Conditions: Intoxication Alcohol Intoxication THC Intoxication Combined Alcohol THC
Keywords: fNIRS THC Intoxication
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 316
Healthy volunteers: yes

Brief summary:
This study will assess effects of tetrahydrocannabinol (THC) and THC + alcohol in marijuana users on prefrontal brain activity, using functional near-infrared spectroscopy (fNIRS) during resting state and during memory task performance. Participants will complete fNIRS testing 120 minutes following THC or identical placebo (Phase 2A), or THC/ethanol, THC/placebo ethanol, placebo THC/ethanol, and placebo THC/placebo ethanol (Phase 2B), and oxygenated hemoglobin (HbO) concentration will be measured.

Detailed description:
This study will assess the effects of THC intoxication using dronabinol (synthetic THC) on the oxyhemoglobin (HbO) signal during resting state and task-based activation in the prefrontal cortex (PFC) and resting state connectivity, as well as on neurocognitive task performance and correlations between these measurements and clinical signs of intoxication. Participants will be 150 adults who use marijuana at least monthly (aged 18-55) will be recruited to participate in this study. Participants will be given up to 80 mg of dronabinol, an FDA-approved synthetic form of THC that is used to treat loss of appetite that causes weight loss in people with AIDS. THC is the principle psychoactive drug in marijuana. The study will be conducted in regular cannabis users who present at their first study visit with a positive urine screen for THC metabolites.

Phase 2A. Investigate the effect of THC on fNIRS brain signature and its association with self-reported intoxication, laboratory measures of impairment, and the gold-standard behavioral field test of driving impairment used by law enforcement, the primary classifier.

Phase 2B. Examine potential interaction following co-administration of THC with oral ethanol exposure in healthy volunteers. Phase II is a randomized, double-blind, placebo-controlled, 2 by 2 crossover study of effect of dronabinol, ethanol, and combined dronabinol and ethanol on brain activation and connectivity as measured by fNIRS.

Arms:
arm 1: In a double-blind placebo-controlled, random order cross-over study of single dose dronabinol, participants received dronabinol or identical placebo on two separate study visits in randomized order. arm 2: In a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration, participants were randomly assigned to 1 of 4 sequences and received each of the following treatments: placebo dronabinol + placebo ethanol, placebo dronabinol + ethanol, dronabinol + placebo ethanol, \& dronabinol + ethanol.

Interventions: intervention 1: Dronabinol intervention 2: Ethanol intervention 3: Placebo dronabinol intervention 4: Placebo ethanol
Intervention descriptions: intervention 1: Dronabinol at physician determined doses of 10-80mg designed to produce intoxication. intervention 2: Oral Ethanol, dosed to obtain a breath alcohol concentration (BrAC) of approximately 0.05 BrAC (equal to 1-2 standard drinks). intervention 3: Identical in appearance to active dronabinol (overencapsulation of both active and placebo dronabinol) intervention 4: Placebo ethanol will consist of diet soda used in the active ethanol condition with 0.25ml ethanol floated on top to provide the odor of ethanol and blind the study drug.

Protocol document:
Prot_002.pdf: 
 
1 
Title: Using Imaging to Assess Effects of THC on Brain Activity 
Document Date: 3.2.20 
NCT03655717 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 2 
PARTNERS HUMAN RESEARCH COMMITTEE 
 
 
DETAILED PROTOCOL: Using Imaging to Assess Effects of THC on Brain Activity 
Protocol #: 2015P001516  
Principal Investigator: 
Jodi Gilman, Ph.D. 
Co-Investigator: A. Eden Evins, MD 
 
Version Date: 3/3/2020 
 
 
 
I. BACKGROUND AND SIGNIFICANCE 
Marijuana has become the most popular illicit drug in the western world (Substance 
Abuse and Mental Health Services Administration, 2004).  Both acute and chronic 
exposure to cannabis is associated with changes in brain activity in frontal, limbic and 
also cerebellar regions, with generally increased brain activity following acute exposure 
and generally decreased activity during abstinence (Quickfall, 2006). Regions showing 
differences in brain activity involve the extended dopamine reward pathways and the 
frontocerebellar network.  
 
Most brain imaging studies of acute marijuana exposure have demonstrated global 
cortical activity increases during administration of smoked cannabis or infused THC. 
Several techniques have been used to track alterations of the brain associated with 
marijuana intoxication (Mathew and Wilson, 1992, Levin, 2001 and Mathew et al., 
1997). Using positron emission tomography (PET), studies have shown that marijuana 
intoxication is associated with global and rCBF increases that are most notable over the 
frontal regions and, in right-handed subjects, in the right hemisphere, (Mathew et al., 
1997). Ratings of intoxication and euphoria correlated with the right hemispheric rCBF 
increase (Mathew et al., 1997). In another PET study, Volkow et al. (1991a) showed 
that increased cerebellar metabolism while intoxicated correlated with intoxication and 
plasma THC levels. In another report (Volkow et al.,1991b). FMRI studies have also 
shown increases in brain regions when individuals are intoxicated.  In two 
pharmacological fMRI studies, Bossong and colleagues investigated the acute effects of 
THC, administered with a Volcano vaporizer (6 mg), and found that activity during a 
memory task was significantly increased in a network of memory-related brain regions, 
particularly when workload increased.  
 
PET and FMRI both have limited ability be used in real-world settings. An alternative 
technology that has not been used to assess the effects of THC on brain function is 
functional near-infrared spectroscopy (fNIRS). fNIRS is a neuroimaging technology for 
mapping the functioning human cortex that exploits the principles of near-infrared 
spectroscopy (NIRS). An fNIRS headset can be quickly fixed to the forehead and 
enables measurements of the prefrontal cortex (PFC) within minutes, while 
guaranteeing high data quality. NIRS is based on the fact that: 1) human tissues are 
relatively transparent to light in the NIR spectral window (650–1000 nm); 2) NIR light is 
either absorbed by pigmented compounds (chromophores) or scattered in tissues; 3) 
NIR light is able to penetrate human tissues (Delpy and Cope, 1997); and 4) the 


 
3 
relatively high attenuation of NIR light in tissue is due to the main chromophore, 
hemoglobin (the oxygen transport red blood cell protein), located in small vessels of the 
microcirculation, such as capillary, arteriolar and venular beds. NIRS is weakly sensitive 
to blood vessels >1 mm because they completely absorb the light. The absorption 
spectrum of hemoglobin depends on its level of oxygenation. NIRS is a non-invasive, 
safe technique that utilizes 1) laser diode and/or light emitting diode light sources 
spanning the optical window between 650 and 1000 nm, and 2) flexible fiber optics to 
carry the NIR light to (source) and from (detector) tissues. Fiber optics are suitable for 
any head position and posture. Adequate depth of NIR light penetration (almost one half 
of the source-detector distance) can be achieved using a source-detector distance 
around 3 cm. So far, fNIRS has been promoted in a number of fields in which functional 
magnetic resonance imaging (fMRI) is limited due to the constraints induced by the 
scanning environment. These devices can be utilized, for example, in infant and 
children developmental studies, in neurorehabilitation assessment, and in simultaneous 
brain activation studies on multiple subjects. Finally, the fNIRS field is continuing to 
grow as more researchers from diverse fields engage the technology. In the current 
study, we will use fNIRS to assess the effects of THC intoxication on the prefrontal 
cortex.  
 
Dronabinol (marinol) is an FDA approved, synthetic, orally active cannabinoid that has 
been shown to be effective for appetite stimulation and safe for chronic use at doses up 
to 210 mg per day, although after dosing of 210 mg per day for 16 days a withdrawal 
syndrome was described with abrupt discontinuation. Doses of 2.5-20 mg per day are 
used for appetite stimulation and antiemetic indications. Doses of 0.5 mg/kg body 
weight reliably produce intoxication (easy laughing, elation and subjective heightened 
awareness)  
 
II. SPECIFIC AIMS 
Aim 1. Assess the effects of THC intoxication using the medication dronabinol 
(synthetic THC) on resting state and task-based activation in the prefrontal cortex 
(PFC), as well as on neurocognitive task performance and correlations between these 
measurements and clinical signs of intoxication.  
 
Aim 2. Investigate at which doses of dronabinol an effect on neurocognitive task 
performance or an effect on PFC activity can be observed.  
 
Aim 3. Examine potential interaction following co-administration of THC with oral 
ethanol exposure in healthy volunteers. 
 
Before enrolling patients in the dronabinol trial, we will enroll 20 participants in Phase 0, 
in order to pilot the cognitive tasks in order to determine which tasks optimally activate 
the PFC. In Phase 0, participants will undergo one hour-long fNIRS testing session 
without taking a dronabinol capsule. Inclusion criteria will be identical to Phase 1, Phase 


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2 and Phase 3, EXCEPT that participants will not be required to be regular marijuana 
users.  
 
  
III. PARTICIPANT SELECTION 
Inclusion Criteria 
General (Phase 2A, 2B 3) 
1. Men and women aged 18-55 years, inclusive; (for Phase 2B: men and women aged 
21-55 years, inclusive) 
2. Competent and willing to provide written informed consent;  
3. Able to communicate in English language.  
4. Regular, at least monthly, marijuana use, confirmed by positive urine screen for THC 
 
Additional Inclusion Criteria For Phase 2B: 
5. Past consumption of at least two alcoholic beverages in one occasion. 
6. Past co-consumption of alcohol and THC at least once in lifetime with no serious 
adverse effects. 
7. Weigh more than 100 lbs. 
 
Exclusion Criteria: 
General (Phase 2A, 2B 3) 
1. Any unstable, serious medical illness, or cardiovascular disease or events. 
2. New or unstable psychiatric symptoms, schizophrenia, or bipolar I disorder,  
3. Diabetes, cirrhosis, renal failure, Hepatitis C, HIV, 
4. History of syncope without an identified situational stressor, migraines >1x/month, 
head injury with prolonged unconsciousness (> 24 hours); 
5. Allergy to sesame oil (contained in Marinol pills) or Marinol capsules 
6. Daily use of benzodiazepines or barbiturates, antihistamines, atropine, scopolamine, 
or other strong anticholinergic agents; 
7. Current pregnancy or lactation, or trying to become pregnant (confirmed by urine 
pregnancy test) 
6. In the opinion of the investigator, not able to safely participate in this study.  
 
Additional Exclusion Criteria For Phase 2B: 
5. Currently seeking treatment, in treatment, or in recovery from an alcohol use 
disorder. 
Tachyphylaxis and tolerance develop to the sympathomimetic effects of dronabinol and 
other cannabinoids with chronic use, suggesting an indirect effect on sympathetic 
neurons. Because inclusion criteria require regular cannabis use, and positive THC 
consistent with cannabis use in the past 3 weeks, we expect participants to have 
tolerance to the cardiovascular and subjective adverse CNS effects of dronabinol. 
Nevertheless, we will exclude potential participants with clinically significant 
cardiovascular disease.  
 


 
5 
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. 
 
In accordance with NIH guidelines, efforts will be made to attain a mix of final study 
participants, in terms of sex 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. Specifically we anticipate that half of our participants 
will be male and the other half female and that we will have representation from Asian 
American, African American and Hispanic minority groups in our final cohorts. 
 
V. REMUNERATION 
Phase I: Participants will be paid by check at the completion of the study. Participants 
will be compensated $10 per hour spent at each visit and will earn an additional $30 for 
completion of the second fNIRS session per study visit. Each study visit will take 
approximately 7 hours to complete. $100 is the maximum amount a participant can 
receive per study visit. Participants will be asked to take public transport or be dropped 
off to the study visit and a member of our study staff will: (1) arrange car service (e.g. 
Lyft) that has an approved partnership with MGH, and (2) will escort the participant to 
the cab at the end of the study visit. Alternatively, it would be acceptable for participants 
to arrange travel home with a family member or friend. If they choose to do this, a study 
staff member will ensure that someone is there to bring them home prior to departure. 
An additional $30 will be paid to participants that come in on short notice (in case of any 
last-minute cancellations). 
 
Phase IIA: Participants will attend a screening visit and 2 study visits, which require 
approximately 7-hours of testing. The screening visit will take approximately 3 hours to 
complete, and participants will be compensated $25. The Visit 1 study visit will be 
reimbursed at $100 and the Visit 2 study visit will be reimbursed at $100. Subjects will 
be paid at an hourly rate of $10 per hour if they decide to drop out of the study.  
 
Phase IIB: For Phase IIB, participants will attend a screening visit and 4 study visits, 
which require approximately 7-hours of testing. The screening visit will take 
approximately 4 hours to complete, and participants will be compensated $25. The 4 
study visits will be reimbursed at $100 per visit plus a $50 bonus at the end for study 
completion. If participants complete all five study visits, they will receive a total of $475 
in the form of a check. 
 
Phase III: Participants will be compensated $10 per hour spent at each visit and will 
earn an additional $30 for completion of the second fNIRS session per study visit. Each 
study visit will take approximately 7 hours to complete. $100 is the maximum amount a 
participant can receive per study visit. Participants will attend 3 study sessions, which 


 6 
require approximately 7-hours of testing. If participants complete all three study visits, 
they will receive a total of $300 in the form of a check. 
 
