If you take part in this research study, and want to drop out, you should tell us.  We will make 
sure that you stop the study safely.  We will also talk to you about follow-up care, if needed.
Also, it is possible that we will have to ask you to drop out of the study before you finish it.  If 
this happens, we will tell you why.  We will also help arrange other care for you, if needed.
Will I be paid to take part in this research study?
You will be paid following each study visit via check that will be mailed to you. You will be 
paid $20 for the screening visit, and $60 after each study visit. You will also be paid an 
additional $40 for completing the 6 month visit and an additional $60 for completing the 12 
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 9 of 14
Subject Identification
month visit. You will be paid an additional $10 for completing two questionnaires related to the 
Covid-19 pandemic. You will be paid $20 each week if you complete the online dosing diary 
($2/day, with a $6 bonus for completing the whole week). If you choose to participate in the 
brain scanning sessions, you will be paid $50 for each brain scan. Additionally, they may be paid 
for pre-baseline daily diary entries for a maximum of five weeks ($20 per week, $100 total). If 
you come to all study visits, complete all surveys, and complete all diaries, you will be paid a 
total of $820. If you come to all study visits, complete all surveys, complete all diaries, AND 
participate in brain scans, you will be paid a total of $920. If you undergo the screening but do 
not participate in the study, you will be paid for the screening only ($20). Please see the table 
below for a description of all payments. In accordance with Partners Policy, to receive 
payment each participant is asked to provide us their Social Security Number or Tax ID 
number. All payments will be made via check following each study visit.
Visit #
Active Study Group
Waitlist Control Group
1
Screening
$20
Screening
$20
2
Baseline
$60
Baseline
$60
3
2 weeks
$60
2 weeks
$60
4
1 month
$60
1 month
$60
5
3 months
$60
3 months
$60
Dosing Diaries
(13 weeks x $20/week)
$260
Dosing Diaries
(13 weeks x $20/week)
$260
6
6 months
$100
6 months
$100
Monthly phone calls 2, 4, 7-11 
months (7 x $10 each)
$70
Monthly phone calls 2, 4, 7-11 
months (7 x $10 each)
$70
Covid19 Questionnaires
$10
Covid19 Questionnaires
$10
12
12 months
$120
12 months
$120
Total
$820
Total
$820
Scan 
(Optional)
Baseline
$50
12 months
$50
Total
$910
What will I have to pay for if I take part in this research study?
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 10 of 14
Subject Identification
There is no cost to you for taking part in this study. The cost of all of the tests and procedures done 
for research will be paid for by study funds.
You/your health insurer will be responsible for the cost of the MM because this would be needed 
for your care even if you are not in the study.
Charges for any ongoing or routine medical care you receive outside this study will be billed to 
you or to your insurance company in the usual way.  You will be responsible for any deductibles 
or co-payments required by your insurer for your routine medical care.
What happens if I am injured as a result of taking part in this research 
study?
We will offer you the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill your insurance company or other third parties, if 
appropriate, for the care you get for the injury.  We will try to have these costs paid for, but you 
may be responsible for some of them.  For example, if the care is billed to your insurer, you will 
be responsible for payment of any deductibles and co-payments required by your insurer.
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay 
you or give you other compensation for an injury, should one occur.  However, you are not 
giving up any of your legal rights by signing this form.
If you think you have been injured or have experienced a medical problem as a result of taking 
part in this research study, tell the person in charge of this study as soon as possible.  The 
researcher's name and phone number are listed in the next section of this consent form.
If I have questions or concerns about this research study, whom can I 
call?
You can call us with your questions or concerns.  Our telephone numbers are listed below.  Ask 
questions as often as you want.  
Jodi Gilman, PhD, is the person in charge of this research study.  You can call her at 617-643-
7293 Monday through Friday 9AM to 5PM with questions about this research study. 
If you have questions about the scheduling of appointments or study visits, please contact one of 
the research coordinators for this study:
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 11 of 14
Subject Identification
Aly Dechert: (617) 643-7611; adechert@mgh.harvard.edu
Billy Schmitt: (617) 724-0367; waschmitt@mgh.harvard.edu
Grace Wheeler: (617) 643-4692; gwheeler@mgh.harvard.edu
Rachel Plummer: (617) 724-0382; rplummer1@mgh.harvard.edu
If you want to speak with someone not directly involved in this research study, please contact 
the Partners Human Research Committee office.  You can call them at 857-282-1900.
You can talk to them about:

