Clinical trial NCT04576507
Conditions: Cannabis Pain Tolerance Hyperalgesia
Sponsor: New York State Psychiatric Institute
Start date: 2021-06-01; Completion date: 2023-12-31
Enrollment: 10 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication. These patients tend to seek products that are low in delta-9-tetrahydrocannabinol (THC; the primary psychoactive, and thus intoxicating, component of cannabis), and high in cannabidiol (CBD), a cannabinoid that purportedly has therapeutic benefit for pain but does not produce intoxicating effects. However, there are few well-controlled human laboratory studies assessing the efficacy of high-CBD cannabis for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability.

The proposed randomized, within-subjects, placebo-controlled 16-day crossover inpatient human laboratory pilot study (N = 16 healthy cannabis users; 8 men, 8 women) will address important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) If repeated cannabis use can result in hyperalgesia; 2) If tolerance to the analgesic and abuse-related effects of cannabis develops and is reversible. Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS), and participants will smoke cannabis 3x/day. Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.

This protocol is currently suspended due to the NYSPI human subjects research pause and results cannot currently be analyzed and posted. Upon un-suspension, we will analyze the data and post results immediately.

Detailed description:

Arms: arm 1: On the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A; 75% of active cannabis cigarette, 2.98% THC, 4.91% CBD) of cannabis. arm 2: Days 2-8 comprises the Placebo phase, in which a second strength (Dose B; 75% of one placebo cannabis cigarette, \<0.01% THC, CBD) of cannabis will be administered 3x/day. arm 3: Days 9-15 comprise the Active Phase, cannabis Dose A (75% of one active cannabis cigarette, 2.98% THC, 4.91% CBD) will be administered once again, 3x/day.
Interventions: intervention 1: Active Cannabis intervention 2: Placebo Cannabis
Intervention descriptions: intervention 1: 2.98% THC:4.91% CBD cannabis. intervention 2: \<0.01% THC:CBD cannabis.

Protocol documents:
Prot_000.pdf: 
Title: Repeated Cannabis Administration on Experimental Pain and Abuse Liability 
 
NCT: 04576507 
 
Document date: April 14, 2025 
 
IRB Approval date: February 10, 2025  
 


Use this form to detail study procedures.
Data Entry
Study Basics
  
If you are a user with a dual role of IRB Member and PI (for your own research),
there are two options when using the "Add a Note" feature:
selection of "Internal Only" (display note to IRB Members and Administrative Staff
only)--Use when acting as a Board Member
deselection of "Internal Only" (display note to study team)--Use when acting as a
PI
Submitter
Samantha Chong, BA
Email: Samantha.Chong@nyspi.columbia.edu
Business: (646) 774-6108
Indicate whether you are an OMH research team submitting to the NKI IRB as part of your
regular submission process (i.e., NKI IRB is your designated IRB of Record), or a NYSPI team
submitting to the NKI IRB. 
If you are an investigator from an OMH Psychiatric Center, you should select "OMH for NKI
Review".
If you are a NYSPI investigator applying for NYSPI IRB review, please select "NYSPI for NYSPI
Review (Determination request only (i.e NR and NHSR).
If you have questions regarding which designation is correct, please contact the NKI IRB at 845-398-2199,
nki-irb@nki.rfmh.org
NYSPI for NKI Review
Transfer Type
☐ Transfer
☑ Transfer with Modifications
☐ Not a Transfer
Submission Type
If you are transferring data you must select "Modification Form" for the Submission Type below. 
If you are trying to submit a request for determination of research select "New Study Application".
If you are selecting "Personnel Changes ONLY Modification Form", this is only used for addition of
OMH/OPWDD/NYSPI affiliated personnel, and removal of personnel with ANY affiliation.
☑ Modification Form
☐ New Study Application
☐ Personnel Changes ONLY Modification Form
 Main Location Output
NYSPI - New York State Psychiatric Institute
View xForm - IRB Protocol Form


Is this a Modification to Restart? (i.e., are you submitting your letter signed by the IO to lift the
Pause on your study?)
No answer provided.
IMPORTANT INFORMATION FOR STUDY TRANSFERS:
You have selected that this is either a “transfer”, or “transfer with modifications”. In the following
sections, you will be asked to update the study PI (on this page) and all personnel associated with your
study (on the next page).
The Personnel section should indicate all personnel that are currently approved and listed in your IRBNet
personnel form. You will need to add each currently approved person to the table below and indicate their
role on the study team.
If you selected “transfer” and wish to either add or remove personnel to your currently approved study,
please go back and select “transfer with modifications”. If you have selected “transfer with modifications”
you will be able to add new personnel or remove personnel from your approved study in addition to any
other changes you may wish to include.
Current Principal Investigator
Caroline Arout, PhD
Expirations: Good Clinical Practice -
01/08/2125 • 
NKI and NYSPI GCP Training -
01/08/2125 • 
NKI and NYSPI IRB Training -
07/06/2026
CV/Resume: Yes
Principal Investigator
Please type the Principal Investigator's name or email address.
If there is no result for the contact you are attempting to add, submit a New Contact Form to add this
person to the system. 
Caroline Arout, PhD
Email: caroline.arout@nyspi.columbia.edu
Phone:  
CV/Resume on file:
Yes
Is the PI a Student Researcher?
No
Is the PI an OMH/RFMH/OPWDD Employee?
Yes
Is this modification related to a change in PI?
No
Study Coordinator (if applicable)
Individuals should be listed here who are not part of study personnel but are responsible for coordinating
study documents within the OneAegis System. If this does not apply leave blank.  
No answer provided.
Title of Project
Effects of Repeated High-Cannabidiol Cannabis Administration on Experimental Pain and Abuse Liability in
Humans
Form Identifier
Modification Form - Caroline Arout, PhD


IRB Number
8016
This document is required for all research conducted at, or by researchers affiliated with, the
Office of Mental Health for which the Nathan Kline Institute reviews research. If your study is a
sponsored protocol, some of these sections may be detailed in the protocol provided by your
sponsor. Please submit a copy of the Sponsor’s Protocol. In this document you may provide the
page number, version date, and the version number of the Sponsor’s Protocol that is being
referenced.
Modification Description
List Requested Changes
This information will be displayed in your approval letter. Please be concise.
Multiple updates are being made in this form to supplement the original approved protocol for clarity and
completeness.
Please provide a justification for each change.
The original protocol was missing some of the elements required by the Nathan Kline Institute IRB. This
form includes the updates to supplement the overall transfer of the study, which will be reviewed along
with the Continuing Review lifecycle action, so that the study may be reviewed as a new submission to
the new IRB of Record (NKI).
Does any change increase the risk to study subjects?
No
Please indicate the current study status.
☐ Enrollment Open; Study Procedures Ongoing
☐ Enrollment Closed; Study Procedures Ongoing
☐ Study Open for Long-Term Follow-up Only
☑ Study Open for Data Analysis Only
Do any of the changes require updates to the consent document or the consent process?
No
List the documents included with this modification to request this change:
1. Continuing Review coversheet 
Study Personnel


Current Study Personnel
Name
Role
NKI and NYSPI GCP
Training
NKI and NYSPI IRB
Training
Alexis Marshall,
Research Assistant
06/20/2123
06/20/2026
Caroline Alleyne,
Research Assistant
07/10/2123
12/15/2026
Caroline Arout, PhD
Co-PI
01/08/2125
07/06/2026
Caroline Arout, PhD
Principal
Investigator
01/08/2125
07/06/2026
Eric Parmon, MD
Co-Investigator
06/12/2122
06/12/2025
Felipe Castillo, MD
Co-Investigator
11/15/2124
01/29/2028
Jeanne Manubay,
MD
Co-Investigator
07/14/2123
08/13/2025
Margaret Haney,
PhD
Co-Investigator
01/09/2125
01/10/2028
Richard Foltin, PhD
Co-Investigator
12/12/2122
08/26/2027
Stephanie Reed,
Ph.D.
Co-Investigator
11/09/2124
11/09/2027
Personnel do not need to be listed here if all of the following conditions are met:
They do not have access to any identifiers
They do not consent or interact with subjects
They are not listed on the Study Grant
For more information, please refer to the NKI Personnel Policy.
Anyone who is ONLY obtaining consent should be entered into the table below with the Role
"Obtaining Informed Consent". 
You have selected that this is either a “transfer”, or “transfer with modifications”. In the
following section, you will be asked to update all personnel associated with your study. This
section should indicate all personnel that are currently approved and listed in your IRBNet
personnel form. You will need to add each currently approved person to the table below and
indicate their role on the study team.  If you selected “transfer” and wish to either add or
remove personnel to your currently approved study, please go back and select “transfer with
modifications”. If you have selected “transfer with modifications” you will be able to add new
personnel or remove personnel from your approved study in addition to any other changes you
may wish to include.


Personnel Supplement
 1. Click "save" after each entry.
 2. To view linked CITI training information, click "refresh" after personnel entry.
 3. If there is no result for the person you are attempting to add, submit a New Contact
Form to add this person to the system. 
 4. If the "CV/Resume on file" field indicates "yes" then a CV has been saved in that person's
profile and a CV is not required. If that field is blank, then the individual must add a CV to
their profile, or the submitter can attach a CV at the bottom of the card.
 
Name:
Margaret Haney, PhD
CV/ Resume on file: No answer provided.
Role: Co-Investigator
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: Yes
Assessing Subject Capacity: Yes
CV/Resume:
Margaret Haney CV 2024.pdf
Name:
Felipe Castillo, MD
CV/ Resume on file: No answer provided.
Role: Co-Investigator
Location: NYSPI
Status at Site (If OMH Site):
☐ Full Time Employee
☑ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: Yes
Assessing Subject Capacity: Yes
CV/Resume:
Felipe Castillo CV 2024.pdf
Name:
Richard Foltin, PhD
CV/ Resume on file: No answer provided.
Role: Co-Investigator
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: No
Assessing Subject Capacity: No
CV/Resume:
Richard Foltin CV 2024.pdf
Name:
Caroline Alleyne,
CV/ Resume on file: No answer provided.
Role: Research Assistant
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: No
Assessing Subject Capacity: No
CV/Resume:
Caroline Alleyne CV 2023-24-8 (2).pdf
Name:
Alexis Marshall,
CV/ Resume on file: No answer provided.
Role: Research Assistant
Name:
Jeanne Manubay, MD
CV/ Resume on file: No answer provided.
Role: Co-Investigator


Good Clinical Practice
Contact
Expires (as of 04/14/2025)
Alexis Marshall,
06/20/2123
Caroline Alleyne,
07/10/2123
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: No
Assessing Subject Capacity: No
CV/Resume:
Alexis Marshall_CV 2024.pdf
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: Yes
Assessing Subject Capacity: Yes
CV/Resume:
Jeanne Manubay CV 2024.pdf
Name:
Caroline Arout, PhD
CV/ Resume on file: Yes
Role: Co-PI
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: Yes
Assessing Subject Capacity: Yes
CV/Resume:
Arout CV_11.2024.pdf
Name:
Eric Parmon, MD
CV/ Resume on file: Yes
Role: Co-Investigator
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: Yes
Assessing Subject Capacity: Yes
CV/Resume:
Eric Parmon CV.pdf
Name:
Stephanie Reed, Ph.D.
CV/ Resume on file: No answer provided.
Role: Co-Investigator
Location: NYSPI
Status at Site (If OMH Site):
☑ Full Time Employee
☐ Part Time Employee
☐ Volunteer
Obtaining Informed Consent: Yes
Assessing Subject Capacity: No
CV/Resume:
Stephanie Reed-Collins CV