VI. PARTICIPANT ENROLLMENT 
MGH Center for Addiction Medicine study staff will conduct telephone screening of 
approximately 2000 potential subjects. A telephone screening will distinguish the 
majority of likely eligible subjects from those not likely to meet eligibility criteria.  This will 
consist of a brief discussion of the research study, confirming a potential participant’s 
interest in participation and whether he/she meets eligibility criteria and includes asking 
about cannabis use, current medications, sex, age, pregnancy status, and 
psychiatric/medical conditions. Screening takes place over the phone in response to a 
potential participant inquiry (see attached screening telephone script).  Those who are 
not eligible for the experiment based on the phone screen will be informed that they do 
not qualify for entry into this particular study. The research study consent form will be 
made available to the participants on their study visit before any study procedures 
occur. Participants who give permission to receive text messages from the study staff 
will receive appointment reminders via text through Apptoto three, two, and 1 day(s) 
before upcoming appointments. 
 
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, and enrollment decision or status.  
 
VII. INFORMED CONSENT 
Participants who are deemed potentially eligible on the basis of the phone screen will be 
asked to come in for a study visit.  At the time of such visit, informed consent will be 
obtained by a licensed physician investigator or non-physician investigator with 
physician back-up prior to administering any study procedures. All participants will be 
given the opportunity to ask questions to a physician Investigator (Dr. Eden Evins, or 
another study physician), and this will be recorded in research records.  Contact 
information of key study staff will be provided and participants will be informed that the 
co-investigators are available to answer any questions or concerns they may have 
about the study.  All eligible 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 
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.  


 
7 
 
 
X. STUDY PROCEDURES 
 
Phase 0. Pilot a number of cognitive tasks using fNIRS, in order to determine which 
neurocognitive tasks produce reliable activation of the prefrontal cortex (PFC). 20 adults 
(age 18-55) will be recruited to participate in this phase of the study. These participants 
are not required to have used marijuana, since they are not receiving dronabinol 
capsules. 
 
Phase 1. Assess the effects of THC intoxication using the medication Marinol (synthetic 
THC) on resting state and task-based activation in the prefrontal cortex (PFC), as well 
as on task performance, using a number of computerized neurocognitive tasks.  
 
Participants: 100 adults (age 18-55) will be recruited to participate in this phase of the 
study. Approximately half will be occasional marijuana users (use marijuana at least 
monthly but not more than weekly), and half will be heavy marijuana users (use 
marijuana more than once per week).  Subjects will be asked to refrain from using 
marijuana within 24 hours of the study. Since THCCOOH, the main secondary 
metabolite of tetrahydrocannabinol (THC), can be detected in urine several weeks after 
last use, we will ensure that no participant exhibits overt signs of intoxication (e.g. 
congestion of the conjunctival blood vessels (red eyes), slowed speech response, 
giddiness).  
 
 
Measures: Please see table below for questionnaires: 
 
Measures 
Baseline Questionnaires 
Frequency of substance use 
WHO ASSIST1 
Harmful alcohol use  
AUDIT2 
Alcohol consumption urge  
AUQ3 
Estimate of alcohol/marijuana use 
Timeline follow-back4 
Expectancy of marijuana effects  
MEEQ,5 
Marijuana use severity  
CUDIT6 
Marijuana craving  
State/Trait Anxiety Index 
Hospital Anxiety and Depression Scale 
Insomnia symptoms 
Cannabis withdrawal 
Consonant Trigrams Test 
Divided Attention Task 
Modified AUQ 3 
STAI 
HADS 
PSQI 
CWS 
CTT 
DAT 
Repeated Assessments During Protocol 
Drug Effects Questionnaire 
Biphasic Alcohol Effects Scale (modified) 
DEQ 
BAES 
*All questionnaires will be filled out by participants on study laptops. 
 


 8 
Cognitive Tasks during FNIRS testing: We propose to investigate neural activity 
during various attention, decision-making, language, sensory, affective or emotional 
processing tasks, as prompted by established task paradigms that have been validated 
and published under IRB approval from Partner’s scientists, or IRBs at other institutions. 
For the first 6 minutes of each fNIRS scan, participants close their eyes and rest. For 
the next 6 minutes of each fNIRS scan, participants complete the 0-back and the 2-back 
condition of the letter N-back working memory (WM) task. During the 0-back condition, 
participants are instructed to press a response button whenever a letter “X” appeared 
on the screen. For the 2-back condition, participants are instructed to press the button 
whenever the presented letter was identical to the letter presented two trials prior. 
Starting with the 2-back, blocks alternate between the 2-back and 0-back, in which 
instructions on the screen indicated whether participants should press for the 0-back or 
2-back target. Stimuli are generated, and responses were collected using PsychoPy 
(Psychophysics Software in Python).  
 
Since the fNIRS device meets the criteria for a nonsignificant risk device, we will comply 
with the abbreviated IDE requirements under §812.2 (b): 
I. 
Labeling - The device will be labeled in accordance with the labeling provisions of 
the IDE regulations (§812.5) and will bear the statement "CAUTION - Investigational 
Device. Limited by Federal (or United States) law to investigational use."; 
II. 
IRB Approval – we will obtain and maintain Investigational Review Board (IRB) 
approval throughout the investigation as a nonsignificant risk device study;  
III. 
Informed Consent – we will obtain and document informed consent from each 
subject according to 21 CFR 50, Protection of Human Subjects,  
IV. Monitoring - All investigations will be properly monitored to protect the human 
subjects and assure compliance with approved protocols (§812.46).  
V. 
Records and Reports – We will maintain specific records and make certain 
reports as required by the IDE regulations. 
Reports: 
A. 
Unanticipated Adverse Device Effects: we will submit to the sponsor and 
the reviewing IRB a report of any unanticipated adverse device effect as soon as 
possible but no later than 5 working days / 7 calendar days after the investigator first 
learns of the effect. 
B. 
Withdrawal of IRB Approval: we will report to the sponsor a withdrawal of 
approval of the reviewing IRB within 5 working days. 
C. 
Progress Reports: we will submit progress reports to the sponsor, the 
monitor, and the reviewing IRB at regular intervals but no less than on a yearly basis. 
D. 
Deviations from the Investigational Plan: we will notify the sponsor and the 
reviewing IRB of any deviation from the investigational plan to protect the life or 
physical well-being of a subject in an emergency. The notice must be provided as 
soon as possible but no later than 5 working days after the emergency occurred. If it is 
not an emergency, prior approval from the sponsor is required for changes in or 
deviations from the investigational plan. If the change or deviation may affect the 
scientific soundness of the investigational plan or the rights, safety or welfare of the 
subject, the sponsor is required to obtain prior IRB approval and also to obtain FDA 
approval for a significant risk device investigation by submitting an IDE supplement. 


 
9 
1. 
Informed Consent: If the device is used without obtaining informed 
consent, we will report this to the sponsor and to the reviewing IRB within 5 working 
days after the use occurs. 
2. 
Final Report: we will submit a final report to the sponsor and to the 
reviewing IRB within 3 months after termination or completion of the investigation. 
3. 
Other Reports: We will provide accurate, complete, and current 
information about any aspect of the investigation upon request from the reviewing IRB 
or FDA. 
Records: The following records will be maintained in one location and available for FDA 
inspection under §812.2(b): 
• the name and intended use of the device 
• the objectives of the investigation 
• a brief explanation of why the device is not a significant risk device 
• the name and address of each investigator 
• the name and address of each IRB 
• a statement of the extent to which the good manufacturing practices (21 CFR 820) 
will be followed in manufacturing the device 
 
 
Study Drug and Dosing: Participants will be given up to 50mg of MARINOL® 
(dronabinol) in all phases except Phase IIA and IIB, in which they will be given up to 
80mg of dronabinol. Dronabinol is an FDA-approved synthetic form of cannabis that is 
used to treat loss of appetite that causes weight loss in people with AIDS. Dronabinol 
contains synthetic THC, the principle psychoactive drug in marijuana. The study 
physician/nurse and co-investigator, Dr. A. Eden Evins MD, as well as physicians/nurse 
on study staff at the Center for Addiction Medicine, will be responsible for administering 
the drug. 
 
Dronabinol will be dosed at up to 80mg. The rationale for this dose is based on several 
factors. The study will be conducted in regular cannabis users who present at their first 
study visit with a positive urine screen for THC metabolites. Chronic cannabis use is 
associated with significant tachyphylaxis and tolerance to pharmacologic effects of THC 
and other cannabinoids. In healthy males who received 210 mg/day dronabinol for 16 
days, tolerance developed to the CNS effects of dronabinol (including the euphoric 
‘high’ effect) within 12 days. At doses of 5 mg/day for appetite stimulation in 139 
patients, only 18% experienced ay CNS effect (feeling high, dizziness, confusion, 
somnolence). These CNS effects are the target symptoms we wish to assess in study 
participants. Because of tolerance, the rate of CNS effects is expected to be lower in 
our study population than in non-cannabis users who participated in marinol studies for 
anti-emetic and appetite stimulation indications.  
 
Marinol was evaluated in 454 patients with cancer at doses up to 40 mg/day. At doses 
greater than 0.175 mg/kg approximately 58% reported feeling ‘high’.  The starting 
recommended antiemetic dose is 15-20mg/day, noting that dosage may be escalated 
during a chemotherapy cycle or at subsequent cycles based upon initial results. 
 


 10 
For appetite stimulation, the recommended dose range is up to 20 mg/day, and at this 
dose approximately half of patients tested have reported CNS symptoms targeted in this 
study (feeling high, dizziness, confusion, somnolence). 
 
Thus, we will dose at up to 80mg and will assess for CNS symptoms frequently during 
the study visit. The exact dronabinol dose will be clinically determined by a study 
physician. The dose will be designed to minimize adverse psychologic and physiologic 
effects of dronabinol and will be primarily based on the degree of tolerance expected 
(based on dose and frequency of cannabis use), self report of degree of intoxication 
experienced with each use, and any regular or prior negative psychological reactions to 
cannabis use or binges. This is an inexact determination as potency of cannabis used is 
almost never known. Other factors that will be considered when determining dose are 
height, weight, BMI, and baseline blood pressure. For example: Heavy daily cannabis 
users will generally receive 80mg. Daily cannabis users who use 1/2-1 gram per day 
and who weigh over approximately 140 pounds will generally receive 50mg, while those 
who use less than half a gram per day, use less than daily or who weigh less than 100 
pounds will receive between 30 and 45 mg based on the physician’s best judgment.  
 
 
Urine Drug Screen: Before study procedures are initiated, we will perform a qualitative 
urine drug screen (Multi Drug 6 Panel Urine Test; Medimpex United Inc., Bensalem, PA) 
that will test for marijuana, amphetamines, methamphetamines, cocaine, and opiates. 
These rapid tests are simple, can be done at home, and are CLIA-waived. The test will 
be administered by a trained research coordinator. 
 
Urine Pregnancy: Before study procedures are initiated, we will perform a qualitative 
urine pregnancy test for females. The test will be administered by a trained research 
coordinator. 
 
 
Overview of Procedures for Each Phase: 
 
Phase 0:  Participants will come to the MGH Martinos Center the day of their study visit. 
They will meet with a study doctor and sign the consent form. Those who are eligible 
after the telephone screen will then undergo one fNIRS testing session. The testing 
session will take approximately one hour to complete. The testing procedure only 
consists of the n-back task (see “Cognitive Tasks during FNIRS testing” for description 
of the task). There is no drug administration in Phase 0. 
 
Phase 1: Participants will come to the MGH Martinos Center the morning of their study 
day. They will meet with a study doctor, sign the consent form, and complete screening 
for eligibility. Screening consists of a substance use history interview (timeline follow 
back), medical history interview, and a urine drug and pregnancy test. Those who are 
eligible will then complete baseline questionnaires, including the DEQ and BAES. 
Participants will be trained to become familiarized with fNIRS tasks and undergo the first 
fNIRS testing session. They will then be given a dose of dronabinol. Every 20 minutes, 


 
11 
they will complete the DEQ and BAES. fNIRS testing will be repeated at 100 min (thus 
the second fNIRS session will occur over 60 minutes comprising the timespan of 90-150 
minutes after ingesting dronabinol, which is the median peak of pharmacokinetic 
effects). Participants will then have a one-hour break and undergo an optional third 
fNIRS testing session at 210-270 min (3.5-4.5 hrs after ingesting dronabinol, when 
expected effects have dissipated and the person is no longer clinically intoxicated) if 
time allows. Although not expected, if repeat fNIRS results at 210 min are consistent 
with continued intoxication, in order to obtain measurements following clinical 
intoxication, we may repeat the fNIRS testing at 330 minutes, 1.5 hours outside the 
peak window of intoxication). 
 