Your rights as a research subject

Your concerns about the research

A complaint about the research
Also, if you feel pressured to take part in this research study, or to continue with it, they want to 
know and can help.
If I take part in this research study, how will you protect my privacy?
During this research, identifiable information about your health will be collected.  In the rest of 
this section, we refer to this information simply as “health information.”  In general, under 
federal law, health information is private.  However, there are exceptions to this rule, and you 
should know who may be able to see, use, and share your health information for research and 
why they may need to do so.   
In this study, we may collect health information about you from:

Past, present, and future medical records

Research procedures, including research office visits, tests, interviews, and 
questionnaires
Who may see, use, and share your identifiable health information and why they may 
need to do so:

Partners research staff involved in this study

The sponsor(s) of this study, and the people or groups it hires to help perform this 
research

Other researchers and medical centers that are part of this study and their ethics boards

A group that oversees the data (study information) and safety of this research
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 12 of 14
Subject Identification

Non-research staff within Partners who need this information to do their jobs (such as for 
treatment, payment (billing), or health care operations)

The Partners ethics board that oversees the research and the Partners research quality 
improvement programs.

People from organizations that provide independent accreditation and oversight of 
hospitals and research

People or groups that we hire to do work for us, such as data storage companies, insurers, 
and lawyers

Federal and state agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health, and other US or foreign 
government bodies that oversee or review research) 

Public health and safety authorities (for example, if we learn information that could mean 
harm to you or others, we may need to report this, as required by law)

Other:  
Some people or groups who get your health information might not have to follow the same 
privacy rules that we follow and might use or share your health information without your 
permission in ways that are not described in this form.  For example, we understand that the 
sponsor of this study may use your health information to perform additional research on various 
products or conditions, to obtain regulatory approval of its products, to propose new products, 
and to oversee and improve its products’ performance.  We share your health information only 
when we must, and we ask anyone who receives it from us to take measures to protect your 
privacy.  The sponsor has agreed that it will not contact you without your permission and will not 
use or share your information for any mailing or marketing list.  However, once your information 
is shared outside Partners, we cannot control all the ways that others use or share it and cannot 
promise that it will remain private.
Because research is an ongoing process, we cannot give you an exact date when we will either 
destroy or stop using or sharing your health information.
The results of this research study may be published in a medical book or journal, or used to teach 
others.  However, your name or other identifying information will not be used for these purposes 
without your specific permission.
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 13 of 14
Subject Identification
Your Privacy Rights
You have the right not to sign this form that allows us to use and share your health information 
for research; however, if you don’t sign it, you can’t take part in this research study.   
You have the right to withdraw your permission for us to use or share your health information 
for this research study.  If you want to withdraw your permission, you must notify the person in 
charge of this research study in writing.  Once permission is withdrawn, you cannot continue to 
take part in the study.
If you withdraw your permission, we will not be able to take back information that has already 
been used or shared with others.
You have the right to see and get a copy of your health information that is used or shared for 
treatment or for payment.  To ask for this information, please contact the person in charge of this 
research study.  You may only get such information after the research is finished. 
Informed Consent and Authorization
Statement of Person Giving Informed Consent and Authorization

I have read this consent form.

This research study has been explained to me, including risks and possible benefits (if 
any), other possible treatments or procedures, and other important things about the study.

I have had the opportunity to ask questions.

I understand the information given to me.
Signature of Subject:
I give my consent to take part in this research study and agree to allow my health information to 
be used and shared as described above.
Subject
Date
Time
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020


Partners HealthCare System
Research Consent Form
General Template
Version Date:  August 2016
Page 14 of 14
Subject Identification
Signature of Study Doctor or Person Obtaining Consent:
Statement of Study Doctor or Person Obtaining Consent

I have explained the research to the study subject.

I have answered all questions about this research study to the best of my ability.
Study Doctor or Person Obtaining Consent
Date
Time
Consent Form Version:  04/15/2020
Consent Form Title: MM_Consent_CLEAN_4.15.20
IRB Protocol No: 2015P001600
Sponsor Protocol No: v 04.15.2020
Consent Form Valid Date: 4/23/2020
IRB Amendment No: AME76
Sponsor Amendment No: N/A
Consent Form Expiration Date: 8/8/2020
IRB Amendment Approval Date: 4/22/2020