Contact
Expires (as of 04/14/2025)
Caroline Arout, PhD
01/08/2125
Eric Parmon, MD
06/12/2122
Felipe Castillo, MD
11/15/2124
Jeanne Manubay, MD
07/14/2123
Margaret Haney, PhD
01/09/2125
Richard Foltin, PhD
12/12/2122
Stephanie Reed, Ph.D.
11/09/2124
Basic CITI Training
Contact
Expires (as of 04/14/2025)
Alexis Marshall,
06/20/2026
Caroline Alleyne,
12/15/2026
Caroline Arout, PhD
07/06/2026
Eric Parmon, MD
06/12/2025
Felipe Castillo, MD
01/29/2028
Jeanne Manubay, MD
08/13/2025
Margaret Haney, PhD
01/10/2028
Richard Foltin, PhD
08/26/2027
Stephanie Reed, Ph.D.
11/09/2027
Personnel To Remove
Click "Remove Contact" below, then add the contact to be removed to the list in the pop up window.
No answer provided.
Location Supplement
Will you be conducting activities at more than one site?
No
Please check off all sites where your study will take place under the supervision of Office of
Mental Health investigator(s). This includes sites where research teams will physically conduct
research, review records, and/or conduct recruitment.
If you have only one location, please select that location. If multiple locations, indicate in any
order.
New York State Psychiatric Institute
Facility Director for Main Site
Joshua Gordon, MD
Email: joshua.gordon@nyspi.columbia.edu
Phone:  
Study Details


Describe the purpose of the investigation. If this is a clinical trial, this should include a
description of the disease and the goals of the research.
Chronic pain is a significant public health concern in the U.S., for which prescription opioids have
historically been the standard treatment. This has resulted in striking rates of opioid use disorders and
fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal
abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose.
More than 80% of medicinal cannabis users report pain as their primary medical indication. These
patients tend to seek products that are low in delta-9-tetrahydrocannabinol (THC; the primary
psychoactive, and thus intoxicating, component of cannabis), and high in cannabidiol (CBD), a
cannabinoid that purportedly has therapeutic benefit for pain but does not produce intoxicating effects
[1]. However, there are few well-controlled human laboratory studies assessing the efficacy of high-CBD
cannabis for pain in the context of abuse, and even less is known regarding the effects of daily repeated
use of cannabis on pain and its relationship to abuse liability. Carefully controlled research is needed. The
proposed randomized, within-subjects, placebo-controlled 16-day crossover inpatient human laboratory
pilot study (N = 16 healthy cannabis users; 8 men, 8 women) will address three important gaps in our
understanding of the potential therapeutic utility of cannabis for pain: 1) If abruptly switching active
cannabis(4.91% CBD/2.98% THC) to inactive cannabis (0% CBD/THC) increases experimental pain
sensitivity, i.e. hyperalgesia, relative to baseline and if these effects parallel measures of cannabis
withdrawal such as disrupted mood and sleep (Each cigarette contains approximately 39.28mg of CBD
and 23.84mg of THC. They smoke 75% of one cigarette, so each dose is approximately 29.46mg of CBD
and 17.88mg of THC); 2) If tolerance to the analgesic and abuse- related effects of cannabis is reversed
following 7 days of abstinence from active-THC cannabis (by administering 0% CBD/THC, inactive
cannabis); 3) If tolerance is present/develops to repeated, daily smoked cannabis (4.91% CBD/2.98%
THC) administration on measures of experimental pain and abuse liability. Two distinct modalities of
experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing
Thermal Temporal Summation (QST-TTS). The study will start with a day of active cannabis
administration (4.91% CBD/2.98% THC) given 3x/day in order to standardize cannabis exposure across
participants (Day 1), and will be followed by a 7-day “inactive phase” (Day 2-8) in which participants will
smoke inactive cannabis (0% CBD/THC) 3x/day during this 7-day period. The last 7 days (Day 9-15) will
comprise an “active cannabis phase” in which participants will smoke cannabis (4.91% CBD/2.98% THC)
3x/day. Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep
and subjective mood assessments. With rates of chronic pain increasing and limited availability of safe
and effective treatment alternatives to opioids, this study will provide essential data regarding the
efficacy of daily cannabis use on measures of analgesia and abuse liability and the consequences of
cannabis abstinence on measures of pain, as it is possible that abrupt cessation of cannabis use will lead
to worsened baseline pain.
General Overview:
This within-subjects study will examine the effects of daily repeated use of cannabis on pain and its
relationship to abuse liability. Healthy, non-treatment seeking cannabis smokers (N=16, 8M, 8F) will be
admitted to the research center on 5- South of NYSPI for a 16-day inpatient stay. On the first full
inpatient day, participants will smoke active cannabis (4.91% CBD/2.98% THC). Days 2-8 will comprise
the Inactive Phase, in which placebo cannabis (0%CBD/THC) will be administered 3x/day. The next 7
days (Day 9-15) will be the Active Phase, in which active cannabis (4.91% CBD/2.98% THC) will be
administered at the same time points (Table 1). Participants will complete subjective effects visual analog
scales and a cannabis rating form daily, and will complete the Cold-Pressor Test and Quantitative Sensory
Testing-Thermal Temporal Summation on Days 1, 2, 5, 8, 9, 12, and 15 to explore three critical questions
regarding cannabis’ therapeutic utility for pain (as illustrated in Figure 1): 1) If abruptly switching active
cannabis to inactive cannabis increases experimental pain sensitivity, i.e. hyperalgesia (Day 2-8; red
bars) relative to baseline and if these effects parallel measures of cannabis withdrawal such as disrupted
mood and sleep; 2) If pharmacological tolerance to the analgesic and abuse-related effects of cannabis is
reversed following 7 days of abstinence from active-THC cannabis (by administering 0% CBD/THC,
inactive cannabis): defined as a) significant decrease in CPT latencies and QST-TTS response following
active cannabis administration on Day 12 or Day 15 compared to Day 9 (Active Phase), and b) a
significant decrease in subjective visual analog scale ratings of abuse, i.e. ‘Good Drug Effect’ following
active cannabis administration on Day 12 or Day 15 (Active Phase) compared to Day 9 (Active Phase);
3)If tolerance is present/develops to repeated, daily smoked cannabis (4.91% CBD/2.98% THC)
administration on measures of experimental pain and abuse liability (green bar): defined as a significant
increase in CPT latencies and QSTTTS response and ‘good drug effect’ after active cannabis
administration when Day 9 of the Active Phase is compared to Day 1.


Provide the hypothesis for this research.
Aim 1. Determine the effects of abstinence from active cannabis (by use of 0% THC cannabis) on
experimental pain. We hypothesize that (a) abrupt abstinence will result in increased CPT and QST-TTS
responses, indicative of withdrawal-induced hyperalgesia.
Aim 2. Determine if a) tolerance is present (Day 1) and is reversed following abstinence from active
cannabis (Days 2-8); b) tolerance develops to daily smoked active cannabis (4.91% CBD/2.98% THC;
Days 9-15) administration on pain and abuse liability measures. We hypothesize that: (a) existing
analgesic tolerance will be reversed following abstinence from active cannabis; (b) over the course of the
active cannabis phase, tolerance will develop to cannabis’ analgesic but not abuse-related effects.
Include pertinent information about the relationship of the proposed research to previous
studies and describe the significance of the proposed research. Be brief.
In an attempt to mitigate the ongoing opioid crisis, the CDC and NIH have urged the identification of non-
opioid medications for chronic pain. Developing novel pain management approaches with lower abuse
liability than opioids is a public health necessity. In light of the widespread legalization of cannabinoids
(cannabis or components of the cannabis plant) across the U.S, use of these products is increasing both
recreationally and medicinally. Many medicinal cannabis users indicate that they use cannabinoid
products to assist with chronic pain management; of the >1.2 million registered medical cannabis
patients across the U.S., the majority (>80%) cite pain relief as the primary reason for use. These
legislative changes and use patterns are emerging in the absence of sufficient controlled scientific
evidence supporting efficacy for pain. Specifically, most people using cannabinoids for pain do so on a
daily and long-term basis, yet it is unknown how cannabinoid effects change with repeated use. Of the
100+ cannabinoids identified, the two major and most prominently used are delta9- tetrahydrocannabinol
(THC) and cannabidiol (CBD). THC is the primary psychoactive component of cannabis and has been
shown to exert analgesic effects by our laboratory (Cooper, 2013, p.1984), but its therapeutic utility
occurs at concentrations associated with abuse liability. CBD, on the other hand, is non-intoxicating thus
is not considered to have abuse liability. For this reason, products that are high in CBD content are being
used at increasing rates for various medical conditions ranging from childhood seizures (for which it is
FDA- approved as Epidiolex) to chronic pain.
A number of studies have shown combinations of CBD:THC to have analgesic efficacy and minimal abuse
liability in populations with chronic pain, including HIV-related neuropathic pain and cancer pain.
However, there is very little scientific evidence outside of medically-ill populations to support the
therapeutic utility of CBD:THC combinations for pain relief in the context of abuse liability, particularly
when used repeatedly. Further, while some studies suggest that CBD attenuates the adverse effects of
THC (Osborne, 2017, p.310-324) other studies have demonstrated the opposite (Solowij, 2019, p. 17-35)
or no effect at all (Haney, 2016, p. 1974-1982). Despite mixed evidence for efficacy and abuse potential,
people using cannabis medicinally often seek out products from dispensaries that are high in CBD and
low in THC content due to the widespread belief that these products offer therapeutic benefit without
abuse liability (Mead, 2017, p.288-291).
The consequences of daily use of combined smoked CBD:THC cannabis on pain outcomes or abuse-
related effects are not known. An additional unknown is how cessation of daily use affects measures of
pain. Cannabinoids can increase pain sensitivity at certain doses, but no studies have investigated if pain
sensitivity increases as a function of abrupt cannabis abstinence. It is possible that cannabis’ analgesic
effects diminish with repeated use, resulting in increased use to overcome pharmacological tolerance.
Further, abrupt cannabis cessation may result in hyperalgesia along with other symptoms of cannabis
withdrawal, which would make maintaining abstinence difficult. These factors could worsen ongoing pain
and increase the likelihood of developing cannabis use disorder. Finally, it is unknown if analgesic
tolerance can be reversed following a period of abstinence from active cannabis. Currently, there are no
data on these effects to inform patients using cannabis on a regular basis for pain.
Study Procedures