The fNIRS device will only be operated by individuals who have received laser use 
training: Dr. Jodi Gilman, Rachel Plummer, Olivia Downer, Audrey Steely, Rachel 
Marcus, and Nathaniel Phillips. 
See below for schematic:  
 
 
 
 
 
 
 
 
 
 
 
In between testing sessions, participants will be allowed to read, use a laptop, or watch 
movies. They will be provided with snacks and drinks. 
 
Phase 0 is expected to take approximately 2 months to complete. Phase 1 is expected 
to take approximately 1 year to complete. Phase 2 will begin after Phase 1 data 
collection is completed, and is expected to take approximately 1 year. Phase 3 data 
collection will start after completion of Phase 2, and is also expected to take 
approximately 1 year. 
  
Phase 2A. Investigate the effect of THC on fNIRS brain signature and its association 
with self-reported intoxication, laboratory measures of impairment, and the gold-
standard behavioral field test of driving impairment used by law enforcement, the 
primary classifier.  
 
Participants will come to 101 Merrimac Street for 3 study sessions. At the first visit, 
participants will undergo screening procedures to determine if they’re eligible for the 
study. This will include a medical history interview, substance use history interview 
(timeline follow back), as well as a variety of questionnaires (to be completed by 
participants on study laptop; AUDIT, CUDIT, STAI, HADS, URGE, MEEQ, Who Assist, 
PSQI, CWS). Participant vital signs, height, and weight will be measured, and 
210-270 
min: 
fNIRS 
testing, 
DEQ, 
Vital 
signs 


 12 
participants will also provide a urine sample which will be tested for drugs and 
pregnancy (if applicable) to ensure participants are positive for THC. Participants are 
trained on the driving simulator computer tasks. If participants are determined to be 
eligible, they will be scheduled for the following two visits. In a double-blind, placebo-
controlled, random order cross-over study of single dose THC (dronabinol) at physician 
determined doses of 10-80mg, participants will receive THC capsules or identical 
placebo on two separate study visits, randomized for order. The MGH research 
pharmacy will generate a blinded randomization code for order of dosing and will 
dispense blinded drug in the dose ordered and identical placebo for use on separate 
study days. In order for a complete washout of effects, and to minimize the effect of 
repeat testing for the neuropsychology tasks, study visits must be at least 1 week apart. 
On each study day, participants will have a light standardized breakfast after overnight 
fast and sleep. They will be asked not to deviate from normal behaviors (e.g. if they 
drink caffeinated beverages or smoke cigarettes in the mornings, they will be asked to 
do so on the study day so that no symptoms of caffeine or nicotine withdrawal will 
appear during the scanning period. On each study day, participants will undergo 
baseline fNIRS testing (see above “Cognitive Tasks during FNIRS testing”), substance 
use history interview (timeline follow back), two sets of baseline vital signs, a driving 
simulator computer task refresher, and several questionnaires (HADS, URGE, PSQI, 
CWS). Dronabinol or placebo will be administered once morning procedures are 
complete, after which point heart rate, blood pressure, and responses to DEQ and 
BAES questionnaires will be monitored at 20 minute intervals. The second fNIRS 
session will be conducted at approximately 90 minutes post dose, followed by driving 
simulator computer tasks. A field test of sobriety will be conducted immediately following 
the second fNIRS assessment. The third fNIRS session will be conducted at 
approximately 220 minutes post dose, prior to participant discharge. See Below for 
schematic:  
 
 
 
 
 
 
 
 
 
Subjects who participated in Phase 1 will be eligible for Phase 2, but enrollment in 
Phase 1 is not a requirement for Phase 2. Therefore, new subjects who have not 
completed Phase 1 will also be eligible for Phase 2. 
 
Driving Simulation: During this phase, we will use a computer-programmed driving 
simulator to assess motor coordination of the participants. The simulation will 
programmed in STISIM on the computer and will be administered by a trained research 
coordinator. Subjects will be trained on this task during the screening task during the 
screening visit and given a refresher training on the task before testing. The task is 
performed on a laptop with the use of the keyboard, a joystick, and a foot pedal. 
Pre-Dose: 
fNIRS 
testing, 
interviews, 
vital signs, 
driving sim. 
refresher 
DOSE 
ADMIN 
20 
min: 
DEQ 
& 
BAES
, vital 
signs 
40 
min: 
DEQ 
& 
BAES
, vital 
signs 
60 
min: 
DEQ 
& 
BAES
, vital 
signs 
80 
min: 
DEQ 
& 
BAES
, vital 
signs 
90 min: 
fNIRS, 
driving 
sim., 
field 
sobriety 
220 min: 
fNIRS, 
vital 
signs, 
discharge 
Every 
20 
min: 
DEQ & 
BAES, 
vital 
signs 


 
13 
Participants perform tasks where they must center an object on the screen using the 
joystick, in addition to identifying numbers with the tap of the foot pedal. 
 
Participants: 200 healthy, weekly or greater MJ users, aged 18-55, will be enrolled. 
Participants must test positive for cannabis and have no serious unstable medical 
illness to participate in the Phase II (See Participant Selection Section). 
 
 
Phase 2B. Examine potential interaction following co-administration of THC with oral 
ethanol exposure in healthy volunteers. 
[Design adapted from recently published alcohol interaction studies (Modi et al., 2007; 
Trevisan et al., 2008).] 
 
Phase 2B is a randomized, double-blind, 4-treatment, 4-period, crossover study with 
THC or placebo administration and ethanol or placebo administration. On each of the 4 
study days, participants will be admitted to the Translational and Clinical Research 
Center (TCRC) at Massachusetts General Hospital or the Center for Addiction Medicine 
(CAM). All visits in the TCRC and CAM will be monitored by licensed nursing staff. We 
will provide a breakfast of approximately 400 calories (e.g. juice, cereal, bagel), before 
study procedures begin. 
 
Participants will be assigned randomly to 1 of 4 sequences, and receive each of the 
following treatments: 
o Placebo THC + Ethanol 
o THC + Placebo Ethanol 
o THC + Ethanol 
o Placebo THC + Placebo Ethanol 
We will ensure a washout of at least 1 week between periods. 
 
The process of THC dosing and administration will similar to those as described in 
Phase 2A. Participants will come to 101 Merrimac Street for 5 study sessions. At the 
first visit, participants will undergo screening procedures to determine if they’re eligible 
for the study. This will include a medical history interview, substance use history 
interview (timeline follow back), as well as a variety of questionnaires (to be completed 
by participants on study laptop; AUDIT, CUDIT, STAI, HADS, URGE, MEEQ, Who 
Assist). Participant vital signs, height, and weight will be measured, and participants will 
also provide a urine sample which will be tested for drugs and pregnancy (if applicable) 
to ensure participants are positive for THC. Participants are trained on the driving 
simulator computer tasks. If participants are determined to be eligible, they will be 
scheduled for the following two visits. A study physician will use the information from the 
medical history to determine the dronabinol dose. In addition to this, the physician/nurse 
will also collect a carbon monoxide (CO) measurement to biochemically establish 
smoking status. Dronabinol administration at visits 1-4 in the TCRC or CAM will be the 
same as described in phase 2A. On each study day, participants will undergo baseline 
fNIRS testing (see above “Cognitive Tasks during FNIRS testing”), substance use 
history interview (timeline follow back), baseline vital signs and weight measurement, a 


 14 
driving simulator computer task refresher, and several questionnaires (PSQI, CWS). 
Dronabinol or placebo will be administered once morning procedures are complete, 
after which point heart rate, blood pressure, and responses to DEQ and BAES 
questionnaires will be monitored at 20 minute intervals. ETOH or placebo will be 
administered 60 minutes after dronabinol or placebo. The second fNIRS session will be 
conducted at approximately 100 minutes post dose, followed by driving simulator 
computer tasks. A field test of sobriety will be conducted following the second fNIRS 
assessment. The third fNIRS session will be conducted at approximately 280 minutes 
post dose, prior to participant discharge. See below for schematic: 
 
 
 
 
 
 
 
 
 
 
Ethanol dose and administration: We will obtain a breath alcohol concentration (BrAC) 
of approximately 0.05 BrAC (equal to 1-2 standard drinks). In order to obtain this 
precise BrAC, we will use established methods of dosing based on previously published 
procedures (e.g. King 2005, Alcohol Clin Exp Res, Vol 29, No 4, 2005: pp 547–552).  
 
The required volume of 95% ethanol will be calculated from the nomogram published by 
Watson (1989), and diluted to a final concentration of 20% by volume with diet soda. 
The nomogram is based on total body water, estimated for each subject using standard 
equations based on gender, age, height, and weight (Watson et al., 1980). Doses will 
be prepared at the TCRC  by a licensed nutritionist or at CAM by unblinded study staff. 
He/she will determine the dose according to our spreadsheet for dosing (attached).  
 
In an attempt to standardize the drinking time to 8 minutes, the total dose will be split 
into 4 equal aliquots and placed in cups with lids. The subject will be given a cup every 
2 minutes with instructions to sip the drink using a straw.  
 
• Placebo Ethanol drink will be made as an equal volume of diet soda placed in 
identical cups with lids and straws. 0.25 ml of 95% ethanol should be floated on 
the top of the soda in each cup in an attempt to blind the participant. 
 
The alcohol administration procedure will take place approximately 45 min before the 
start of the second fNIRS session. Before being administered alcohol, study staff will 
measure breath alcohol levels. Additionally, a study physician/nurse will assess subjects 
at each study visit prior to any study drug administration for signs of intoxication. 
Subjects will be terminated from the study if BrAC > 0 or if they exhibit clinical signs of 
intoxication at time of arrival for study visit. 
 
Pre-Dose: 
fNIRS 
testing, 
interviews, 
vital signs, 
driving sim. 
refresher 
Dronabinol
20 
min: 
DEQ 
& 
BAES
, vital 
signs 
40 
min: 
DEQ 
& 
BAES
, vital 
signs 
60 
min: 
ETOH, 
DEQ 
& 
BAES, 
vital 
80 
min: 
DEQ 
& 
BAES
, vital 
signs 
100 
min: 
fNIRS, 
driving 
sim., 
field 
sobriety 
280 min: 
fNIRS, 
vital 
signs, 
discharge 
Every 
20 
min: 
DEQ & 
BAES, 
vital 
signs 


 
15 
During this phase, breathalyzer measurements will be taken approximately every 20 
minutes after the alcohol administration procedure, until BrACs have returned to <0.01. 
Participants will be required to stay in the laboratory until BrACs have returned to <0.01. 
A member of our study staff will then (1) arrange cab service that has an approved 
partnership with MGH, and (2) escort the participant to the cab at the end of the study 
visit. Alternatively, it would be acceptable for participants to arrange travel home with a 
family member or friend. If they choose to do this, a study staff member will ensure that 
someone is there to bring them home prior to departure.  
 
The dronabinol capsules will be taken approximately 60 minutes before the alcohol 
administration procedure will begin, so that peak effects of each drug will be concurrent.  
 
Driving Simulation: During this phase, we will use a computer-programmed driving 
simulator to assess motor coordination of the participants. The simulation will 
programmed in STISIM on the computer and will be administered by a trained research 
coordinator. Subjects will be trained on this task during the screening task during the 
screening visit and given a refresher training on the task before testing. The task is 
performed on a laptop with the use of the keyboard, a joystick, and a foot pedal. 
Participants perform tasks where they must center an object on the screen using the 
joystick, in addition to identifying numbers with the tap of the foot pedal. 
 
Blood Draw: During this phase, we will collect blood samples to track THC levels 
throughout the study. All blood samples will be taken by a catheter inserted in a forearm 
vein by a licensed nurse. One mL of blood will be taken pre-dose and approximately 
every 20-40 minutes post-dose until 300 minutes post-dose: 0, 40, 80, 100, 130, 160, 
190, 210, 260, 300, for a total of 10 mL. Collected blood samples will be processed by 
an outside company, Immunalysis Corporation, to test for plasma concentrations of 
delta-9 THC. 
 
Participants: 200 healthy, weekly or greater MJ users, aged 21-55, will be enrolled. 
Participants must test positive for cannabis and have no serious unstable medical 
illness to participate in Phase 2B (See Participant Selection Section). 
 
Subjects who participated in Phase 1 or 2A will be eligible for Phase 2B, but enrollment 
in Phase 1 or 2A is not a requirement for Phase 2B.  Therefore, new subjects who have 
not completed Phase 1 or 2A will also be eligible for Phase 2B so long as they are over 
the age of 21. Subjects who enroll in more than one phase of the study will be (1) re-
consented for each phase and (2) counted again toward enrollment targets (i.e., 
counted toward the enrollment target listed for each study phase). 
 
 
Phase 3. Investigate at which doses of dronabinol an effect on neurocognitive task 
performance or an effect on PFC activity can be observed. 
 
Procedures will be identical to those of Phase 1 except that subjects will be scheduled 
for 3 study sessions. In each study session, they will be given a low, medium, or high 


 16 
dose of dronabinol (20 mg, 35 mg, 50 mg). In this single-blinded phase, the subject will 
not know which dose he/she is receiving. The protocol for the study visit will be 
identical. As there are three levels of drug exposures, there are 6 possible orders in 
which subjects can receive the three doses (e.g. high, medium, low; medium, low, high; 
etc). Subjects will be randomly assigned to one of the 6 possible orders according to a 
randomization schedule generated by the study staff using a random number generator 
and computer program. In order for a complete washout of effects, and to minimize the 
effect of repeat testing for the neuropsychology tasks, study visits must be at least 1 
week apart. See below for schematic: 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects who participated in Phase 1 or 2 will be eligible for Phase 3, but enrollment in 
Phase 1 or 2 is not a requirement for Phase 3.  Therefore, new subjects who have not 
completed Phase 1 or 2 will also be eligible for Phase 3. 
 
Driving Simulation: During this phase, we will use a computer-programmed driving 
simulator to assess motor coordination of the participants. The simulation will 
programmed in STISIM on the computer and will be administered by a trained research 
coordinator. Subjects will be trained on this task during the screening task during the 
screening visit and given a refresher training on the task before testing. The task is 
performed on a laptop with the use of the keyboard, a joystick, and a foot pedal. 
Participants perform tasks where they must center an object on the screen using the 
joystick, in addition to identifying numbers with the tap of the foot pedal. 
 
Participants: 60 healthy, weekly or greater MJ users, aged 18-55, will be enrolled. 
Participants must test positive for cannabis, and negative for other addictive drugs and 
have no serious unstable medical illness to participate in the Phase III (See Participant 
Selection Section). 
 
Biostatistical Analysis 
Data variables collected for study 
Standardized questionnaires, assessing drug use, personality characteristics, and 
anxiety will be collected, as well as task data and neural signaling data from the fNIRS 
testing sessions. 
 
210-270 
min: 
fNIRS 
testing, 
DEQ, 
Vital 
signs 


 
17 
All data will be collected and managed using REDCap electronic data capture tools 
(Harris 2009) hosted with Partners HealthCare.  
 
Vanderbilt University, with collaboration from a consortium of institutional partners, has 
developed a software toolset and workflow methodology for electronic collection and 
management of research and clinical trial data. REDCap (Research Electronic Data 
Capture) 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. 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. 
 
fNIRS Data Analysis 
The instrument will acquire raw data for each detector at ~40 kHz. The individual source 
signals then will be obtained with a digital bandpass filter – for example, a discrete 
Fourier transform or an infinite-impulse-response filter. The individual source signals will 
be separated off-line with an infinite-impulse-response filter with a 50 Hz band pass 
frequency.  Next, the time series pairs from each detector will be converted from 
wavelength (absorption) to relative concentrations (of oxy-/deoxy-hemoglobin).  This will 
be done with the modified Beer-Lambert Law and the absorption coefficients of oxy- and 
deoxy-hemoglobin (HbO and Hb, respectively) [34].  (The near-IR wavelengths are 
chosen because oxy-/deoxy-Hb are the predominant absorbers in the tissue at these 
wavelengths.)  The result will be an oxy-Hb and deoxy-Hb timeseries associated with 
each source-detector pair. 
 
For each stimulation run, each smoothed oxy-/deoxy-hemoglobin time series will be 
examined for periodic amplitude fluctuations.  Expected fluctuations include heart rate 
(~1Hz), breathing and/or “v-waves” (~0.1Hz), as well as any fluctuations induced by the 
experimental paradigm.  If the former sources of noise are substantial, an attempt will 
be made to filter out these fluctuations (in Fourier space).  Any analysis of filtered data 
will be compared to an analysis of the corresponding non-filtered data.  The oxy-
hemoglobin portion of the experimentally induced changes are expected to be 4-9 sec 
out of phase with the paradigm onsets and offsets (as seen in fMRI work as well as in 
prior optical recordings).   
 
Study endpoints 
As this is not a clinical trial, we will collect data from up to 20 participants in Phase 0, up 
to 100 participants in Phase I, up to 200 in Phase II and up to 60 in Phase III in order to 
investigate whether we can determine the brain signals involved in marijuana 
intoxication. Given that the planned studies are pilot in nature, and that we will be using 


 18 
a recently developed instrument, the relevant effect sizes are unknown and therefore 
power analysis cannot be adequately performed.  However, some estimates can be 
made.  The biological basis for the signals measured by the optical technique is the 
same as the basis for fMRI and PET scanning. In a similar study using PET (R.J. 
Mathew et al. / Psychiatry Research: Neuroimaging 116 (2002) 173–185), indices of 
rCBF, intoxication and physiology were measured at baseline and 30, 60, 90 and 120 
min. after an intravenous infusion of 0.15 or 0.25 mg of THC, or placebo. Significant 
increases were seen in global perfusion and in the frontal, insular and anterior cingulate 
regions. This study had a sample size of 47 subjects in each group. Therefore, we will 
collect data in 100 participants, as this is a conservative estimate of the power we will 
need to detect an effect. 
 
Statistical methods 
Statistical analysis of data will be performed using SPSS, STATA, and fNIRS analysis 
software. 
 
Risks and Discomforts 
 
 
Potential adverse events due to dronabinol: 
 
Risks: Dronabinol-induced sympathomimetic activity may result in tachycardia and/or 
conjunctival injection. Its effects on blood pressure are inconsistent, but occasional 
subjects have experienced orthostatic hypotension and/or syncope upon abrupt 
standing. Dronabinol also demonstrates reversible effects on appetite, mood, cognition, 
memory, and perception. These phenomena appear to be dose-related, increasing in 
frequency with higher dosages, and subject to inter-patient variability. 
 
After oral administration, dronabinol has an onset of action of approximately 0.5 to 1 
hours and peak effect at 2 to 4 hours. Duration of action for psychoactive effects is 4 to 
6 hours. 
 
Tachyphylaxis and tolerance develop to some of the pharmacologic effects of 
dronabinol and other cannabinoids with chronic use, suggesting an indirect effect on 
sympathetic neurons. In a study of the pharmacodynamics of chronic dronabinol 
exposure, healthy male volunteers (N = 12) received 210 mg/day dronabinol, 
administered orally in divided doses, for 16 days. An initial tachycardia induced by 
dronabinol was replaced successively by normal sinus rhythm and then bradycardia. A 
decrease in supine blood pressure, made worse by standing, was also observed 
initially. These volunteers developed tolerance to the cardiovascular and subjective 
adverse CNS effects of dronabinol within 12 days of treatment initiation. 
 
In the clinical trials, the majority of patients were treated with 5 mg/day MARINOL 
Capsules, although the dosages ranged from 2.5 to 20 mg/day.  
 


 
19 
Minimization: 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, or another study physician) 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 for the situation. There is a licensed physician/registered nurse 
on site 40 hours per week, and other MGH resources can be used as necessary. 
 
Potential adverse events due to ethanol: 
Risks: At low to moderate doses, ethanol can produce behavioral intoxication and 
physiological changes (feeling intoxicated, high, euphoric, dizzy, giddy, tired and 
lightheaded; increased heart rate, slurred speech, and slowed reaction time).  These 
effects will not be novel to our subjects who will have experience drinking. The amount 
of alcohol administered is similar to that experienced by casual users of this drug and is 
fairly low for moderate to heavy users.   
Minimization: Participants will not be required to perform any physical tasks while 
intoxicated. Drinking alcohol under controlled laboratory conditions is unlikely to change 
current use patterns or cause addiction. 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, or 
another study physician) to determine appropriate steps. These investigators will handle 
any adverse reaction (physical or psychological) to the drug administration. 
 
 
Psychosocial risks 
Risks: There is no social risk associated with participation in this study. There are few 
legal risks to the participants associated with these paradigms. Cannabis use is 
decriminalized in Massachusetts, thus there is no legal risk to self-report of regular 
cannabis use. However, a possible risk is that subjects may come up positive on a 
workplace drug screen if they take part in this study. 
Minimization: We will provide subjects with documentation that describes the study 
procedures, and states that participation in this study will affect any drug screen results. 
 
Confidentiality and Loss of Privacy 
Risks: The risk of loss of privacy is judged to be minimal.  
Minimization: Confidentiality will be maintained by numerically coding all data and by 
keeping all data in locked file drawers and deidentified 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.  
 
fNIRS Risks 
Risks: fNIRS is a minimal risk procedure. fNIRS assess the brain's hemodynamic 
response by employing optical properties of light. Unlike fMRI, fNIRS only collects data 
~3 cm into the cortex. fNIRS employs non-ionizing near-infrared light, so no 
cancerogeneous or genetic effects are possible. The light intensity is kept well below 


 20 
safety limits to avoid the risk of thermal damages. No cumulative harmful effects of such 
light exposure to the forehead are known, and fNIRS measurements are commonly 
applied repeatedly or in a continuous manner for monitoring purposes. 
  
Minimization: Subjects who may become uncomfortable during the fNIRS procedure will 
be able to converse with the experimenter and will be able to communicate any desire 
or need to stop the procedure. All efforts will be made to make the subjects as 
comfortable as possible. A member of the study staff will explain the procedure 
thoroughly to the subject, allowing for maximal understanding and comfort. The testing 
can be stopped at any time at the subjects’ request. A qualified physician/nurse will be 
on site or reachable by pager during all study visits in the unlikely event that an adverse 
event occurs. 
 
The likelihood for the need for medical or professional intervention for a participant in 
this study is reduced by the protocol enrollment criteria that specify that we will enroll 
only medically stable, healthy adults to the study. Subjects will be asked to report 
adverse events at any time by calling study staff and will be asked to report adverse 
events at each study visit.  
 
Risks of blood draws 
Risks: The discomfort associated with removing (by catheter from a vein) is a slight 
pinch or pin prick when the sterile needle enters the skin. The risks include mild 
discomfort and/or a black and blue mark at the site of puncture. Less common risks 
include a small blood clot, infection or bleeding at the puncture site, and on rare 
occasions fainting during the procedure. There will be only a small amount of blood 
drawn (about 1 mL) each time.  
 
Minimization: Blood draws will be taken by trained nursing staff at the Translational and 
Clinical Research Center or Center for Addiction Medicine at Massachusetts General 
Hospital. The total amount of blood drawn will not exceed 5 ccs per draw or 45 ccs per 
study day. 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 to determine appropriate steps. 
 
Potential Benefits 
There is no direct benefit to participating in this research. Some 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 to the field of actute 
marijuana effects on the brain.  
 


 
21 
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 minor or 
significant adverse event the PI will be contacted immediately. The PI is responsible for 
the generation of summary reports to the Partners HRC and to NIH, documenting this 
process and outcome. 
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.   

SAP_003.pdf: 
Running head: STATISTICAL ANALYSIS PLAN 
1
 
Using Imaging to Assess Effects of THC on Brain Activity (fNIRS) 
Statistical Analysis Plan 
The fNIRS Team 
Version 1 
First version: 4/29/2022 
Latest version: 4/29/2022 
ClinicalTrials.gov ID: NCT03655717 
Unique protocol ID: 2015P001516 
U.S. NIH Grant/Contract Award Number: R42DA043977 
 
 


STATISTICAL ANALYSIS PLAN 
2
 
Table of contents 
 
Table of contents .............................................................................................................................. 2 
Glossary ............................................................................................................................................ 3 
Study Design ..................................................................................................................................... 4 
Participants ................................................................................................................................... 4 
Analytic Approach ............................................................................................................................. 5 
Primary Outcomes ........................................................................................................................ 5 
Statistical Model ...................................................................................................................... 5 
Covariates ................................................................................................................................ 6 
Missing Data ............................................................................................................................. 6 
Sample Size Determination .............................................................................................................. 7 
Software ............................................................................................................................................ 8 
References ........................................................................................................................................ 9 
 
 
 
 


STATISTICAL ANALYSIS PLAN 
3
 
Glossary 
Abbreviation 
Label 
ETOH 
Alcohol 
FDA 
Federal Drug Administration 
fNIRS 
Functional near-infrared spectroscopy 
HbO 
Oxygenated hemoglobin 
PFC 
Pre-frontal cortex 
THC 
Tetrahydrocannabinol 
 
 
 


STATISTICAL ANALYSIS PLAN 
4
 
Study Design 
This study will assess the effects of THC intoxication using dronabinol (synthetic THC) on the 
HbO signal during resting state and task-based activation in the prefrontal cortex (PFC), resting state 
connectivity, neurocognitive task performance, clinical signs of intoxication, and correlations between 
these measurements. Participants will be given up to 80 mg of dronabinol, an FDA-approved synthetic 
form of THC that is used to treat loss of appetite that causes weight loss in people with AIDS. THC is the 
principle psychoactive drug in marijuana. The study will be conducted in regular cannabis users who 
present at the screening visit with a positive urine screen for THC metabolites. Data will be collected 
over two phases: 
• 
Phase 2A is a randomized, double-blind, placebo-controlled, study of effect of 
dronabinol vs placebo. This phase will investigate the effect of THC on fNIRS brain 
signature and its association with self-reported intoxication, laboratory measures of 
impairment, and the gold-standard behavioral field test of driving impairment used by 
law enforcement. 
• 
Phase 2B is a randomized, double-blind, placebo-controlled, 2 by 2 crossover study of 
effect of dronabinol, ethanol, and combined dronabinol and ethanol on brain activation 
and connectivity as measured by fNIRS. Phase 2B will examine potential interaction 
between THC and alcohol following co-administration of THC with oral ethanol exposure 
in healthy volunteers.  
Participants 
Participants will be 150 adults who use marijuana at least monthly (aged 18-55) will be recruited 
to participate in this study. 
 