Research Procedures (Select all that apply):
☐Data Analysis/ Chart Review
☑Drug Study
☐Device Study
☐MRI w/ Contrast: MRIs for research purposes are subject to CBIN policy on Incidental Findings
☐MRI w/out Contrast: MRIs for research purposes are subject to CBIN policy on Incidental Findings
☑Interview/Survey/Questionnaire
☑Blood Collection
☑Sample Collection other than blood
☑Non Invasive Physical Measurements
☐Student Research
☐Ionizing Radiation
☐IV Infusion
☐Genetic Research
☐Transcranial Magnetic Stimulation (TMS)
☐Transcranial Direct-Current Stimulation (tDCS)
☐Requesting that NKI serve as the IRB for an institution outside of OMH/RFMH
☐Establishment of a Research Repository
Sample Collection Other Than Blood
☑Urine
☐Cerebral Spinal Fluid (CSF)
☑Other
Specify Other
COVID-19 nasopharyngeal swabs


Detail all questionnaires and assessments (including validated assessments) that will be used
for this study.  
These items can be explained or listed and attached. If the assessment or questionnaire is validated,
please confirm that there have been no modifications to the document. If the study instrument is not a
validated tool please attach the document with this submission.
Some assessments are conducted under a screening protocol (#7091R), while others are conducted
under the study protocol (#8016), which is indicated below.
Screening Assessments (these assessments (which are validated and not modified from their original
form) are conducted under screening protocol 7091R and are thus not part of protocol 8016, but are
detailed for clarity in our procedures):
1) Telephone Interview: 15 min.
2) Timeline Follow-Back Interview for substance use: 10 min.
3) Drug Use History Questionnaire: 10 min.
4) General Health Questionnaire: 5 min.
5) Medical History Questionnaire: 10 min.
6) Beck Depression Inventory: 5 min.
7) General Pain Index Questionnaire: 5 min.
8) Structured Clinical Interview for DSM-5: 30 min.
9) 12-lead electrocardiogram: 15 min.
10) Laboratory Tests (blood count with differential chemistry profile, liver enzymes, and GGTP): 30 min.
11) Urinalysis with 12-panel urine drug testing: 5 min.
12) Physical and Psychiatric Examination: 30 min, unless there is an indication for a diagnosis, in which
case it will be 90 min.
Experimental Assessments (conducted under protocol 8016):
1) The Cold Pressor Test (CPT) is a validated and reliable pain-induction procedure that reflects A-delta
nerve fiber
activity within the autonomic nervous system and closely mimics clinical chronic pain. CPT has been
shown to have
excellent reliability and predictive validity for medication-induced analgesia, including cannabinoids. For
this task, two
temperature- controlled circulating water baths maintain warm (36.5-37.5ºC) and cold (3.5-4.5ºC) water.
Participants
immerse their hand into a warm bath for 3 min (to standardize baseline skin temperature), then the cold
bath, indicating when they first experience pain and withdrawing when the pain gets uncomfortable.
Study staff will record time (in seconds) until participants: 1) report discomfort (pain threshold), and 2)
withdraw their hand from the cold water (pain tolerance): 15 min.
2) Quantitative Sensory Testing-Thermal Temporal Summation (QST-TTS) uses repetitive fixed frequency
and intensity
heat stimulation to induce central sensitization of C-fibers in the spinal cord and is regarded as an
experimental
correlate of the ‘wind-up’ phenomenon in the dorsal horn. As dorsal horn CB-1 activity has been linked to
suppression of ‘wind-up’ and central sensitization (the mechanism purportedly underlying cannabis’
efficacy for neuropathic pain),
cannabis use may decrease QST-TTS response, mirroring analgesia on the CPT during active cannabis
administration vs. placebo. For this task, a Medoc TSA-II NeuroSensory Analyzer with a 30 x 30 mm
Peltier thermode applies tonic noxious heat stimulation to the thenar eminence of the palm: the baseline
temperature is 32.0°C, increases at a rate of 1°C/s up to 46.5°C, and remains constant for 120 sec. Total
duration: 3 min.
3) Cold Pressor Test Visual Analog Scale (CPT-VAS): 11-item questionnaire rating the physiological and
subjective effects of the cold water on a 100 mm VAS after the CPT: 15 sec.
4) Quantitative Sensory Testing-Thermal Temporal Summation Computerized Visual Analog Scale
(CoVAS): Participants
rate magnitude of perceived pain on a 100 mm VAS during the QST-TTS: 135 sec.
5) Physiological response to pain: Heart rate and blood pressure will be measured throughout pain
assessments: 2 min.
6) Pain Intensity/Bothersomeness Scale (PIBS): Ratings of CPT and QST pain on a 0-to-10 scale: 0 being
‘not
painful/bothersome at all’ and 10 being ‘most painful/bothersome feeling imaginable’: 10 sec.
7) Subjective Effects: A series of 100 mm VAS in which participants indicate how they are feeling at that


moment will be completed 3x/day. The 44-item VAS includes mood, physical symptom, and drug effect
descriptors. Based on a cluster analysis, we employed arithmetic means of individual item scores to
reduce 34 of the 44 items into eight subscales: good drug effect; miserable; irritable; anxious; bad
effect; social; and confused. We also analyze individual VAS drug craving ratings. These subjective
measures may detect changes in abuse-related effects as well as changes in mood (miserable, irritable,
anxious, cannabis craving) as a function of cannabis condition: 3 min.
8) Objective Sleep Measures: Participants will wear an Actiwatch Activity Monitoring System that tracks
gross motor
activity (Actiwatch®: Respironics Company, Bend, OR) and records objective sleep outcomes (hours
slept, number of
awakenings). We have used this system effectively to demonstrate perturbations in sleep as a function of
cannabis
withdrawal.
9) Sleep Questionnaire: Participants will complete a sleep questionnaire which consists of a 7-item, 100
mm VAS
instrument that assesses the quality of sleep and how many hours slept the previous night and
wakefulness in the
morning. Participants will be asked to rate symptoms by placing a mark on a line representing a
continuum from “not at all” (on the left of the line) to “extremely” (on the right of the line) indicating how
the phrase relates to the last night’s sleep: 30 sec.
10) Cannabis Rating Form (CRF): Participants rate the strength, liking, desire to take again, good drug
effect and bad
drug effect of cannabis on a 100mm VAS: 2 min.
Please attach all Questionnaires and Assessments listed above.
No answer provided.


Describe the procedures in sufficient detail so that a reviewer, who is not familiar with them,
can comprehend what is to be done and can evaluate any risks.
This study is now in data analysis only, and the following procedures describe the study as it was
approved and conducted during the COVID era.
Consent Procedures:
Step 1 (conducted under #7091R). After initial determinations of eligibility (e.g. current drug use
patterns, attitude about treatment) obtained via the telephone interview, volunteers will be emailed a
secure link to a Qualtrics survey containing assessments regarding demographic and medical information,
thereby eliminating the need for subjects to travel to NYSPI to complete these questionnaires and thus
reducing their risk of exposure to COVID-19 by traveling to the institution or while on site. They will be
asked to review our screening and evaluation consent form (IRB #7091R), as well as the study consent
form, HIPAA form and NYSPI privacy practices. Copies of the study consent form and the HIPAA form will
be sent to participants via encrypted email. Participants will be required to select YES/NO to indicate
whether they reviewed these documents and agree to complete the assessments before they may
continue.
Step 2 (conducted under #7091R). Interviews with a trained psychologist will occur via HIPAA-
compliant virtual telemedicine platforms such as Apple Facetime or Webex, once again minimizing the
risk of exposure to COVID-19 that would exist if requiring all subjects to travel to NYSPI for an in-person
interview. Psychologists (Drs. Arout, Haney, Kearney-Ramos, Harris) will conduct interviews regarding
drug use and psychiatric symptoms and will provide a detailed explanation of the procedures outlined in
the consent form. If the volunteers are eligible for continued screening after the PhD interview, they will
be invited fora single in-person screening visit to review the study consent form, complete medical
assessments, and be tested for COVID-19. A dated note-to-file will be included in the participant's chart
of the remote/verbal consent procedure documenting the consent discussion and review of the consent
form, along with the participant's electronic agreement of the consent, as signed by the consenter. 
Step 3 (conducted under #8016). During the single in-person screening visit, participants will review
and sign the study consent form after reviewing it with a study physician. Medical and psychiatric
interviews will be conducted by a physician in the Division on Substance Abuse (e.g. Drs. Castillo,
Manubay, Parmon), and will include a physical examination, nasal COVID-19 test, and review of medical
results and study inclusion/exclusion criteria. All of our psychiatrists have completed at least 4 years of
psychiatric training and most are Board Certified (those not Board Certified are in the process of
obtaining certification). Physicians will determine whether volunteers have current Axis I psychopathology
(e.g. major depressive episode, bipolar disorder, schizophrenia) requiring medical intervention. The
physicians discuss this protocol with the volunteers and document their consent to the research study. No
study procedures will begin until the physician verifies the participant meets inclusion/exclusion criteria,
understands the medical risks of participation, and is capable of providing informed consent. Dr.
Manubay, the senior study physician, will settle any disagreements among the study team as to a
volunteer's eligibility, and will make the final decision as to study participation. All procedures are
consistent with the Division of Substance Abuse Guidelines for Investigators (9/8/08). Research staff will
perform laboratory tests (ECG, blood draw, urinalysis) for medical screening with study physicians.
Psychologists will sign the study consent form after volunteers complete medical and further psychiatric
evaluation with study physicians. Thus, several interviews in which drug use is proved will be conducted
with volunteers prior to telling them the nature of the study. In this way, we minimize the probability that
they will misrepresent their drug use in order to gain entry into the research. Volunteers expressing
interest in treatment at any point during participation will be given an immediate treatment referral.
Step 4 (conducted under #8016). Following the physical and consent, volunteers will re-read the
study consent form and procedures with study personnel, practice study tasks, and complete a multiple
choice consent quiz that covers pertinent study procedures. This multi-consent process provides
participants with new information at each decision point. Volunteers will have spent time in the laboratory
engaging in the behaviors and tasks required for full study completion. These procedures provide fully
informed consent and will allow study personnel to accurately determine a volunteer's capacity to provide
fully informed consent. 
Study participants are informed of the risk of exposure to COVID-19 while traveling to our facility and
while completing research activities on site, as well as all safety guidelines enacted by NYSPI, during the
initial phone interview with research  staff, the PhD interview, and during the consent discussion
conducted with a physician during their physical examination. Thus, this new risk and ways to minimize
this risk are communicated to study participants at each step in the screening process. Participants will
always be given the option to reschedule their visit to our facility if they do not feel comfortable traveling
to their appointment (for example the subway is too crowded). This will be noted as part of the consent
procedures.
Laboratory Facility. All cannabis administration time-points and tasks will be conducted in the
Substance Use Research Center (SURC) located on the 3rd floor of the NYS Psychiatric Institute. The
time-points and tasks described in this protocol will be conducted in the Outpatient Cannabis Laboratory.
The laboratory has two testing rooms that are adjacent to a control room. The testing rooms are
equipped with a workstation consisting of a worktable, a comfortable chair, and a Macintosh computer