 


STATISTICAL ANALYSIS PLAN 
5
 
Analytic Approach 
Primary Outcomes 
The primary outcomes for the study will be… 
1. The mean HbO level averaged over the duration of the N-back task scan (approximately 
2938 samples taken over 376 seconds in 128 millisecond intervals). 
2. The mean HbO level averaged over the duration of the resting state scan (2814 samples 
taken over 360 seconds in 128 millisecond intervals). 
Mean HbO levels for both outcomes will be determined over (a) four conditions administered 
over separate visits about a week apart (where participants could be dosed with placebo, THC only, 
ETOH only, or both THC and ETOH), and (b) two scans per condition: A scan prior to and approximately 
100 minutes after being dosed. Higher HbO levels indicate a greater degree of neural activity in the PFC 
regions of the brain. 
 
Statistical Model 
We will analyze both primary outcomes using a multi-level linear regression model with subject-
varying intercepts estimated via maximum likelihood. The key exposures are whether a person was 
dosed with placebo, THC, ETOH, or the combination of THC and ETOH. Table 1 lists the numeric coding 
used to test our planned contrasts. All terms will be coded as 0 for pre-dose scans, as no combination of 
drugs will have been administered. 
Table 1: Design matrix for testing key exposures 
Scan 
Dose 
Main effects 
 
Interaction 
 
 
THC 
ETOH 
THC x ETOH 
Post-dose 
Placebo 
0 
0 
0 
 
THC 
1 
0 
0 
 
ETOH 
0 
1 
0 
 
THC + ETOH 
1 
1 
1 
 


STATISTICAL ANALYSIS PLAN 
6
 
Statistical significance for each contrast will be determined via a non-parametric bootstrap 
procedure for robustness. First, each subject’s set of completed condition (placebo, THC, ETOH, THC + 
ETOH) will be randomly shuffled across their set of visits. Second, the shuffled data will be refit with the 
multi-level model, and coefficient estimates will be obtained for the key exposures. Third, the prior two 
steps will be repeated 10,000 times, providing a null distribution to compare the observed coefficient 
estimates against. The p-values for the key exposures will be estimated as P(|o| < |si|), where o is the 
observed coefficient, and si is the ith coefficient from the shuffled data. For each outcome there will be 
3 p-values (the main effects of THC and ETOH and their interaction). The total set of 6 p-values will be 
adjusted for multiple comparisons using the Benjamini-Hochberg method (Benjamini & Hochberg, 
1995). An adjusted p-value < 0.05 will indicate a statistically significant effect of either THC, ETOH, or 
their interaction on neural activity in the PFC. 
Covariates 
We will include two sets of covariates in our model. First, we will include a dummy-coded 
contrast comparing pre-dose scans (coded as 0) to post-dose scans (coded as 1). Second, we will include 
covariates adjusting for visit order. The referent will be the first visit (coded as -1), and we will include 
three terms for the second, third, and fourth visit (coded as 1 for the given visit and 0 otherwise). All 
terms will then be converted to z-scores. 
 
Missing Data 
We will only include data from complete visits with both pre-dose and post-dose scans. 
Participants with no complete pairs of pre and post-dose scans for any conditions will be excluded from 
the analyses. Missingness will be naturally handled by the multi-level modeling approach, as the higher 
order terms governing the random effects provide shrinkage and information even in the presence of 
missing cases (Baayen, Davidson, & Bates, 2008). 


STATISTICAL ANALYSIS PLAN 
7
 
Sample Size Determination 
Sample size was pre-specified in our grant application. Since no prior studies have attempted to 
predict impairment using fNIRS measurements, we did not have an effect estimate with which to 
determine sample size. In order to maximize the chance that standard methods could detect an effect of 
intoxication on PFC activation patterns with the N-Back task, we collected as many scans as possible 
with the R42 grant funds allotted. 
 
 


STATISTICAL ANALYSIS PLAN 
8
 
Software 
All analyses will be done using the statistical software R (version 4.1.1; R Core Team, 2021) and 
integrated development environment RStudio (version 2020.9.0.351; RStudio Team, 2021). Data will be 
prepared using the R packages ‘dplyr’ (version 1.0.7; Wickham, François, Henry, & Müller, 2021. Models 
will be fit using the R package ‘lme4 (version 1.1-27.1; Bates, Maechler, Bolker, & Walker, 2015).  
 
 


STATISTICAL ANALYSIS PLAN 
9
 
References 
Baayen, R. H., Davidson, D. J., & Bates, D. M. (2008). Mixed-effects modeling with crossed random 
effects for subjects and terms. Journal of Memory and Language, 59 (4), 390-412. 
https://doi.org/10.1016/j.jml.2007.12.005 
Bates, D., Maechler, M., Bolker, B., & Walker, S. (2015). Fitting linear mixed-effects models using lme4. 
Journal of Statistical Software,  67 (1), 1-48. https://doi.org/10.18637/jss.v067.i01. 
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful 
approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological), 
57 (1), 289-300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.x. 
R Core Team (2021). R: A language and environment for statistical computing [Computer software]. 
https://www.R-project.org. 
RStudio Team. (2021). RStudio: Integrated development environment for R (version 2020.9.0.351) 
[Computer software]. RStudio, PBC. http://www.rstudio.com/ 
Wickham, H., François, R., Henry, L. & Müller, K. (2021). dplyr: A grammar of data manipulation (version 
1.0.7). [Computer software] Retrieved from  
https://cran.r-project.org/web/packages/dplyr/index.html 

ICF_004.pdf: 
Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 1 of 13
Subject Identification
Protocol Title: Using Imaging to Assess Effects of THC on Brain Activity 
(Phase 2A)
Principal Investigator: Jodi Gilman, Ph.D.
Site Principal Investigator:      
Description of Subject Population: Healthy Adults ages 18-55
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.
Why is this research study being done?
The purpose of the study is to help us learn about the effects of marijuana on the brain. We hope 
to better understand certain brain regions that are important in decision-making and cognition, 
and how they are affected by marijuana intoxication. We are asking you to take part in this 
research study because you are a healthy adult between the ages of 18 and 55 who has used 
marijuana in the past. About 130 people will take part in this research study. This is a pilot study, 
which is a small scale preliminary study conducted in order to evaluate feasibility, time, cost, 
adverse events, and effect size (statistical variability) in an attempt to improve upon the study 
design prior to performance of a full-scale research project.
The National Institute on Drug Abuse and Brain Solutions, LLC are paying for this study to be 
done. These funding sources will have no role in the study design, collection, analysis or 
interpretation of the data.
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 2 of 13
Subject Identification
Drs. Evins and Gilman, investigators on this study, are developing the technology that is used in 
this study for a potential method for detecting cannabis intoxication. Drs. Evins and Gilman have 
a financial interest in Brain Solutions, the company that is sponsoring this study. Drs. Evins, 
Gilman, Brain Solutions, and the hospital may benefit financially if this study shows that the 
technology is valuable. The hospital’s conflict of interest policies are handled by the hospital’s 
owner, Partners HealthCare. In accordance with these policies, Partners has determined that the 
interests create no significant risk to the welfare of participants in this study or to the integrity of 
the research. If you want more information about this, please contact the Partners Office for 
Interactions with Industry at PHSOII@partners.org, 857-282-2024. 
How long will I take part in this research study?
This phase of the study consists of three visits at MGH. The first visit is a screening visit where 
we will determine if you’re eligible for the study. This visit will last about 3 hours. The next two 
visits will be at least 1 week apart. At each of these visits, you will be given either a physician 
determined dose of dronabinol or a placebo. Dronabinol is a capsule that has the psychoactive 
ingredient in marijuana, called THC. A placebo is an inactive substance, which does not contain 
medication and looks like the active study drug. For research to be good, it is important that you 
do not know whether you have been given the active study drug, Dronabinol, or the placebo, the 
pretend medicine. This is one of the best ways we have to study the effects of marijuana on the 
brain. It will take you about 7 hours to complete each of these study visits. The 7 hours includes 
interviews, questionnaires, and the brain imaging assessments. You will have breaks for snacks 
and drinks in between testing periods. 
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. Please see below for details on texting. During the 
study, we will ask you to:

Fill out questionnaires

Answer questions about your medical and psychiatric health

Provide a urine sample to check for illegal drug use and pregnancy (in females)
- This urine drug screen test result will not become part of your medical record
- This pregnancy test result will not become part of your medical record

Take a dronabinol capsule, which may contain THC or placebo

Participate in cognitive testing while your brain function is measured a technology called 
functional near-infrared spectroscopy (fNIRS).
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 3 of 13
Subject Identification

Complete a computer game that simulates driving

Complete a brief evaluation to assess your level of impairment
Texting:
Text messages by mobile/cell phones are a common form of communication. The fNIRS 
research study involves sending you text messages that are relevant to the research study.    
Texting over mobile/cell phones carries security risks because text messages to mobile/cell 
phones are not encrypted.  This means that information you send or receive by text message 
could be intercepted or viewed by an unintended recipient, or by your mobile/cell phone provider 
or carrier. 
Below are some important points about texting in this research study. 

Text messages are not encrypted, and therefore carry security risks. This research study and 
Partners Healthcare are not responsible for any interception of messages sent through 
unencrypted text message communications.  

You will be responsible for all fees charged by your carrier’s service plan for text 
messaging.  This research study and Partners Healthcare are not responsible for any 
increased charges, data usage against plan limits or changes to data fees from the 
research texts 

Text messages will only be read during regular business hours. The texting service can only 
interpret the number 1 to confirm the appointment or 3 to reschedule the appointment. If 
you need to send alternative messages, please communicate over email. 

Text messaging should not be used in case of an emergency.  If you experience a medical 
emergency, call 911 or go to the nearest hospital emergency department.  

You may decide to not send or receive text messages with staff associated with this research 
study at any time. You can do this in person or by sending the research email a message that 
says “Stop Research Text.” 

Your agreement applies to this research study only.  Agreeing to other texts from Partners 
Healthcare, for example appointment reminders, is a separate process.  Opting out of other 
texts from Partners Healthcare is a separate process as well.

It is your responsibility to update your mobile/cell phone number with this research study in 
the event of a change.
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 4 of 13
Subject Identification
Do we have your permission to send you text reminders to your cell phone?
  YES
 NO
Initials_________________
Questionnaires:
First, you will fill out questionnaires that ask you about your personality, mood, and drug and 
alcohol use. Two of these questionnaires will ask you about how you are feeling and whether 
you feel any effects of the dronabinol capsule. These questionnaires will be repeated throughout 
the study before you take the capsule and then every 20 minutes (before and after brain imaging) 
for the rest of the study.
Dronabinol Capsule:
Dronabinol contains synthetic THC, which is the main psychoactive compound in marijuana. 
Dronabinol is approved by the U.S. Food and Drug Administration (FDA), and is used for 
appetite stimulation in AIDS patients and to treat nausea and vomiting in patients receiving 
chemotherapy. Doses similar to the one you will be given produce symptoms of intoxication 
such as laughing, elation and subjective heightened awareness. 
You will receive either THC capsules or identical placebo on two separate study visits, 
randomized for order. This study is double-blind, placebo-controlled, random order cross-over 
study. This means that neither you nor the study doctor or study staff will know which study 
drug you have received. You will receive either dronabinol or the placebo after the first round of 
questionnaires and fNIRS imaging. A timeline is specified below.
Because Dronabinol contains the psychoactive ingredient in marijuana, you are asked to refrain 
from using marijuana within 24 hours of the study visit. This is for your safety. If you have used 
marijuana within 24 hours, you may be asked to reschedule your study visit. 
Brain Imaging Assessment:
We will take pictures or images of your brain using an fNIRS machine. 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. Each fNIRS test will take about 30 minutes, and we will do testing at 
3 or 4 timepoints during the study visit. We will test everyone at 3 timepoints: before you take 
the capsule, at the peak of the capsule’s effects on the brain, and 1.5 hours after the peak brain 
effects, when most people will no longer feel the drug effects. Some people may still feel high or 
intoxicated during the third session of testing. If you still feel high or intoxicated, it may be 
necessary to repeat a 4th session of testing when you no longer feel the effects of the drug. 
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 5 of 13
Subject Identification
The timeline of these procedures is as seen below. You will have breaks after each fNIRS 
session where you will be able to get food and drinks.
Before beginning the first fNIRS scan, you will be seated comfortably in a chair and we will 
place a cap on your head. The cap holds the “optodes,” instruments that give off light and also 
receive and measure light. The cap is made of fabric and has velcro straps.  Because hair and 
scalp coloring might interfere with light measurements, we may need to adjust the cap after we 
put it on. We will keep checking until there is no interference. We will ask you to do some tasks. 
These tasks may consist of counting numbers, reciting words with a certain letter or in a certain 
category, or playing games on a computer that require you to make decisions about objects on 
the screen, such as the direction of arrows. If we can’t get a good signal with our equipment, then 
we will stop the procedure and take you out of the study. Once we get a good signal we will 
apply the different types of stimuli as described above. This will be performed in the dark 
because the fNIRS equipment is sensitive to all types of light. When the testing is over, the cap 
will be removed from your head.
Below is a photograph of the NIRS device and how it is worn.
Driving Simulation: We will use a computer-programmed driving simulator game to assess 
your motor coordination. This computer program simulates tasks that are relevant to driving 
using the keyboard, a foot pedal, and a joystick.
Pre-Dose:
fNIRS 
testing, 
interviews, 
vital signs, 
driving sim. 
refresher
DOSE 
ADMIN
20 
min:
DEQ 
& 
BAES
, vital 
signs
40 
min:
DEQ 
& 
BAES
, vital 
signs
60 
min:
DEQ 
& 
BAES
, vital 
signs
80 
min:
DEQ 
& 
BAES
, vital 
signs
90 min:
fNIRS, 
driving 
sim., 
field 
sobriety
220 min:
fNIRS, 
vital 
signs, 
discharge
Every 
20 
min:
DEQ & 
BAES, 
vital 
signs
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 6 of 13
Subject Identification
Information Storage
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. 
Your information may be kept for several decades.
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 study staff by phone 
at (617) 643-1984, or by email at fnirsstudy@partners.org. 
Disclosure of Results
Your individual research results will never be shared with you or entered into your medical 
record.
What are the risks and possible discomforts from being in this research 
study?
Risks of dronabinol: Dronabinol can increase your heart rate and/or result in bloodshot eyes. 
Some people experienced lowering in blood pressure, lightheadedness, fainting, falling upon 
abrupt standing, nausea, and vomiting. The likelihood that these problems may occur can be 
reduced by making sure you drink enough fluids. Dronabinol also has a reversible effect on 
appetite, mood, cognition, memory and perception. These effects are more pronounced at higher 
doses of dronabinol. They are also related to individual differences in how we break down 
(metabolize) the drug. In this study, we will use a high dose of dronabinol, so you may notice 
some of these effects. 
If there are any concerns that you are in need of clinical attention, the PI will be made aware of 
the issue immediately and will consult with a physician (co-investigator: A. 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 
appropriate for the situation. There is a licensed physician or licensed, registered nurse on site 
during your testing, and other MGH resources can be used as necessary.
An additional risk of participating in this study is that you may come up positive on a workplace 
drug screen as a result of taking a dronabinol capsule. If you choose, we can provide you with 
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 7 of 13
Subject Identification
documentation that describes the study procedures, and states that participation in this study will 
affect any drug screen results.
There is a paucity of data about the safety of administering dronabinol to pregnant women. Due 
to the possible risks to an embryo or fetus, or to an infant who is being breastfed, you will be 
excluded if you are currently breastfeeding or are/may become pregnant. 
You should not drive, operate machinery, or engage in any hazardous activity until you can 
perform such tasks safely. A member of our study staff will: (1) arrange cab service that has an 
approved partnership with MGH, and (2) will escort you to the cab at the end of the study visit. 
Alternatively, it would be acceptable for you to arrange travel home with a family member or 
friend. If you choose to do this, a study staff member will ensure that someone is there to bring 
you home prior to your departure.
In the investigators opinion, repeated exposure to dronabinol (two doses at least one week apart) 
does not involve increased risk to the adult participants who report using cannabis, often in much 
higher doses and of unknown purity, on a regular basis, often multiple times per day.
Risks of placebo: Placebo is a gelcap capsule filled with the same oil that is in Dronabinol, but 
without THC. 
Risks of fNIRS: fNIRS is not considered to be risky. You are no more likely to be harmed than 
you are while performing everyday tasks. The system we will use in this study is a new 
experimental way to measure activity in the brain. No harmful effects have been reported so far, 
but it is possible that you may experience side effects that haven’t been reported yet. The light 
used is considered to be harmless – it is much less intense than the sunlight you would feel 
during an outdoor walk on a sunny day. It is possible that you may experience minor temporary 
skin irritation from the glue or tape which we use to attach the monitor and electrodes to the 
head.
We will not share your identity with anyone outside the Partners institutions. No record of your 
results from this research study will enter your medical records. However, we cannot guarantee 
your confidentiality.
What are the possible benefits from being in this research study?
You will not directly benefit from taking part in this research study. Researchers may benefit 
from what we learn in this research study. 
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 8 of 13
Subject Identification
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 by check at the completion of the study for your participation. You will be paid 
$25 for the screening visit, $100 for the first 7-hour visit, and $100 for the second 7-hour visit. 
This means that you can earn up to $225 in total if you participate in all study visits. You will 
also be provided transportation on the way home from the study visit, unless you decide to 
arrange a ride with a friend or family member. If you choose to do this, a study staff member will 
ensure that someone is there to bring you home prior to your departure. If you come in for the 
study but are found to be ineligible, you will be paid for the screening only ($25).
What will I have to pay for if I take part in this research study?
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.
What happens if I am injured as a result of taking part in this research 
study?
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 9 of 13
Subject Identification
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, Ph.D. 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 
would like to speak to a physician, you can call Dr. Eden Evins at 617-643-4679, Monday 
through Friday 9AM to 5PM. If you need to speak to someone after office hours in an emergency 
you can call 617-726-2000 and ask the operator to page Dr. Evins. 
If you have questions about the scheduling of appointments or study visits, call our study staff at 
(617) 643-1984.
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
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 10 of 13
Subject Identification
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

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:       
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 11 of 13
Subject Identification
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.
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
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 12 of 13
Subject Identification
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.

I have had the chance to ask questions about texting with staff associated with this 
research study.  I have been informed of the risks and other information covered above 
and consent to the use of unencrypted text communications associated with this research 
study.
Study Information Included in Your Electronic Medical Record
A notation that you are taking part in this research study may be made in your electronic medical
record. Information from the research that relates to your general medical care may be included
in the record (for example: list of allergies, study medication). Following completion of the 
study, information pertaining to your involvement with the study will be removed from your 
medical record, including mention of study medication.
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 (optional)
Signature of Study Doctor or Person Obtaining Consent:
Statement of Study Doctor or Person Obtaining Consent
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 13 of 13
Subject Identification

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 (optional)
Certificate of Confidentiality:
A federal Certificate of Confidentiality (Certificate) has been issued for this research 
to add special protection for information and specimens that may identify you. With a 
Certificate, unless you give permission (such as in this form) and except as described 
above, the researchers are not allowed to share your identifiable information or 
identifiable specimens, including for a court order or subpoena. Certain information 
from the research will be put into your medical record and will not be covered by the 
Certificate. This includes records of medical tests or procedures done at the hospitals 
and clinics, and information that treating health care providers may need to care for 
you. Please ask your study doctor if you have any questions about what information 
will be included in your medical record. Other researchers receiving your identifiable 
information or specimens are expected to comply with the privacy protections of the 
Certificate. The Certificate does not stop you from voluntarily releasing information 
about yourself or your participation in this study.
Consent Form Version:  3/3/2020
Consent Form Title: fNIRS_consent2A_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 1 of 15
Subject Identification
Protocol Title: Using Imaging to Assess Effects of THC on Brain Activity 
(Phase 2B)
Principal Investigator: Jodi Gilman, Ph.D.
Site Principal Investigator:      
Description of Subject Population: Healthy Adults ages 21-55
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.
Why is this research study being done?
The purpose of the study is to help us learn about the effects of marijuana on the brain. We hope 
to better understand certain brain regions that are important in decision-making and cognition, 
and how they are affected by marijuana and alcohol intoxication. We are asking you to take part 
in this research study because you are a healthy adult between the ages of 21 and 55 who has 
used marijuana and alcohol in the past. About 60 people will take part in this research study. 
This is a pilot study, which is a small scale preliminary study conducted in order to evaluate 
feasibility, time, cost, adverse events, and effect size (statistical variability) in an attempt to 
improve upon the study design prior to performance of a full-scale research project.
The National Institute on Drug Abuse and Brain Solutions, LLC are paying for this study to be 
done. These funding sources will have no role in the study design, collection, analysis or 
interpretation of the data.
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 2 of 15
Subject Identification
Drs. Evins and Gilman, investigators on this study, are developing the technology that is used in 
this study for a potential method for detecting cannabis intoxication. Drs. Evins and Gilman have 
a financial interest in Brain Solutions, the company that is sponsoring this study. Drs. Evins, 
Gilman, Brain Solutions, and the hospital may benefit financially if this study shows that the 
technology is valuable. The hospital’s conflict of interest policies are handled by the hospital’s 
owner, Partners HealthCare. In accordance with these policies, Partners has determined that the 
interests create no significant risk to the welfare of participants in this study or to the integrity of 
the research. If you want more information about this, please contact the Partners Office for 
Interactions with Industry at PHSOII@partners.org, 857-282-2024. 
How long will I take part in this research study?
This phase of the study consists of four visits at MGH, at least 1 week apart, plus a screening 
visit to determine whether you are eligible for the study. At each study visit, you will be asked to 
arrive at an MGH inpatient unit or Center for Addiction Medicine at MGH the morning of your 
study visit. You will be given a standard breakfast, and then we will start the study procedures. 
You will be given either a physician determined dose of dronabinol or a placebo. Dronabinol is a 
capsule that has the psychoactive ingredient in marijuana. You will also receive a physician-
determined dose of ethanol or placebo ethanol. Ethanol is the primary constitute of alcoholic 
beverages. A placebo is an inactive substance, which does not contain medication and looks like 
the active study drug. For research to be good, it is important that you do not know whether you 
have been given the active study drug, Dronabinol, or the placebo, the pretend medicine. You 
will also not know if you have been given ethanol or placebo ethanol. This is one of the best 
ways we have to study the effects of marijuana and alcohol on the brain. It will take you about 7 
hours to complete each study visit. The 7 hours includes interviews, questionnaires, and the brain 
imaging assessments. You will have breaks for snacks and drinks in between testing periods. 
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. Please see below for details on texting. During the 
study, we will ask you to:

Fill out questionnaires

Answer questions about your medical and psychiatric health

Provide a urine sample to check for illegal drug use and pregnancy (in females)
- This urine drug screen test result will not become part of your medical record
- This pregnancy test result will not become part of your medical record
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 3 of 15
Subject Identification

Take a dronabinol capsule, which may contain THC, the psychoactive ingredient in 
marijuana

Consume a beverage that may contain ethanol, which is the primary constitute of 
alcoholic beverages. 

Participate in cognitive testing while your brain function is measured using a technology 
called functional near-infrared spectroscopy (fNIRS).

Complete a computer game that simulates driving

Complete a brief evaluation to assess your level of impairment
Texting:
Text messages by mobile/cell phones are a common form of communication. The fNIRS 
research study involves sending you text messages that are relevant to the research study.    
Texting over mobile/cell phones carries security risks because text messages to mobile/cell 
phones are not encrypted.  This means that information you send or receive by text message 
could be intercepted or viewed by an unintended recipient, or by your mobile/cell phone provider 
or carrier. 
Below are some important points about texting in this research study. 

Text messages are not encrypted, and therefore carry security risks. This research study and 
Partners Healthcare are not responsible for any interception of messages sent through 
unencrypted text message communications.  

You will be responsible for all fees charged by your carrier’s service plan for text 
messaging.  This research study and Partners Healthcare are not responsible for any 
increased charges, data usage against plan limits or changes to data fees from the 
research texts 

Text messages will only be read during regular business hours. The texting service can only 
interpret the number 1 to confirm the appointment or 3 to reschedule the appointment. If 
you need to send alternative messages, please communicate over email. 

Text messaging should not be used in case of an emergency.  If you experience a medical 
emergency, call 911 or go to the nearest hospital emergency department.  

You may decide to not send or receive text messages with staff associated with this research 
study at any time. You can do this in person or by sending the research email a message that 
says “Stop Research Text.” 

Your agreement applies to this research study only.  Agreeing to other texts from Partners 
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 4 of 15
Subject Identification
Healthcare, for example appointment reminders, is a separate process.  Opting out of other 
texts from Partners Healthcare is a separate process as well.