networked with computers located in the adjacent control room used to collect subjective-effects data.
The test rooms are also equipped with automatic sphygmomanometers, electrocardiography systems,
CPT apparatus, a mini refrigerator, and microwave. The control room oversees the test rooms via a one-
way mirror. It contains office and storage space and Macintosh computer systems with a Hewlett Packard
Laser Jet printer. Macintosh computers in the control room are used to run sessions and to automate data
collection. Participants are continuously monitored through one-way glass and are able to communicate
with the investigators via an intercom. The control room also houses ancillary computer equipment and
physiological monitoring equipment (heart rate, blood pressure monitor, pulse oximeter unit). Participants
will sit in a comfortable task chair in front of a Macintosh computer. A response manipulandum (“mouse”)
will be used for completion of pain rating scales and subjective-effects questionnaires.
Screening Process: (also see details under Consent Procedures regarding remote procedures).
Eligibility screening for this study will be conducted under IRB protocol 7091R. As described in the 7091R
protocol, the screening process will consist of:
1) several self-report questionnaires and 2) several structured clinical interviews conducted remotely and
on the in person screening visit, participants will have 3) vital signs, height and weight, 4) urine and
blood samples for routine laboratory tests and drug screening, a nasal swab test for COVID-19, 5) an
ECG, and (6) a physical examination. Drug interviews, psychological and general assessments related to
study issues will be conducted by PhDs who have had extensive experience in these procedures. All of
these procedures will be done under protocol #7091R. Participants deemed eligible for further screening
after the PhD interview will be invited to come to the laboratory for an in-person visit, during which they
will sign the Screening Consent Form under IRB protocol 7091R (before proceeding with additional
screening procedures).
Training Session: All potential participants who meet inclusion/exclusion criteria will undergo a training
session on the CPT and QST-TTS prior to admission into the study, since there is a proportion of the
population that is unable or unwilling to tolerate pain induced by the CPT and/or the QST-TTS.
Cold Pressor Test: The CPT apparatus consists of two refrigerated circulators, filled with warm (36.5-
37.5°C) and cold (3.5- 4.5°C) water. At the beginning of the procedure, a research assistant (same
gender as the participant) will read a script describing the procedure to the participant, as well as take
their blood pressure and heart rate as a safety assessment and for baseline values. Participants will then
insert their non- dominant hand into the warm water and remove it after 3 minutes; skin temperature of
the thumb pad will be measured. Blood pressure and heart rate will be taken halfway through the 3-
minute period in the warm water tank. Participants will then insert their hand in the cold water and will
be instructed to report when they first experience pain (pain threshold) and remove their hand when the
cold water can no longer be tolerated (pain tolerance). Maximum immersion time will be 3 minutes.
Immediately after hand removal, blood pressure, heart rate, and skin temperature will be measured.
Participants will then complete measures of CPT-induced discomfort (described below). Individuals who
do not report pain and/or do not remove their hand within 3 minutes will be excluded. If at any point that
vitals are taken systolic pressure is greater than or equal to 180, diastolic pressure is greater than or
equal to 110 (each measure monitored and confirmed by a manual reading), in which either is sustained
after a manual redo for more than 120 seconds, will result in suspending the CPT for that participant for
that given day. If a single reading of systolic blood pressure is greater than 200, or a single reading of
diastolic blood pressure is greater than 120 (each measure confirmed by a manual reading), or a
confirmed heart rate greater than 160, the CPT session will be immediately suspended for the participant
that given day. Additionally, for either parameter, the participant’s vital signs will be assessed every thirty
minutes until it stabilizes within normal range under the guidance of the study physician. In the event
that vital signs are not stabilized, we will assess the participant as described in the Criteria for Early
Discontinuation section.
 
Quantitative Sensory Testing-Thermal Temporal Summation. The QST-TTS apparatus is a thermal
testing analyzer with a 30 x 30 mm Peltier thermode, which will use repetitive nociceptive heat
stimulation of a fixed frequency and intensity. At the beginning of the procedure, a research assistant
(same gender as the participant) will read a script describing the procedure to the participant. Tonic
noxious heat stimulation will be applied to the palm using a ramp-and-hold method,  in which the
baseline temperature will be set at 32.0°C, and will increase at a rate of 1°C/s up to 46.5°C, remaining
constant for 120 sec. During the total duration of stimulation (135 seconds), participants will
continuously rate the magnitude of perceived pain (described below). Individuals experiencing
neurosensory deficits will be excluded.
Inpatient Phase (Table 2; attached)
Day -1 Check-In Procedures. Eligible participants will be admitted into the 5-South inpatient unit.
Although we will have open enrollment, we aim to maximize enrollment of up to three participants on the
move-in day, or as many as the 5th floor can accommodate at that time. Move-in procedures will include
a non-invasive strip search, a urine drug screen test, a urine pregnancy test for women, vital signs
(sitting blood pressure and heart rate), weight, breathalyzer test for ethyl alcohol (EtOH), a timeline
follow back interview, and verification of eligibility. Participants will be trained on computer tasks and
cannabis smoking procedures before data collection begins.


Days 1-15 Study Procedures
Participants will be awakened at approximately 0700h on study days and lights out each night at 2300h
by 5-South staff. At 0800h, participants will receive breakfast. At 0900h, participants will be bought down
to the third-floor outpatient room to have vital signs taken (seated blood pressure and pulse rate) and to
complete a sleep questionnaire, precannabis administration. Actiwatches will be put on both wrists each
night and will be collected each morning.
Day 1 (Standardization)
Since we will recruit moderate-heavy cannabis users with varied use patterns, they will enter the study
with varying pharmacological tolerance. Therefore, Study Day 1 will be an initial day of active cannabis
administration to standardize exposure to the same strength of smoked cannabis across participants prior
to enforced abstinence from active cannabis in the Inactive Phase (Day 2-8). Participants will be
administered active cannabis (two one 4.91% CBD/2.98% THC cigarettes) at 1000h, 1300h, and 1600h.
 
Days 2-8 (Inactive Phase)
On Study Days 2-8, participants will be administered one inactive cannabis cigarette (0.00% CBD/THC)
at the same three time-points (1000, 1300, 1600). We have shown that inactive cannabis controls for
expectancy effects of smoking, producing small but reliable increases in ratings of ‘high’ [5]. Therefore,
this phase will assess how abstinence from active- THC cannabis affects pain outcomes in parallel to
measures of cannabis intoxication and withdrawal (mood, sleep).
Days 9-15 (Active Phase)
On Study Days 9-15 participants will be administered an active cannabis cigarette (one 4.91%
CBD/2.98% THC cigarette) at the same three time-points (1000, 1300, 1600), with the exception of Day
15 where they will be administered active cannabis only at 1000. This phase will allow us to see if CPT
and QST pain outcomes and abuse liability change over time
Move Out
Following completion of all assessments of Day 15, the PI will discuss with the participants benefits of
cannabis
cessation, highlighting availability of a range of treatment options, prior to discharge. At 180 minutes
post-cannabis administration, participants will complete field sobriety tests, vital signs, and a Mini-
Mental State Exam (MMSE), and will be permitted to leave once they meet discharge criteria. Criteria for
discharge will be met when participants report no ongoing subjective drug effects and have no signs of
impairment or intoxication, pass the field sobriety test, have normal vitals, and a normal mental status
score as assessed by the MMSE. Dr. Arout, Haney, or Kearney-Ramos will make the final determination
that the patient is sober and medically stable and can leave the facility. 
The effects of smoked cannabis are typically gone within 3 hours. In the rare event that a participant is
still impaired at the conclusion of Study Day 15, they will be asked to remain in the laboratory until the
effects wear off, and will be paid extra (i.e., $10 per hour for any additional time they remain in the
laboratory). Participants may be sent home in a taxi, for which they will be reimbursed. They will be
allowed to leave the facility when they pass the field sobriety test and are medically stable. They will be
instructed not to drive a car or use other drugs or alcohol for 8 hours after administration of cannabis;
therefore, participants will be required to take public transportation (i.e., bus or subway) from the
laboratory on Day 15, for which they will be reimbursed (included in their pay for Day 15). 
CPT and QST-TTS
On Days 1, 2, 5, 8, 9, 12, and 15, participants will complete the CPT and QST-TTS pain tasks 30 minutes
before the 1000h cannabis administration (baseline), and 0, 15, 30, 45, 60, and 90 minutes post-
cannabis administration. Participants will also complete measures of CPT-induced discomfort (CPT-VAS,
PIBS) and will continuously rate the magnitude of perceived pain for the temporal heat stimulation of the
QST-TTS (Co-VAS) at these time-points. On these days of pain testing, except for Day 15, participants
will also complete a cannabis rating form and subjective effects visual analog scales pre-cannabis
administration (0945h), for a full-time course after the first cannabis administration (1015h, 1045h,
1115h, 1145h, 1215h), and after each subsequent cannabis administration timepoint (1315h, 1615h). On
Day 15, these assessments will conclude with the 1215 time-point. Vital signs will be taken before and
after each pain assessment. In addition, vital signs will be taken halfway through the duration of each
CPT assessment. If vital sign parameters are exceeded at any point during the CPT task, staff will follow
the same assessment procedures as stated in the training section above.
On days when there are no pain assessments, participants will complete just the cannabis rating form
and subjective effects battery at 1015h, 1315h, and 1615h.
Cannabis Administration


Cannabis (active: 4.91% CBD/2.98% THC and inactive: 0% CBD/THC) will be provided by the National
Institute on Drug Abuse (NIDA). At three timepoints each day, participants will smoke 75% of one
cannabis cigarette (800 mg) at each time point (1000, 1300, 1600) using our standardized paced puffing
procedure [6]. Using an intercom, an investigator will signal ‘light the cigarette’ (30 sec), ‘prepare’ (5
sec), ‘inhale’ (5 sec), ‘hold smoke in lungs’ (10 sec) and ‘exhale’ with a 40-sec interval between each
puff; cannabis administration will be blind to the participant.
 
Explain the reason(s) subjects may be withdrawn or terminated from the study.
If you do not anticipate withdrawing or terminating subjects from the study, please state that in this box.
Withdrawal Criteria and Procedures.
--Subjects will be informed that they have the right to withdraw from the study at
any time for any reason, without prejudice to their medical care. The Investigator also has the right to
withdraw subjects from the study for any of the following reasons: non-adherence to protocol
requirements; unwillingness to continue in the study; medical judgment of the Investigator.
Withdrawal of Subjects from Study.
--Subjects must be withdrawn from study therapy and withdrawn from the study if
any of the following occur: In the Investigator’s medical judgment, further participation would be
injurious to the
subject’s health or well-being (as determined by the study physician); Positive serum or urine pregnancy
test, confirmed by a serum pregnancy (serum human chorionic gonadotropin) test result; AEs occurring
that in the opinion of the Investigator may constitute a potential risk for continued participation by the
subject (e.g., extreme paranoia resulting from cannabis administration); Major protocol violation as
discussed and agreed upon between the Sponsor and Investigator; Consent is withdrawn; Termination of
the study by the Sponsor; Termination of the study by the local
health or regulatory authority or Institutional Review Board (IRB).
COVID-19 Early Discontinuation Procedures.
--Participants will be removed from the study if they display any symptoms
of an upper respiratory infection (cough, fever, coryza). The appropriate referral will be made (e.g.
emergency
department, home with outpatient follow up via telemedicine) depending on the participants clinical
status. COVID-19
testing may be performed prior to discharge; if so results conveyed to the participant when results return
in 3-4 days. If sent home, participants will be instructed to self-quarantine until the COVID-19 tests
results are available, and further recommendations made upon test results
Participant Study Termination Resulting from Adverse Events from Pain Testing.
--The Cold Pressor Test (CPT) may induce a rise in blood pressure and/or heart rate. If this occurs (to
standards described below), the CPT will immediately be stopped, and the participant will be withdrawn
from the study if heart rate or blood pressure values exceed safe limits. Emergency medical equipment is
available in our laboratory, which is in a hospital where a full medical emergency back- up team is
constantly available. Participants will perform the cold pressor test during training, and if their heart rate
exceeds 160, their systolic blood pressure exceeds 180, or their diastolic blood pressure exceeds 110,
they will be discharged from the study by the Investigator. Vital signs will be taken before, during, and
after the CPT assessment during training. During laboratory sessions, if systolic blood pressure of greater
than 180 or a diastolic blood pressure greater than 110 (each measure confirmed by manual reading), in
which either is sustained for more than 120 sec. is observed, the CPT for that participant will be
suspended for that given day. In addition, a single reading of systolic blood pressure greater than 200, or
a single reading of diastolic pressure greater than 120 (each measure confirmed by manual reading), or a
confirmed heart rate of greater than 160, will result in suspending the CPT for that participant for that
given day. If any of these parameters is exceeded, we will immediately confer with a staff internist to
determine whether the episode of hypertension or tachycardia is resolving and can be followed up on an
outpatient basis, or whether acute medical intervention is indicated. We will also continue to take that
participant’s vital signs every 30 minutes until the episode has resolved or until a staff internist
determines that acute medical intervention is indicated. If these changes are observed on a second
occasion, the CPT will not be administered again to that participant.
Drug Supplement (1 of 1)


Please fill out this Drug Supplement for EACH drug. Once completed click "Repeat" at the
bottom of the page to enter another drug. Once all drugs have been entered click "Next"
Please enter the name of the study drug.
Cannabis
Is the drug approved by the FDA?
No
Is the drug being used in accordance with labeling?
No
Does use of the drug meet the requirements for exemption from IND requirements?
No
Has an IND been issued by the FDA?
For more information on Sponsor-Investigator responsibilities, please refer to: FDA Information 
Yes
Provide the IND number.
36369
Name the person/entity that holds/is the Sponsor of the IND.
If the IND holder is an OMH investigator, please contact the IRB for information on responsibilities of
Sponsor-Investigators.
Meg Haney, Ph.D.
Please attach any correspondence from the FDA with your submission.
IND Ownership Transfer to Dr. Haney 2023
FDA Correspondence
RWF IND 036369 updates_8016_9.26.22.pdf
FDA Correspondence
rwf IND Form of Notice_8016.pdf
FDA Correspondence
RWF IND_1571+PSF_add 8016_6.8.22.pdf
FDA Correspondence
Subjects
Target Enrollment:
This refers to the target subjects enrollment, i.e., the number of subjects necessary to complete research
objectives.
20
Total number of subjects requested to reach target enrollment:
This refers to the estimated number of subjects you must "over-enroll" to meet your target enrollment
either by active screening or review of records for eligibility.
24


Please identify the groups of the study and how many subjects will be enrolled in each group.
 
Click "save" at the end of each row.
If you have multiple groups, please use the number (#) assigned to each group on the left of this table
to indicate that group in the inclusion/exclusion criteria table (to specify which inclusion/exclusion criteria
belong to which subject group).
Numbers here should equate to the number entered for Target Enrollment.
#
Subject Group
Subject Number
1
Healthy, non-treatment seeking heavy cannabis smokers
20
Please provide a justification for your sample size.
Power calculations were performed using G*Power, with the following assumptions: significance level of α
= 0.05, effect size (Cohen’s d) of 0.7, and within-subjects correlations of 0.6 for repeated measures.
Based on our residential laboratory studies in cannabis smokers, we estimate that 4 of the 24
participants may drop out. The large within-subject correlations (typically ranging from 0.60-0.95)
between conditions (active cannabis vs. inactive cannabis) allow for sufficient statistical power with n=20
completers.


Inclusion & Exclusion:
Give detailed inclusion and exclusion criteria (per group, if you have multiple groups). Note that order
does not indicate importance. Click Save at the end of each row to both save data and to add a new row.
For the final row, click Save and leave the new row blank.
Remember, if you have multiple groups, the column labeled as "Subject Group #" should match the
number (#) in the column "#" from the Subject Group table (section above).
Inclusion Criteria
Subject
Group #
Inclusion Critereon
Method for Ascertainment
1
Males or females, 21-60
years old
Medical exam, patient-provided identification
1
For women: not pregnant
or breastfeeding,
and using an acceptable
form of birth
control (e.g., condoms,
IUD)
Self-report during clinical interview and medical exam, urine
pregnancy test conducted under screening procedures and on
move-in day
1
Reports smoking cannabis
≥ 5 days per
week, equivalent to ≥ 2
joints (~0.4
grams/joint) per day for
> 4 weeks prior to
screening
Self-report during clinical interview and medical
exam, urine toxicology
1
Not seeking treatment for
cannabis use
Self-report during clinical interview and medical
exam
1
Able to provide informed
consent
Self-report during clinical interview and medical
exam
1
Able to perform study
procedures
Self-report during clinical interview and medical
exam, training sessions
1
Participation in Screening
Study #7091R
Enrollment and completion of screening study #7091R
Exclusion Criteria
Subject
Group #
Exclusion Criterion:
Method for Ascertainment
1
Meets DSM-V criteria for any Substance
Use Disorder other than cannabis, nicotine or
caffeine
Self-report during clinical
interview and medical
exam
1
Uses other illicit drugs ≥1 day/week in the
prior 4 weeks
Self-report during clinical
interview and medical
exam, urine toxicology
1
If medical history, physical and psychiatric
examination, or laboratory tests performed
during the screening process revealed any
significant illness that the study physician deems
contraindicated for study participation
(e.g., hypertension, defined as BP >140/90
and/or resting heart rate (HR) > 90)
Self-report and current
medication use during
clinical interview and medical
exam, bloodwork
1
Current illicit use of medical cannabis, Rx
analgesics, daily OTC or supplement use, or
Self-report during clinical
interview and medical


Subject
Group #
Exclusion Criterion:
Method for Ascertainment
any medications that may affect study
outcomes
exam
1
Current pain
Self-report during clinical
interview and medical
exam
1
Insensitivity to the thermal stimuli of the
Cold Pressor Test or Quantitative Sensory
Testing
Training session
1
Nicotine users, defined as smoking > 10
tobacco cigarettes/Day in prior 4 weeks, as
nicotine use and withdrawal has
demonstrated significant effects on pain
perception
Self-report during clinical
interview
Demographics:
Demographics collected
Please complete the below fields to report your anticipated recruitment demographics.
If you are targeting a specific gender, age, race, or ethnicity, please indicate in the Inclusion Criteria.
   Population Gender
Population
Age
Population
Ethnicity
Population Race
☑Male
☑Female
☐Transgender/non-binary/non-
conforming
☑18-65
☐>65
☐0-7
☐8-17
☑Hispanic or
Latino
☑Not Hispanic or
Latino
☑American Indian or Alaska
Native
☑Asian
☑Black or African American
☑White
☑Native Hawaiian/other
Pacific Islander
Indicate all vulnerable populations that will be enrolled in this research (select all that apply).
Only indicate subjects who will be targeted for enrollment.
Pregnant women=Women who are pregnant upon enrollment. Although not targeted, if your protocol will
follow women who become incidentally pregnant during the course of the study, please check this box.
NONE=No Vulnerable Populations will be enrolled in this research.
☐Children
☐Prisoners
☐Pregnant Women
☐Fetuses/Neonates
☐Individuals with impaired decision making
☐Illiterate subjects
☐Non-English speaking subjects
☑None of the above regulatory considered categories.


Indicate all other research populations of interest that will be enrolled in this research (select
all that apply).
 
☐Inpatient
☐Adults over the age of 60
☐A mental hygiene 33.13 archival
☐Research on students
☑None of the above considered categories
Recruitment
Describe the recruitment process, including how subjects will be identified and selected for the
study. Describe in detail how participants will be recruited including methods such as
advertisements, private practices, clinics, phone screening, review of records, use of websites,
etc. Be sure to include the following information in your description:
When, where, by whom and how potential participants will be approached.
If posting on your Facebook page or other social media sites, please explain.
If you will recruit by e-mail, phone, etc., explain how the researcher will obtain the
participants’ contact information.
Please be reminded that researchers cannot directly approach a patient for recruitment until that patient
has been informed of the study by their physician or a member of their treatment team who has
ascertained that the patient is willing to discuss the study with the investigators.
Recruitment is the first step of the informed consent process and should be considered in terms of the
first interaction with the subjects or their data.
Is direct contact with subjects being used for this study?
Yes
Are you using a pre-screening process for subject selection?
Pre-screening is used for selecting and finding research participants prior to consent.
Yes
Please describe the pre-screening process.
Potential participants will complete a telephone interview to assess initial eligibility (conducted under
screening protocol (7091R) before being invited for in person screening. After reading, discussing, and
signing informed consent, volunteers will complete two screening visits. The first will be conducted under
screening protocol 7091R, which includes a physical examination by the study physician, as well as lab
work (routine bloodwork and urine toxicology). The second will be conducted under 8016, after initial
eligibility is confirmed under 7091R. Two separate consent forms and HIPAA forms will be signed (one for
7091R, and one for 8016).
Describe the recruitment process
Eligible participants will be recruited from the New York, NY area. Recruitment for this study will occur
primarily through advertisements in local newspapers, online through Craigslist and Columbia's
RecruitMe, and by word of mouth. Potential participants will be screened for initial eligibility for cannabis
lab studies under our IRB-approved screening protocol (7091R). If they meet general eligibility criteria,
they will be screened for study-specific criteria under 8016. Therefore all 8016 participants will be
selected from 7091R participants.