It is your responsibility to update your mobile/cell phone number with this research study in 
the event of a change.
Do we have your permission to send you text reminders to your cell phone?
  YES
 NO
Initials_________________
Screening Visit: Before conducting any study procedures, we will ask you to come in for a 
screening visit where we will determine if you are a good fit for this study. In this screening visit, 
you will review your medical history with a physician or registered nurse. We will also train you 
on some computer games.
Study Visits: If you are eligible for the study, we will ask you to attend four visits at the 
Translational and Clinical Research Center (TCRC) at Massachusetts General Hospital or Center 
for Addiction Medicine (CAM) at 101 Merrimac Street. You will arrive around 7:30am and 
complete the following procedures at your visits: 
Questionnaires:
First, you will fill out questionnaires that ask you about your personality, mood, and drug and 
alcohol use. Two of these questionnaires will ask you about how you are feeling and whether 
you feel any effects of the dronabinol capsule and ethanol beverage. These questionnaires will be 
repeated throughout the study before you take the capsule and then every 20 minutes (before and 
after brain imaging) for the rest of the study.
Dronabinol Capsule:
You will be asked to take a capsule called dronabinol that contains synthetic THC, which is the 
main psychoactive compound in marijuana. Dronabinol is approved by the U.S. Food and Drug 
Administration (FDA), and is used for appetite stimulation in AIDS patients and to treat nausea 
and vomiting in patients receiving chemotherapy. Doses similar to the one you will be given 
produce symptoms of intoxication such as laughing, elation and subjective heightened 
awareness. This capsule will be given to you after the first round of questionnaires and fNIRS 
imaging. A timeline is specified below. 
You will receive either THC capsules or identical placebo on two separate study visits, 
randomized for order. This study is double-blind, placebo-controlled, random order cross-over 
study. This means that neither you nor the study doctor or study staff will know which study 
drug you have received. 
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 5 of 15
Subject Identification
Because Dronabinol contains the psychoactive ingredient in marijuana, you are asked to refrain 
from using marijuana within 24 hours of the study visit. This is for your safety. If you have used 
marijuana within 24 hours, you may be asked to reschedule your study visit. 
Ethanol:
You will be asked to consume a beverage that may or may not contain ethanol, the primary 
chemical constituent in alcoholic beverages.  You will consume an amount of ethanol that is 
similar to that consumed by casual users of alcohol and is fairly low for moderate to heavy users.  
You will not be required to perform any physical tasks while intoxicated. Drinking alcohol under 
controlled laboratory conditions is unlikely to change current use patterns or cause addiction.
You will receive either ethanol or identical ethanol placebo on two separate study visits, 
randomized for order. This study is double-blind, placebo-controlled, random order cross-over 
study. This means that neither you nor the study doctor or study staff will know which beverage 
you have received. 
The alcohol administration procedure will take place approximately 45 min before the start of the 
second fNIRS session. We will take breathalyzer measurements approximately every 5-10 
minutes after the alcohol administration procedure. 
We ask that you refrain from consuming alcohol within 24 hours of all study visits, including the 
first one. This is for your safety. If you have consumed alcohol within 24 hours, you may be 
asked to reschedule your study visit.
Brain Imaging Assessment:
We will take pictures or images of your brain using an fNIRS machine. 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. Each fNIRS test will take about 30 minutes, and we will do testing at 
3 or 4 timepoints during the study visit. We will test everyone at 3 timepoints: before you take 
the capsule, at the peak of the capsule’s effects on the brain, and 1.5 hours after the peak brain 
effects, when most people will no longer feel the drug effects. Some people may still feel high or 
intoxicated during the third session of testing. If you still feel high or intoxicated, it may be 
necessary to repeat a 4th session of testing when you no longer feel the effects of the drug. We 
will use one of three approved devices: NIRSIT or NIRSport. Data from these devices will be 
analyzed in order to determine from which device we can yield the cleanest data (e.g. highest 
signal to noise ratio). 
The timeline of these procedures is as seen below. You will have breaks after each fNIRS 
session where you will be able to get food and drinks.
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 6 of 15
Subject Identification
Before beginning the first fNIRS scan, you will be seated comfortably in a chair and we will 
place a cap on your head. The cap holds the “optodes,” instruments that give off light and also 
receive and measure light. The cap is made of fabric and has velcro straps.  Because hair and 
scalp coloring might interfere with light measurements, we may need to adjust the cap after we 
put it on. We will keep checking until there is no interference. We will ask you to do some tasks. 
These tasks may consist of counting numbers, reciting words with a certain letter or in a certain 
category, or playing games on a computer that require you to make decisions about objects on 
the screen, such as the direction of arrows. If we can’t get a good signal with our equipment, then 
we will stop the procedure and take you out of the study. Once we get a good signal we will 
apply the different types of stimuli as described above. This will be performed in the dark 
because the fNIRS equipment is sensitive to all types of light. When the testing is over, the cap 
will be removed from your head.
Below is a photograph of the NIRS device and how it is worn.
Blood Draw: A nurse will draw about 1 mL of blood before you take the THC capsules and 
about every 40 minutes after you take the capsule, for about 3 hours. There will be a total of 10 
blood draws. Collected blood samples will be processed by an outside company for THC levels. 
Driving Simulation: We will use a computer-programmed driving simulator game to assess 
your motor coordination. This computer program simulates tasks that are relevant to driving 
using the keyboard, a foot pedal, and a joystick.
Pre-Dose:
fNIRS 
testing, 
interviews, 
vital signs, 
driving sim. 
refresher
Dronabinol
20 
min:
DEQ 
& 
BAES
, vital 
signs
40 
min:
DEQ 
& 
BAES
, vital 
signs
60 
min: 
ETOH,
DEQ & 
BAES, 
vital 
signs
80 
min:
DEQ 
& 
BAES
, vital 
signs
100 
min:
fNIRS, 
driving 
sim., 
field 
sobriety
280 min:
fNIRS, 
vital 
signs, 
discharge
Every 
20 
min:
DEQ & 
BAES, 
vital 
signs
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 7 of 15
Subject Identification
Information Storage
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. 
Your information may be kept for several decades.
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 study staff by phone 
at (617) 643-1984, or by email at fnirsstudy@partners.org. 
Disclosure of Results
Your individual research results will never be shared with you or entered into your medical 
record.
What are the risks and possible discomforts from being in this research 
study?
Risks of dronabinol: Dronabinol can increase your heart rate and/or result in bloodshot eyes. 
Some people experienced lowering in blood pressure, lightheadedness, fainting, falling upon 
abrupt standing, nausea, and vomiting. The likelihood that these problems may occur can be 
reduced by making sure you drink enough fluids. Dronabinol also has a reversible effect on 
appetite, mood, cognition, memory and perception. These effects are more pronounced at higher 
doses of dronabinol. They are also related to individual differences in how we break down 
(metabolize) the drug. In this study, we will use a high dose of dronabinol, so you may notice 
some of these effects. 
If there are any concerns that you are in need of clinical attention, the PI will be made aware of 
the issue immediately and will consult with a physician (co-investigator: A. 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 
appropriate for the situation. There is a licensed physician or registered, licensed nurse on site 
during your testing, and other MGH resources can be used as necessary.
An additional risk of participating in this study is that you may come up positive on a workplace 
drug screen as a result of taking a dronabinol capsule. If you choose, we can provide you with 
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 8 of 15
Subject Identification
documentation that describes the study procedures, and states that participation in this study will 
affect any drug screen results.
There is a paucity of data about the safety of administering dronabinol to pregnant women. Due 
to the possible risks to an embryo or fetus, or to an infant who is being breastfed, you will be 
excluded if you are currently breastfeeding or are/may become pregnant. 
You should not drive, operate machinery, or engage in any hazardous activity until you can 
perform such tasks safely. A member of our study staff will: (1) arrange cab service that has an 
approved partnership with MGH, and (2) will escort you to the cab at the end of the study visit. 
Alternatively, it would be acceptable for you to arrange travel home with a family member or 
friend. If you choose to do this, a study staff member will ensure that someone is there to bring 
you home prior to your departure.
In the investigators opinion, repeated exposure to dronabinol (two doses at least one week apart) 
does not involve increased risk to the adult participants who report using cannabis, often in much 
higher doses and of unknown purity, on a regular basis, often multiple times per day.
Risks of placebo: Placebo is a gelcap capsule filled with the same oil that is in Dronabinol, but 
without THC. There are no risks of taking a placebo capsule. 
Risks of alcohol: At low to moderate doses, ethanol can produce behavioral intoxication and 
physiological changes (feeling intoxicated, high, euphoric, dizzy, giddy, tired and lightheaded; 
increased heart rate, slurred speech, and slowed reaction time). You will consume an amount of 
alcohol that is similar to that consumed by casual users of alcohol and is fairly low for moderate 
to heavy users.  We will ask you to stay at the lab until your Breath Alcohol Content (BrAC) has 
fallen below 0.01. 
Risks of fNIRS: fNIRS is not considered to be risky. You are no more likely to be harmed than 
you are while performing everyday tasks. The system we will use in this study is a new 
experimental way to measure activity in the brain. No harmful effects have been reported so far, 
but it is possible that you may experience side effects that haven’t been reported yet. The light 
used is considered to be harmless – it is much less intense than the sunlight you would feel 
during an outdoor walk on a sunny day. It is possible that you may experience minor temporary 
skin irritation from the glue or tape which we use to attach the monitor and electrodes to the 
head.
We will not share your identity with anyone outside the Partners institutions. No record of your 
taking part or your results, from this research study will enter your medical records. However, 
we cannot guarantee your confidentiality.
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 9 of 15
Subject Identification
Risks of Blood draws: The discomfort associated with drawing blood by venipuncture (needle 
from a vein) is a slight pinch or pin prick when the sterile needle enters the skin. The risks 
include mild discomfort and/or a black and blue mark at the site of puncture. Less common risks 
include a small blood clot, infection or bleeding at the puncture site, and on rare occasions 
fainting during the procedure. Blood draws will be taken by trained nursing staff at the 
Translational and Clinical Research Center at Massachusetts General Hospital. Only a small 
amount of blood will be drawn, about one teaspoon.
What are the possible benefits from being in this research study?
You will not directly benefit from taking part in this research study. Researchers may benefit 
from what we learn in this research study. 
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 by check at the completion of the study for your participation. Your first visit is 
a screening and will last approximately 4 hours. You will be compensated $25 for this visit. Each 
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 10 of 15
Subject Identification
of the following study visits will take approximately 7 hours to complete. You’ll be paid $100 
for each of these visits. If you complete all aspects of the study, you’ll be given a $50 bonus. In 
total, you can earn up to $475 for your participation. You will also be provided transportation on 
the way home from the study visit, unless you decide to arrange a ride with a friend or family 
member. If you choose to do this, a study staff member will ensure that someone is there to bring 
you home prior to your departure. If you come in for the study but are found to be ineligible, you 
will be paid for the screening only ($20).
What will I have to pay for if I take part in this research study?
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.
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, Ph.D. 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 
would like to speak to a physician, you can call Dr. Eden Evins at 617-643-4679, Monday 
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 11 of 15
Subject Identification
through Friday 9AM to 5PM. If you need to speak to someone after office hours in an emergency 
you can call 617-726-2000 and ask the operator to page Dr. Evins. 
If you have questions about the scheduling of appointments or study visits, call our study staff at 
(617) 643-1984.
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: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 12 of 15
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.
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.   
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 13 of 15
Subject Identification
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.

I have had the chance to ask questions about texting with staff associated with this 
research study.  I have been informed of the risks and other information covered above 
and consent to the use of unencrypted text communications associated with this research 
study.
Study Information Included in Your Electronic Medical Record
A notation that you are taking part in this research study may be made in your electronic medical
record. Information from the research that relates to your general medical care may be included
in the record (for example: list of allergies, study medication). Following completion of the 
study, information pertaining to your involvement with the study will be removed from your 
medical record, including mention of study medication.
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 14 of 15
Subject Identification
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 (optional)
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 (optional)
Certificate of Confidentiality:
A federal Certificate of Confidentiality (Certificate) has been issued for this research 
to add special protection for information and specimens that may identify you. With a 
Certificate, unless you give permission (such as in this form) and except as described 
above, the researchers are not allowed to share your identifiable information or 
identifiable specimens, including for a court order or subpoena. Certain information 
from the research will be put into your medical record and will not be covered by the 
Certificate. This includes records of medical tests or procedures done at the hospitals 
and clinics, and information that treating health care providers may need to care for 
you. Please ask your study doctor if you have any questions about what information 
will be included in your medical record. Other researchers receiving your identifiable 
information or specimens are expected to comply with the privacy protections of the 
Certificate. The Certificate does not stop you from voluntarily releasing information 
about yourself or your participation in this study.
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  December 2008
Page 15 of 15
Subject Identification
Consent Form Version:  3/3/2020
Consent Form Title: fNIRS_consent2B_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 1 of 13
Subject Identification
Protocol Title: Using Imaging to Assess Effects of THC on Brain Activity 
(Phase 3)
Principal Investigator: Jodi Gilman, Ph.D.
Site Principal Investigator:      
Description of Subject Population: Healthy Adults ages 18-55
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.
Why is this research study being done?
The purpose of the study is to help us learn about the effects of marijuana on the brain. We hope 
to better understand certain brain regions that are important in decision-making and cognition, 
and how they are affected by marijuana intoxication. We are asking you to take part in this 
research study because you are a healthy adult between the ages of 18 and 55 who has used 
marijuana in the past. About 60 people will take part in this research study. This is a pilot study, 
which is a small scale preliminary study conducted in order to evaluate feasibility, time, cost, 
adverse events, and effect size (statistical variability) in an attempt to improve upon the study 
design prior to performance of a full-scale research project.
The National Institute on Drug Abuse and Brain Solutions, LLC are paying for this study to be 
done. These funding sources will have no role in the study design, collection, analysis or 
interpretation of the data.
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 2 of 13
Subject Identification
Drs. Evins and Gilman, investigators on this study, are developing the technology that is used in 
this study for a potential method for detecting cannabis intoxication. Drs. Evins and Gilman have 
a financial interest in Brain Solutions, the company that is sponsoring this study. Drs. Evins, 
Gilman, Brain Solutions, and the hospital may benefit financially if this study shows that the 
technology is valuable. The hospital’s conflict of interest policies are handled by the hospital’s 
owner, Partners HealthCare. In accordance with these policies, Partners has determined that the 
interests create no significant risk to the welfare of participants in this study or to the integrity of 
the research. If you want more information about this, please contact the Partners Office for 
Interactions with Industry at PHSOII@partners.org, 857-282-2024. 
How long will I take part in this research study?
This phase of the study consists of three visits at MGH, with at least 1 week between visits. At 
each visit, you will be given a different dose of dronabinol, which is a capsule that has the 
psychoactive ingredient in marijuana. It will take you about 6 hours to complete each study visit. 
The 6 hours includes interviews, questionnaires, and the brain imaging assessments. You will 
have breaks for snacks and drinks in between testing periods.
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. Please see below for details on texting. During the 
study, we will ask you to:

Fill out questionnaires

Answer questions about your medical and psychiatric health

Provide a urine sample to check for illegal drug use and pregnancy (in females)
- This urine drug screen test result will not become part of your medical record
- This pregnancy test result will not become part of your medical record

Take a dronabinol capsule, which has the psychoactive ingredient in marijuana

Participate in cognitive testing while your brain function is measured a technology called 
functional near-infrared spectroscopy (fNIRS).