 At any point in the study, will you (select all that apply):
For more information on PII/PHI visit NKI PHI & PII Policy
☐Request doctor referrals for selection of potential subjects
☐Request information (i.e. subject Personally Identifiable Information (PII) and/or Private Health
Information (PHI)) from a record information system
☑Access information (i.e. subject Personally Identifiable Information (PII) and/or Private Health
Information (PHI)) from a record information system
☑Use advertisement materials (i.e. flyers, phone calls, emails, etc.)
☐None
Indicate how you will obtain data from the record system (select all that apply):
☑Obtaining record system hard copy records specific to research subjects
☑Obtaining data from a record system digitally
If you are obtaining data from a health record information system(s), you will need to indicate
whether you plan to receive a data extract or whether you plan to access the information
system(s) directly to create a data set.
Extract is when the facility responsible for housing/safeguarding the record system provides the data set
directly to the researcher. When receiving a data set through data extract, the researcher may indicate
whether the data elements should be provided with identifiers, or as a de-identified dataset with no way
of linking any identifying information.
Access to an information system means that the researcher may directly access a health record
information system and create a data set for the research study.
Please list each system from where data will be obtained. Then indicate if you plan to Access or
Extract the data from the system.
In order to add additional systems click "save" at the end of the entry.
Information System
Obtaining Data
KisEMR
☑Access
☐Extract
SURC server
☑Access
☐Extract
Do you intend to receive only de-identified data from the record system(s) in your research
study?
No


Indicate which recruitment methods will be utilized. Select all that apply:
☑Flyers
☑Newspaper Advertisement
☐Radio/Television Advertisement
☑Online Advertisement--Including Social Media
☐Letters or Emails
☐Phone Call
☐Group or Class Presentation
☐Other
It was indicated that flyers will be used as recruitment in this study. Please attach flyer(s)
below.
It was indicated that Newspaper Advertisements will be used as recruitment in this study.
Please attach Newspaper Ad(s) below.
It was indicated that Online/Social Media Advertisements will be used as recruitment in this
study. Please attach text, page mockup, or description of posting including any images below.
Please attach all recruitment materials 
Must be a Word Doc
8016 advertisement
Advertisement
Consent & HIPAA


Select all applicable methods of consent below to indicate the informed consent process that
will be used.
 Signed Consent
 
  
 Waiver of signed Consent
Check here indicating that a waiver of consent documentation is being requested in accordance with
Federal Regulations 45 CFR 46.117 / 21 CFR 56.109.
Common procedures where this applies includes, but are not limited to:
Use of telephone consent or phone screening (provide a copy of the screening script if this
choice is made)
Use of internet surveying (provide the method that the survey will be distributed and language
that will be provided to the subjects)
A signed consent would jeopardize the subject (provide the consent document that will be
handed to the subject. This document should not contain signature lines)
   
 
 Alteration to Consent
Check here indicating that an alteration to the elements of consent is being requested in accordance
with Federal Regulations 45 CFR 46.116 / 21 CFR 56.109
Common reasons to indicate this choice include
Use of deception in research. Explain in study procedures why deception is warranted and detail
the elements of consent that will be excluded. Please also provide your plan for debriefing (who will
conduct debriefing and when). Please sure to include your debriefing form.
  
  
 Full Waiver of Consent
Check here indicating that a waiver of consent is being requested in accordance with Federal
Regulations 45 CFR 46.116 / 21 CFR 56.109.
Common reasons to indicate this choice include
Chart reviews, archival data (i.e. MHL 33.13), etc.
Per earlier selections, Illiterate and/or Non-English speaking individuals are being excluded.
New York State requires the inclusion of these groups in studies obtaining written or verbal
consent, unless justification is provided. Please provide a justification for the exclusion of
Illiterate and/or Non-English speaking individuals.
Illiterate and/or Non-English speaking individuals are excluded from this study because they would not be
able to accurately respond to the written data collection instruments, which would negatively impact data
integrity.


A protocol which does not include an informed consent process may be approved by the IRB
under certain conditions. To request IRB approval of a protocol which does not include an
informed consent process, please provide a response to all of the following questions. Please be
specific in explaining why each statement is true for this research. Completion of this box
implies the research (or portion of the research for which the waiver was requested) involves
no more than minimal risk to the subjects.
*Use of identifiable information/biospecimens to identify potential subjects (i.e., screening for
recruitment purposes) is allowed without informed consent under certain circumstances. A waiver of
consent will no longer be needed for these screening activities.
Explain why and how the research involves no more than minimal risk to the subjects.
While the overall study does involve more than minimal risk (drug administration), we are asking for a
waiver of signed consent for screening purposes which do not present more than minimal risk.
Participants give electronic and verbal consent during the 7091R screening process, during which PHI is
obtained. When they come to NYSPI to complete additional screening, they sign a hard copy of the
consent form.
Explain why the waiver will not adversely affect the rights and welfare of the subjects.
Participants sign a hard copy of the consent form when they come to NYSPI to complete additional
screening procedures.
Is the research team collecting identifiable private information and/or identifiable
biospecimens?
Yes
If yes, explain why the research could not practicably be carried out without using such
information or biospecimens in an identifiable format.
They complete preliminary screening, which includes collection of PHI (name, age) over the phone.
Explain why the research could not be practicably be carried out without the waiver of
informed consent.
They complete preliminary screening over the phone following verbal consent, which includes collection of
PHI (name, age).
If a waiver of informed consent is approved by the IRB, will subjects be provided with
additional pertinent information after participation?
No
Explain/describe why or why not
Participants receive all necessary information verbally over the phone. When they come to NYSPI, they
sign a hard copy of the consent.
Will any of the study procedures include collecting photographs, audio recordings, and/or video
recordings?
For guidance see our policies on your dashboard in the Notices section
This would include collection of MRI images.
N/A – No photos, audio or video recordings will be taken


Identifiable Information
Does this study use or collect any of the below?
☑Names
☑Medical record numbers
☑Phone numbers
☐Fax numbers
☑Electronic mail addresses
☑Social Security numbers
☐Account numbers
☐Certificate/license numbers
☐Device identifiers and serial numbers
☐Web Universal Resource Locators (URLs)
☐Internet Protocol (IP) address numbers
☑All elements of dates (except year)
☐Health plan beneficiary numbers
☐Vehicle identifiers and serial numbers, including license plate numbers
☐Full face photographic images and any comparable images
☐Biometric identifiers, including finger and voice prints
☑All geographical subdivisions smaller than a State, including street address, city, county, precinct, zip
code, except for the initial three digits of a zip code
☐Any other unique identifying number, characteristic, or code (note this does not mean the unique code
assigned by the investigator to code the data)
☐None of the above will be collected
Will you collect health information as part of research procedures associated with this
protocol?
Yes
Please be advised you are using Protected Health Information and need to have a process for
Authorization. Both options below may be required for some protocols.
☑Subjects will sign a HIPAA Authorization form
☑Requesting a Waiver of HIPAA Authorization (45 CFR 160 and 45 CFR 164)
Based on previous answers, you must select "Requesting a Waiver of HIPAA Authorization".


Waiver of HIPAA
Please answer all four questions to submit your request for a Waiver of HIPAA Authorization.
1. Explain how the research presents no more than minimal risk to the subjects’ privacy.
While the overall study does involve more than minimal risk (drug administration), we are asking for a
waiver of HIPAA for screening purposes which do not present more than minimal risk. Participants give
electronic and verbal consent during the 7091R screening process, during which PHI is obtained. When
they come to NYSPI to complete additional screening, they sign and receive a hard copy of the HIPAA
Authorization form.
2. Explain why the research could not be conducted without the Private Identifiable
Information.
We need to gather information over the phone related to their identity (name) and age to confirm
preliminary eligibility. Participants sign a hard copy of HIPAA when they come to NYSPI to complete
additional screening procedures.
3. Describe your plan to destroy the identifiers as soon as possible consistent with the conduct
of the research or provide a health or research justification for retaining the identifiers or
explain how retention is required by law.
All data records containing identifying information will be kept in locked files and on password-protected
computers. Only the principal investigator and other core study staff will have access to identifiable
information, which will be maintained on site under lock and key. All computer data is stored without
names or other identifiers. Participants will be identified only through a numerical code in all electronic
databases. PHI data will be kept for 6 years (per HIPAA guidelines) and then destroyed.
4. Will the identifiable information be reused or disclosed to any other person or entity outside
NKI/RFMH other than those identified in the protocol, except as required by law, for
authorized oversight of this research study, or as specifically approved for use in another study
by an IRB?
No
Attach Consents
Attach Consents, Consent Waiver Scripts, Parental Permissions, or Assents Forms 
8016.CF_4.14.23.pdf
Consent
Consent Quiz
Consent
 
Must be a Word Doc
NKI How to Use Consent Language and Template(s)
NKI Sample Consent Language
NKI Standard Consent Template
NKI Clinical Trial Consent Template
NKI Assent Template
NKI Consent Form Addendum Template
NKI Phone Screening Guidance
NKI Information Sheet for Waiver of Documentation of Consent
Attach HIPAA
Must be a Word Doc
OMH/OPWDD HIPAA Authorization Template
OMH/OPWDD HIPAA Parental Permission Authorization Template
PP1 Notice of Privacy Practice
HIPAA
HIPAA Authorization
Future use, Privacy, and Confidentiality


Are there plans to use the data and/or specimens collected for this current study in future
research?
No


Confidentiality
Describe the plan for protecting the confidentiality of the data/specimens collected as part of
this research.
There are many ways to protect subject confidentiality. Common method includes the assignment of a
code number to the data/specimen, separated from the subjects’ name or other identifying information.
Methods to protect confidentiality. Potential participants divulge information that is sensitive and may
have adverse social consequences if released. This would include information released to insurance
companies, health care agencies, family members, or made public in any way. This study is NIH-funded
and thus automatically covered by a Certificate of Confidentiality, and procedures for protecting
confidentiality of records will be followed. Specifically, all data records containing identifying information
will be kept in locked files and on password-protected computers. Only the principal
investigator and other core study staff will have access to identifiable information, which will be
maintained on site under lock and key. All computer data is stored without names or other identifiers.
Participants will be identified only through a numerical code in all electronic databases.
Following the NYSPI Remote Communications Guidance, confidentiality of remote communication is
protected using secure, HIPAA-compliant telecommunication (e.g., Webex, Zoom, Facetime, telephone, or
Google Voice) in combination with digital data collection procedures (through remote access to secure
NYSPI systems). Additionally, all email communications will be encrypted.
Provide a description of the protections in place to safeguard participants' privacy while
information is being collected, such as where will you conduct the consent process or collect
data from interaction with the subject.
Minimizing risks associated with the study procedures--
Prospective participants will be recruited into the study through advertisements in local newspapers and
an online classifieds site (CraigsList). All advertisements will be approved by our IRB prior to posting.
Prospective participants will first receive a general consent form covering the screening and evaluation
processes. Next, they will be evaluated by a study team consisting of research psychologists, nurses, and
physicians. These screening assessments include: a standard psychiatric evaluation that includes an
abridged Structured Clinical Interview for DSM-V Disorders (SCID-V), mental status examination, physical
examination, and laboratory assessment. The study principal investigator and research physician will
review each participant’s history, mental status exam, and medical evaluation and determine whether the
participant is eligible and competent to consent. Individuals who meet inclusion/exclusion criteria will be
offered participation in the proposed investigation. The study PI and
research physician will describe the study in detail, including study procedures, and possible risks and
benefits of
participation. Participants may sign the consent form only after reading it, having any questions
answered, and being
given a copy to keep. Participants will be scheduled for laboratory sessions after they complete this
screening and
informed consent process. We will also strictly implement our inclusion/exclusion criteria. Participants are
excluded if they have severe psychiatric illness (e.g. mood disorder with functional impairment or suicide
risk, schizophrenia) that might interfere with their ability to participate in the study or their capacity to
provide informed consent; current use of amphetamines, cocaine, antihistamines, tricyclic
antidepressants, barbiturates, benzodiazepines, opioids, other Rx or over-the-counter analgesics, or
muscle relaxants are exclusionary because of the risk of concomitant side effects and study confounds
(participants will be instructed not to use any of these drugs during the study period); meeting DSM-V
criteria for a Substance Use Disorder for any drugs other than caffeine, nicotine, or cannabis; pregnancy
is exclusionary due to the possible effects of cannabis on fetal development; the evaluating psychiatrist
reviews all medical assessments along with medical history; history of an allergic reaction to cannabis.
These criteria are designed not only to optimize study findings but also to minimize risk to participants. In
addition to strict implementation of our inclusion/exclusion criteria, we will also take vital signs regularly
throughout the duration of the study in order to maintain the safety and well-being of participants,
specifically during the repeated pain challenges. During the inpatient stay, participants will have vital signs
taken each morning (Table 2). Vital signs will also be taken before and after each pain assessment, as
well as one additional time halfway through the duration of each CPT. On pain testing days we will also
measure vital signs before the second cannabis administration of the day, as well as in the late afternoon
once participants have completed that day’s tasks (Table 2). If any participant experiences sustained
increased blood pressure response to the CPT (systolic > 180 or diastolic > 110 for over 120 seconds) we
will stop the CPT immediately in order to protect the participant. We will confer with a staff internist and
continue to monitor the participant’s vital signs every 30 minutes until the episode has resolved or until
the staff internist has determined that acute medical intervention is indicated. In addition to closely
monitoring vital signs during pain assessments, we will also ensure that there is significant recovery time
between sets of repeated pain challenges. Staff members will be present with participants for the entirety
of the pain assessments, including time in between assessments. This allows for constant monitoring of
the participant’s safety. Minimizing COVID-19 exposure risk. To reduce the risk of participants being
exposed to COVID-19 during study participation, participants will be informed of all NYSPI’s safety
guidelines prior to study enrollment. If enrolled, participants will be strictly required to follow these safety
guidelines while on-site. Additionally, research staff will strictly follow all safety guidelines while
interacting with study participants.


Minimizing COVID-19 exposure risk--
To reduce the risk of participants being exposed to COVID-19 during study participation, participants will
be informed of all NYSPI’s safety guidelines prior to study enrollment. If enrolled, participants will be
strictly required to follow these safety guidelines while on-site. Additionally, research staff will strictly
follow all safety guidelines while interacting with study participants.
Will data/specimens be shared with anyone outside of NKI/RFMH?
No
Risk, Benefit, Compensation, & Alternatives


Risks
Identify all research-related risks of harm to which the subject will be exposed for each
research procedure or intervention as a result of participation in this study.
Consider the risks of breach of confidentiality, psychological, legal, social, and economic risks as well as
physical risks. Do not describe risks from standard care procedures; only describe risks from procedures
done for research purposes. Include data on risks that have been encountered in past studies. Related
to past studies, list all risks that occurred.
For Clinical Trials, Adverse Events from animal or human studies should be detailed or referenced in this
section.
Cannabis administration
Participants will be administered one of two smoked cannabis conditions (active: 4.91%THC:2.98% CBD
or placebo: <0.01%THC:CBD) during the active phase of the laboratory study. The most frequently
reported adverse experiences associated with cannabis administration include changes in the pattern of
heart beats, heart pounding, paranoia, slurred speech, loss of coordination, dizziness, shakiness,
clumsiness, lightheadedness, confusion, faintness, concentration difficulties, dependence, restlessness,
sleepiness, fatigue, itching, sweating, flushing, paleness, headache, dry mouth, stomach upset, and
increased appetite.
Cannabis abstinence/withdrawal
During the inactive phase of the laboratory study, participants will be administered inactive smoked
cannabis (<0.01% THC:CBD); this abrupt cessation of cannabis use can induce cannabis withdrawal. The
most frequently reported adverse experiences associated with cannabis withdrawal are anxiety, mood
changes, aggression, anger, irritability, nervousness, shakiness/tremors, restlessness, difficulty sleeping,
decreased appetite, weight loss, abdominal pain, sweating, fever, chills, and headache.
Describe all measures implemented to minimize risks of harm (precautions, safeguards).
Risks of cannabis administration, abstinence, and withdrawal:
This study administers cannabis and has daily cannabis users undergo abrupt cessation of use. The effects
of cannabis administration and the possible onset of cannabis withdrawal symptoms is described to
participants before study onset. As part of our informed consent procedures, we describe the effects of
cannabis administration (e.g., dry mouth, increased heart rate) and the potential consequences of abrupt
cannabis abstinence (e.g., irritability, difficulty sleeping, decreased appetite). We also list these symptoms
in the consent form. All side effects will be reported to the study investigator to discuss severity. Expected
effects of cannabis administration or abstinence will be recorded but not reported as AEs unless deemed
severe (Grade 3 or above). Any symptomology that is considered clinically significant or that was not
described in the consent form will be documented in the adverse event log in the study regulatory binder.
Adverse event reporting will follow the guidelines set forth by the IRB of record and NYSPI and will be
recorded in the AE log.
The Cold Pressor Test (CPT):
The CPT requires the use of warm (36.5-37.5ºC/97.7-99.5ºF) and cold water (3.5-4.5ºC/38.3- 40.1ºF).
While the temperature of the warm water is characteristic of bath water, the cold water causes redness
and slight discomfort due to the nature of the assessment. Pain resulting from this assessment is acute,
resolves within minutes, and leaves no lasting effects. The CPT is also associated with cardiovascular
changes that include elevations on heart rate and blood pressure. Participant’s heart rate and blood
pressure will be taken before each CPT begins, halfway through each CPT session, and once each
assessment is complete. The CPT will be performed eight times during seven of the inpatient study days,
as well as once during the training session.
Quantitative Sensory Testing – Thermal Temporal Summation (QST-TTS):
QST-TTS requires the use of a thermode that begins heat stimulation at 32.0°C/89.6°F, increases at a rate
of 1°C/s, and reaches a temperature of 46.5°C/115.7°C, remaining constant for 120 seconds. The total
duration of stimulation is 135 seconds. While the nature of the task is to produce slight pain, the heating
element is designed not to exceed safe temperatures that could result in skin damage and has an
automatic shut-off feature. Patients will be evaluated during screening for any indication of nerve damage
using von Frey filaments. Potential risks during QST-TTS are minimal, which include a burn akin to a
sunburn. These happen extremely infrequently (<1%) and are not expected to occur at the temperatures
utilized in this proposal. Vital signs will be taken before and after each assay. The QST-TTS will be
performed eight times during seven of the inpatient study days, as well as once during the training
session. Repeated QST-TTS is currently being conducted in two other studies within our group (#8016 and
#8058), and no issues have occurred to date. Further, an investigator (Dr. Peggy Compton, University of
Pennsylvania) with experience in repeated QST-TTS is a consultant on this project and has provided input


that given sufficient time (10 minutes) between repetitions of testing, participants will be protected
against adverse reactions. Dr. Compton did not report any known contraindications of QST-TTS.
Repeated Pain Challenges:
Both the CPT and the QST-TTS will be performed eight times per day during seven of the inpatient days
and once during the training session. Repeated pain challenges may temporarily increase blood pressure
and heart rate and cause some discomfort in the case of the CPT. The QST-TTS has not been found to
have any cardiovascular risks. Participants will be given sufficient time to recover between sets of
repeated pain challenges.
Inpatient Research Designs:
The problems associated with living in the inpatient laboratory have been minimal in the participants we
have tested in similar types of protocols. We describe at length the isolation, boredom, and inactivity
before volunteers sign the consent form, and thus far, have not encountered problems in this area. Of
course, participants are free to leave the study at any time, and care is taken to be sure that this option is
understood.
Pregnancy:
Female participants must be non-pregnant to be included in the study. A plasma pregnancy test will be
performed during screening and a urine pregnancy test will be conducted immediately prior to conducting
each training
visit and laboratory visit.
COVID-19 Exposure:
Participants will be required to travel to NYSPI for outpatient sessions and will reside in the Cannabis
Research Laboratory’s Residential Laboratory in cohorts of two-four as part of their participation in this
study. Participants will be informed of the potential risk of contracting COVID-19 from infected individuals
while traveling to our laboratory in the study consent form and subsequent consent discussions with
research staff
COVID-19 Test:
A nurse or physician will put a cotton swab up both sides of the nose and move it around for about 15
seconds. Participants are informed of possible discomfort associated with collecting a nasal sample.
Benefits
Provide the current benefit to subjects involved in this study and the potential benefit that this
study offers for future research.
This description should be based on accrued data from related studies that have been completed. There
should be a rational description of why such benefits are expected based on current knowledge. If there
is no direct benefit to subjects of this project, make an explicit statement that there is no direct benefit.
This study will not provide any direct benefits to participants.


Subject Compensation
Will there be any compensation provided to subjects?
Yes
Please describe any compensation provided to subjects and justification for such
compensation.
Compensation is provided for participants' time and effort in the study. Participants are paid a $40 bonus
for each inpatient day if they complete the entire study. They are paid for each component prior to move
in at that visit, and then will be paid half of their total remaining compensation at move-out and asked to
come back one week later to receive the second half of their remaining total. Participants who arrive on
move-in day ready and eligible to participate but who were not selected (due to over- enrollment) will
receive $75 and be sent home.
1. Phone screen/Qualtrics, $ 20.00 (2 visits)= $40.00
2. in-person screening, $ 26.00
3. Training Visit, $50.00
4. Move in, $40.00
5. Inpatient Day (base), $50.00 (14 inpatient days)= $700.00
6. Inpatient Day (bonus), (14 inpatient days) = $700.00
7. Move out $20.00
Are subjects reimbursed for travel or other expenses?
Yes
Please describe any reimbursement for travel or any other expenses.
If you will compensate subjects $600 or more annually, you must include language in the consent form.
In addition to study compensation, participants will be given $6 for subway/bus fare for visits that require
travel to NYSPI (factored into the payment for in-person screening, move-in, move-out).
Total compensation:$1,576.00
Alternatives to Participation
Describe the Alternatives to Study Participation
An important alternative is also not to participate in this research.
This is not a treatment study for cannabis use or for pain; data are being collected for research purposes.
If participants are interested in treatment for their cannabis use, we will give them a referral to a
treatment program.
Participation is Voluntary:
Participation in this project is voluntary. If potential participants decide not to participate or if they later
decide to stop participating, they will not lose any benefits to which they are otherwise entitled. A decision
to not participate or withdraw participation will not affect current or future treatment at the New York
State Psychiatric Institute or Columbia University. Participants will be informed of any new findings or
risks that arise that may affect their willingness to continue in this study. The investigator may also decide
that their participation should be discontinued under certain circumstances (e.g., following an adverse
event).
Data Management, Data Monitoring, Reportable Events, and Incidental Findings


Data Management
Include in this section the plan for acquiring data (both electronic and hard copy).
For example, if you are obtaining data from a record system, what is your plan for obtaining access to
the system (if applicable) or receiving the data from an administrator of that system (if applicable). Be
sure to include plans for all data, including paper and pencil survey. 
 