Complete a computer game that simulates driving
Texting:
Text messages by mobile/cell phones are a common form of communication. The fNIRS 
research study involves sending you text messages that are relevant to the research study.    
Texting over mobile/cell phones carries security risks because text messages to mobile/cell 
phones are not encrypted.  This means that information you send or receive by text message 
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 3 of 13
Subject Identification
could be intercepted or viewed by an unintended recipient, or by your mobile/cell phone provider 
or carrier. 
Below are some important points about texting in this research study. 

Text messages are not encrypted, and therefore carry security risks. This research study and 
Partners Healthcare are not responsible for any interception of messages sent through 
unencrypted text message communications.  

You will be responsible for all fees charged by your carrier’s service plan for text 
messaging.  This research study and Partners Healthcare are not responsible for any 
increased charges, data usage against plan limits or changes to data fees from the 
research texts 

Text messages will only be read during regular business hours. The texting service can only 
interpret the number 1 to confirm the appointment or 3 to reschedule the appointment. If 
you need to send alternative messages, please communicate over email. 

Text messaging should not be used in case of an emergency.  If you experience a medical 
emergency, call 911 or go to the nearest hospital emergency department.  

You may decide to not send or receive text messages with staff associated with this research 
study at any time. You can do this in person or by sending the research email a message that 
says “Stop Research Text.” 

Your agreement applies to this research study only.  Agreeing to other texts from Partners 
Healthcare, for example appointment reminders, is a separate process.  Opting out of other 
texts from Partners Healthcare is a separate process as well.

It is your responsibility to update your mobile/cell phone number with this research study in 
the event of a change.
Do we have your permission to send you text reminders to your cell phone?
  YES
 NO
Initials_________________
Questionnaires:
First, you will fill out 10 questionnaires that ask you about your personality, mood, and drug and 
alcohol use. Two of these questionnaires will ask you about how you are feeling and whether 
you feel any effects of the dronabinol capsule. These questionnaires will be repeated throughout 
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 4 of 13
Subject Identification
the study before you take the capsule and then every 30 minutes (before and after brain imaging) 
for the rest of the study.
 
Dronabinol capsule:
You will be asked to take a capsule called dronabinol that contains synthetic THC, which is the 
main psychoactive compound in marijuana. Dronabinol is approved by the U.S. Food and Drug 
Administration (FDA), and is used for appetite stimulation in AIDS patients and to treat nausea 
and vomiting in patients receiving chemotherapy. Doses similar to the one you will be given 
produce symptoms of intoxication such as laughing, elation and subjective heightened 
awareness. This capsule will be given to you after the first round of questionnaires and fNIRS 
imaging. A timeline is specified below. 
You will be given different doses of dronabinol in each of the 3 study visits; a low dose, medium 
dose, and high dose. We cannot tell you until after the study which dose you were given at each 
visit, because knowing which dose you received may affect the way you feel. This study is a 
single-blinded study. This means you will not know which dose you have received, but the study 
doctor will know.
Because the drug contains the psychoactive ingredient in marijuana, you are asked to refrain 
from using marijuana within 24 hours of the study visit. This is for your safety. If you have used 
marijuana within 24 hours, you may be asked to reschedule your study visit. 
Brain Imaging Assessment:
We will take pictures or images of your brain using an fNIRS machine. 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. Each fNIRS test will take about 1 hour, and we will do testing at 3 or 
4 timepoints during the study visit. We will test everyone at 3 timepoints: before you take the 
capsule, at the peak of the capsule’s effects on the brain, and 1.5 hours after the peak brain 
effects, when most people will no longer feel the drug effects. Some people may still feel high or 
intoxicated during the third session of testing. If you still feel high or intoxicated, it may be 
necessary to repeat a 4th session of testing when you no longer feel the effects of the drug. We 
will use one of three approved devices: NIRSIT or NIRSport. Data from these devices will be 
analyzed in order to determine from which device we can yield the cleanest data (e.g. highest 
signal to noise ratio). 
The timeline of these procedures are as seen below. You will have breaks after each fNIRS 
session where you will be able to get food and drinks.
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 5 of 13
Subject Identification
Before beginning the first fNIRS scan, you will be seated comfortably in a chair and we will 
place a cap on your head. The cap holds the “optodes,” instruments that give off light and also 
receive and measure light. The cap is made of fabric and has velcro straps.  Because hair and 
scalp coloring might interfere with light measurements, we may need to adjust the cap after we 
put it on. We will keep checking until there is no interference. We will ask you to do some tasks. 
These tasks may consist of counting numbers, reciting words with a certain letter or in a certain 
category, or playing games on a computer that require you to make decisions about objects on 
the screen, such as the direction of arrows. If we can’t get a good signal with our equipment, then 
we will stop the procedure and take you out of the study. Once we get a good signal we will 
apply the different types of stimuli as described above. This will be performed in the dark 
because the fNIRS equipment is sensitive to all types of light. When the testing is over, the cap 
will be removed from your head.
Below is a photograph of the NIRS device and how it is worn.
Driving Simulation: We will use a computer-programmed driving simulator game to assess 
your motor coordination. This computer program simulates tasks that are relevant to driving 
using the keyboard, a foot pedal, and a joystick.
Information Storage
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. 
Your information may be kept for several decades.
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 6 of 13
Subject Identification
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 study staff by phone 
at (617) 643-7611, or by email at decisionmaking@partners.org. 
Disclosure of Results
Your individual research results will never be shared with you or entered into your medical 
record.
What are the risks and possible discomforts from being in this research 
study?
Risks of dronabinol: Dronabinol can increase your heart rate and/or result in bloodshot eyes. 
Some people experienced lowering in blood pressure, lightheadedness, fainting, falling upon 
abrupt standing, nausea, and vomiting. The likelihood that these problems may occur can be 
reduced by making sure you drink enough fluids. Dronabinol also has a reversible effect on 
appetite, mood, cognition, memory and perception. These effects are more pronounced at higher 
doses of dronabinol. They are also related to individual differences in how we break down 
(metabolize) the drug. In this study, we will use a high dose of dronabinol, so you may notice 
some of these effects. 
If there are any concerns that you are in need of clinical attention, the PI will be made aware of 
the issue immediately and will consult with a physician (co-investigator: A. 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 
appropriate for the situation. There is a licensed physician on site during your testing, and other 
MGH resources can be used as necessary.
An additional risk of participating in this study is that you may come up positive on a workplace 
drug screen as a result of taking a dronabinol capsule. If you choose, we can provide you with 
documentation that describes the study procedures, and states that participation in this study will 
affect any drug screen results.
There is paucity of data about the safety of administering dronabinol to pregnant women. Due to 
the possible risks to an embryo or fetus, or to an infant who is being breastfed, you will be 
excluded if you are currently breastfeeding or are/may become pregnant. 
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 7 of 13
Subject Identification
You should not drive, operate machinery, or engage in any hazardous activity until you can 
perform such tasks safety. A member of our study staff will: (1) arrange cab service that has an 
approved partnership with MGH, and (2) will escort you to the cab at the end of the study visit. 
Alternatively, it would be acceptable for you to arrange travel home with a family member or 
friend. If you choose to do this, a study staff member will ensure that someone is there to bring 
you home prior to your departure.
In the investigators opinion, repeated exposure to dronabinol (two doses at least one week apart) 
does not involve increased risk to the adult participants who report using cannabis, often in much 
higher doses and of unknown purity, on a regular basis, often multiple times per day.
Risks of fNIRS: fNIRS is not considered to be risky. You are no more likely to be harmed than 
you are while performing everyday tasks. The system we will use in this study is a new 
experimental way to measure activity in the brain. No harmful effects have been reported so far, 
but it is possible that you may experience side effects that haven’t been reported yet. The light 
used is considered to be harmless – it is much less intense than the sunlight you would feel 
during an outdoor walk on a sunny day. It is possible that you may experience minor temporary 
skin irritation from the glue or tape which we use to attach the monitor and electrodes to the 
head.
We will not share your identity with anyone outside the Partners institutions. No record of your 
taking part or your results, from this research study will enter your medical records. However, 
we cannot guarantee your confidentiality.
What are the possible benefits from being in this research study?
You will not directly benefit from taking part in this research study. Researchers may benefit 
from what we learn in this research study. 
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.
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 8 of 13
Subject Identification
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 by check at the completion of the study for your participation. You will be 
compensated $10 per hour of your time spent at each visit, plus an additional $30 for completion 
of the second fNIRS session, also at each study visit. Each study visit will take approximately 7 
hours to complete. This means that you can earn up to $300 in total if you participate in all three 
study visits. You will also be provided transportation on the way home from the study visit, 
unless you decide to arrange a ride with a friend or family member. If you choose to do this, a 
study staff member will ensure that someone is there to bring you home prior to your departure. 
If you come in for the study but are found to be ineligible, you will be paid for the screening only 
($20).
What will I have to pay for if I take part in this research study?
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.
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.
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 9 of 13
Subject Identification
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, Ph.D. 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 
would like to speak to a physician, you can call Dr. Eden Evins at 617-643-4679,  Monday 
through Friday 9AM to 5PM. If you need to speak to someone after office hours in an emergency 
you can call 617-726-2000 and ask the operator to page Dr. Evins. 
If you have questions about the scheduling of appointments or study visits, call our study staff at 
(617) 643-7611.
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?
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 10 of 13
Subject Identification
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

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, 
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 11 of 13
Subject Identification
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.
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.
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 12 of 13
Subject Identification

I understand the information given to me.

I have had the chance to ask questions about texting with staff associated with this 
research study.  I have been informed of the risks and other information covered above 
and consent to the use of unencrypted text communications associated with this research 
study.
Study Information Included in Your Electronic Medical Record
A notation that you are taking part in this research study may be made in your electronic medical
record. Information from the research that relates to your general medical care may be included
in the record (for example: list of allergies, study medication). Following completion of the 
study, information pertaining to your involvement with the study will be removed from your 
medical record, including mention of study medication. 
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 (optional)
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 (optional)
Certificate of Confidentiality:
A federal Certificate of Confidentiality (Certificate) has been issued for this research 
to add special protection for information and specimens that may identify you. With a 
Certificate, unless you give permission (such as in this form) and except as described 
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022


Partners HealthCare System
Research Consent Form
General Template
Version Date:  October 2014
Page 13 of 13
Subject Identification
above, the researchers are not allowed to share your identifiable information or 
identifiable specimens, including for a court order or subpoena. Certain information 
from the research will be put into your medical record and will not be covered by the 
Certificate. This includes records of medical tests or procedures done at the hospitals 
and clinics, and information that treating health care providers may need to care for 
you. Please ask your study doctor if you have any questions about what information 
will be included in your medical record. Other researchers receiving your identifiable 
information or specimens are expected to comply with the privacy protections of the 
Certificate. The Certificate does not stop you from voluntarily releasing information 
about yourself or your participation in this study.
Consent Form Version:  3/3/2020
Consent Form Title: fNIRS_consent3_CLEAN_3.2.20
IRB Protocol No: 2015P001516
Sponsor Protocol No: Detailed Protocol_02122018
Consent Form Valid Date: 2/15/2022
IRB Amendment No: CR7/AME111
Sponsor Amendment No: N/A
Consent Form Expiration Date: 2/15/2023
IRB Amendment Approval Date: 2/15/2022