 
We will be using secure web-based central electronic data capture systems (e.g., Acquire EDC, REDCap,
etc.) for automated data collection. This electronic data capture systems ensure the privacy and security
of the data collected by meeting the Good Clinical Practice (GCP) guidelines and the following applicable
Federal Regulations-Health Information Portability and Accountability Act (HIPAA), Federal Information
Security Management Act (FISMA), and Food and Drug Administration (FDA) 21CFR Part 11. Access to this
database is limited to research approved personnel, who have received training on handling human
subjects’ data and systems training. The principal investigator or a qualified data management staff
member will train research assistants on how to properly enter data into and review and resolve data
queries in the electronic data capture systems. Study data such as subjective-effects, self administration,
and other objective and subjective ratings will be entered into Research Electronic Data Capture
(REDCap)—a secure, HIPAA-compliant, FDA 21 CFR Part 11 compliant, web-based application.
All virtual participant assessments and videoconferencing sessions will be hosted via Zoom or WebEx—
secure, HIPAA-compliant video conferencing recommended by NYSPI (using institutional accounts only).
For participants with email access, any study related information that contains PHI will be sent via
encrypted email. The Principal Investigator will identify a single qualified research member who will have
access to and manage the REDCap database, under the PIs supervision. If significant changes are made
to the data management plan we will submit those as protocol amendments.
Study team members that have regular access to records and data include research assistants, the study
coordinator, sub-investigators, the principal investigator, and study physicians when necessary. As
previously mentioned, all physical subject records including screening folders and case report forms are
securely stored in locked cabinets within room 3602 on site, and any electronic data is password
protected on the SURC server that can only be accessed by the study staff.
Data Storage
Describe the storage location (for both electronic or hard copy files), length of time stored, and plan for
destruction.
If storing data on devices (including laptops, workstations, flash drives, backup tapes, etc.), please
attest that the devices are encrypted and protected with a strong password (Example: “Hardcopy
records will not be maintained for this study; Electronic records will be maintained on the password
protected file on the HIPAA drive”). Be sure to include who has access to these devices.
Data storage for this study involves both hard copy and electronic versions. Electronic-captured data, such
as Inquisit tasks, occur on ResLab laptop where participant responses are then transferred to a hard
drive. Once on the hard drive, all data is exported to our lab's server. Any forms of hard copy data are
transcribed by two different study personnel onto password protected files and maintained onto the lab's
server. All devices and hard drives are encrypted and protected with a strong password.
After the transfer onto the server, hard copy data is stored in locked storage cabinets within the lab (room
3602). Only study personnel (PIs, Research Assistants, and study staff) have access to the electronic and
hard copy files of data, due to restricted password or key access.


Specimen Storage and Management
Managing and Storing Specimens
Include in this section the plan for acquiring specimens.
For example, will specimens be collected by the research team, or will they be received in another way?
Please detail this process.
Blood samples are collected by the research team during screening as a part of routine lab work to
confirm participants are healthy prior to enrollment. During the screening process, the staff collect urine
as part of the screening protocol (7091R). The collected samples are promptly disposed of and are not
stored as LabCorp destroys samples in the second section.
Describe the storage location, length of time stored, and plan for destruction.
Blood samples are sent out to LabCorp and are not stored on site at NYSPI. Blood samples are destroyed
by LabCorp after bloodwork is run.
Data Monitoring
All studies should have a plan for monitoring study data. The need for a formal committee or a
designated study team monitor is based on the risk of the study design.
Is there a Data Monitoring Committee (DMC), Data Safety Monitoring Board (DSMB), or other
monitoring entity for this study?
Yes
Detail who comprises this committee:
Caroline Arout, PhD (PI)
Jeanne Manubay, MD (study physician)
Detail what will be monitored:
Both the principal investigator and study physician will provide ongoing review of the data and safety of
the study participants during daily communication with the research staff, as well as at weekly lab
meetings. In addition, ongoing and annual review of any serious adverse events (SAEs) are monitored by
the Institutional Review Board (IRB) of the New York State Psychiatric Institute, the National Institute on
Drug Abuse (NIDA), and the Food and Drug Administration (FDA). All AEs reported by participants or
observed by the research staff will be individually listed on our Adverse Event Form (AEF). The signs and
symptoms, time of onset, duration, severity, medical intervention, follow-up procedures, and suspected
relationship to study drug will be reported. Any AE (clinical signs and symptoms or laboratory test results)
associated with cannabis or oxycodone administration will be documented by the study physician and
nurse. If any SAEs occur during this study, they will be reported to the IRB, NIDA, and the FDA, which will
review the SAE report and suggest appropriate actions and, if necessary, study modifications. The
Principal Investigator and study physician will determine whether the seriousness of the event warrants
removal of any participant from the study.
A. Data Entry and Checking
1. Every data EXCEL sheet has a tab for a data progression log; any time anything is entered or edited, it
is noted in the progression log including the date, the initials of person handling the data and what section
of the data was entered.
2. There are two approaches for assuring data integrity:
-- a. Some data is entered independently by two individuals, e.g., double-entered. The data is entered
twice into identical tabs of a spreadsheet and then a formula is used to compare the tabs and search for
differences. e first and second entries are done by two different people. See below for instructions on how
to create compare formula.
--b. Some data is entered by one individual and a second person then double checks it for accuracy. See
below for the double-checking procedure
Detail the frequency of review:
Formal monitoring of participant records will occur monthly, where the PI will review all records of 10% of
study charts. Participant issues will also be discussed weekly with the research team at our lab meeting.


Reportable Events
Events that occur in research that may represent unanticipated problems involving risks to
subjects or others should be promptly reported using the Event report form within 10 days of
the investigator’s or research staff member’s learning of the event, except for these
circumstances:
1. If the event is related to a fatality that is related to study participation or possibly
related to study participation, the incident  should be report to the IRB within two (2)
business days of discovery of the event.
2. Events resulting in temporary or permanent interruption of study activities by the
investigator, sponsor, or DSMB (Data Safety and Monitoring Board) to avoid potential harm
to subjects should be reported within IRB within two (2) business days.
Incidental and Unexpected Findings
Incidental findings are observations of potential clinical significance unexpectedly discovered in research
participants and unrelated to the purpose or variables of the study.
Describe the plan to address incidental findings and unexpected findings about individuals
from screening to the end of the subject’s participation in the research.
In cases where the subject could possibly benefit medically or otherwise from the information, state
whether or not the results of screening, research participation, research tests, etc., will be shared with
subjects or their primary care provider.
In cases where the participant could possibly benefit medically or otherwise from study screening or other
information, the results of screening, research participation, research tests, etc., will be shared with
subjects and/or their primary care provider upon consent from the participant.
Data Analysis and References
Statistical/Data Analysis Plan
List the statistical methods to be used to address the primary and secondary objectives,
specific aims, and/or research hypotheses.
Explain how missing data and outliers will be handled in the analysis. The analysis plan should be
consistent with the study objectives. Include any sub-group analysis (e.g., gender or age group).
Specify statistical methods and variables for each analysis. Describe how confounding variables will be
controlled in the data analysis.
All data analyses will be based on models using repeated measures analysis of variance (RM-ANOVA)
analyzed as a function of cannabis condition (active vs. inactive) and day (Day 1-15), and sets of planned
comparisons, calculated with SPSS or SUPERANOVA statistical packages. The planned comparisons,
outlined below, are a priori, and designed to test the specific hypothesis for each aim. Tests of differences
for all comparisons will be based on F-statistics with degrees of freedom corrected, depending on the
observed within-subject correlation of the measures, using the method of Geiser and Greenhouse or
Huynh and Feldt. Results will be considered statistically significant at p < 0.05, using 2-tailed tests.
Distribution of demographic variables (ethnicity, age, sex) will be described in terms of means, standard
deviations, proportions, and 95% confidence intervals, where appropriate.


Please list all references.
 
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Funding
Are there any changes being made to the Funding or COI information?
Yes
Please indicate the origin of the project. (Who conceived of and leads the development of the
project, regardless of funding.). Select all that apply.
☑Investigator initiated (Investigator(s) developed protocol)
☐Industry (Pharmaceutical, Device, etc.) (Industry developed protocol)
☐Federal Agency (NIH, DOD, etc.)
☐Foundation Funding
☐Internal Funding
☐Other


Please state whether you receive Federal, State, Pharmaceutical Company, or other (be
specific) funding for the conduct of this project.
If you receive no funds, please list “No Funding” under “Funding Type.”
Funding
Type
Project Title
in Grant
Business
Office
Source
Source
Identifier....
(Grant #)
Subcontract
Subcontract
Institution
Funding
Start Date
Funding
Expiration
Date
No
funding
No Funding
NONE
No
Funding
No Funding
Subcontract
from:
No Funding
12/31/2023
Industry Effects of
Repeated
High-
Cannabidiol
Cannabis
Administration
on
Experimental
Pain and
Abuse Liability
in Humans
RFMH
Alkermes No grant
number
No
subcontract
01/01/2020 12/31/2023
If applicable, please indicate the which institution the grant or contract is funded through.
☐ Not Applicable
☑ RFMH
☐ NYU
☐ CU
☐ Other
Does any member of the study team have a Conflict of Interest?
Conflict of Interest is defined as a situation in which financial (funds paid outside of a sponsored project
agreement), non-financial or other personal considerations compromise, or have the appearance of
compromising, an individual’s professional judgment in proposing, conducting, supervising, or reporting
research (i.e., consulting, speaking, or acting as a Sponsor or Board member, etc).
If you are unsure about a COI please select "yes" and complete the following section.
No
Supporting Attachments


Please include any support attachments. NYSPI Investigators must upload their ancillary
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submitting an NHSR determination request, ancillary checklist and SRMP is not required.
Some items that may need to be attached include sample data collection sheets, Sponsor
Brochure/Protocol
Must be a Word Doc
8016 Continuing review form
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7091R (Evaluation protocol) consent form
Consent
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FDA Correspondence
IND ownership transfer correspondence 2023
FDA Correspondence
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8016 Ancillary Review Checklist and Attestation_CA.11.20.24 (1).pdf
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8016 Greenlight letter
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7091R (Evaluation protocol) PSF
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Upload all currently approved forms, even if they are no longer in use (i.e. you are in data
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8016_Ad_6.13.23_Final (1).pdf
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8016 updated HIPAA_3.7.23.pdf
HIPAA
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AE Log
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PD Log
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(PSF_2024) Effects of Repeated High_Cannabidiol Cannabis Administration on
Experimental Pain and.pdf
Protocol
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2025.4.8097.0/Release/5f5a7b9 | GCWAWS1 | 2025-04-14 18:59:42Z 

SAP_001.pdf: 
Title: Repeated Cannabis Administration on Experimental Pain and Abuse Liability 
NCT: 04576507 
Document date: April 14, 2025 
 
Statistical Analysis 
Overview: All data analyses will be based on models using repeated measures analysis of 
variance (RM-ANOVA) analyzed as a function of cannabis condition (active vs. inactive) and day 
(Day 1-15), and sets of planned comparisons, calculated with SPSS or SUPERANOVA statistical 
packages. The planned comparisons are a priori, and designed to test the specific hypothesis for 
each aim. Tests of differences for all comparisons will be based on F-statistics with degrees of 
freedom corrected, depending on the observed within-subject correlation of the measures, using 
the method of Geiser and Greenhouse or Huynh and Feldt. Results will be considered statistically 
significant at p < 0.05, using 2-tailed tests. Distribution of demographic variables (ethnicity, age, 
sex) will be described in terms of means, standard deviations, proportions, and 95% confidence 
intervals, where appropriate.