Clinical trial NCT02946489
Conditions: Cannabis Dependence
Keywords: cannabis mindfulness based relapse prevention motivational enhancement therapy
Sponsor: New York State Psychiatric Institute
Start date: 2016-10-01; Completion date: 2018-08-01
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Cannabis use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered cannabis use. Cannabis use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this single blind open-label trial is to test the feasibility of administering glutamate modulators in conjunction with motivational enhancement therapy (MET) and mindfulness based relapse prevention (MBRP) for cannabis use disorders.

Detailed description:
Individuals diagnosed with cannabis dependence will receive one or two infusions of glutamate modulators during week 2 and week 3 or 4. The participants will also receive 2-week course of MET and 4-week course of MBRP. Participants will meet with staff twice weekly, except for week 2 and potentially week 3 or 4 during which participants will present to the clinic three times. Clinic visits include MET sessions, MBRP sessions, psychiatric monitoring, assessments, and study procedures (e.g., medication administration).

Arms: arm 1: Administration of CI-581a during wk 2 and possibly at wk 3 or 4 at 0.71 mg/kg in the context of a 2 wk course of MET followed by a 4 wk course of MBRP
Interventions: intervention 1: CI-581a
Intervention descriptions: intervention 1: CI-581a will be administered in wk2 and potentially in wk 3 or 4.

Protocol documents:
Prot_000.pdf: 
Protocol Summary Form
7355
Dakwar, Elias
Page 1 of 19
Protocol Title:
Facilitating the Behavioral Treatment of 
Cannabis Use Disorders
Protocol Number:
7355
First Approval:
08/30/2016
Expiration Date:
08/21/2018
Version Date:
05/30/2018
Clinic:
BSU Clinical Service
Contact Principal Investigator:
Elias Dakwar, MD
Email: dakware@pi.cpmc.columbia.edu
Telephone: 646-774-8728
Co-Investigator(s):
Frances Levin, MD
Research Chief:
Frances Levin, MD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are no 
longer required, this option remains for historical purposes.
I am proposing an amendment only to an existing protocol
Division & Personnel
Division
What Division/Department does the PI belong to?
Substance Abuse
Within the division/department, what Center or group are you affiliated with, if any? 
Biological Studies Unit
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
No co-investigators


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Amendment
Describe the change(s) being made 
To add Craigslist to the recruitment options.
Provide the rationale for the change(s) 
We are seeking an alternative to print or radio ads.
Comment on the extent to which the proposed change(s) alter or affect risks/benefits to subjects 
It doesn
't.
Comment on if the proposed change(s) require a modification to the Consent Form (CF)
It doesn
't.
Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
   Medication Trial
   Use of Investigational Drug or Device
Population
Indicate which of the following populations will be included in this research
   Adults
   Adults over 50
Research Support/Funding
Will an existing internal account be used to support the project?
No
Is the project externally funded or is external funding planned?
Yes
Select the number of external sources of funding that will be applicable to this study
Funding Source #1
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
No
Who is the PI of the grant/contract?
Levin, Frances, MD
Select one of the following
The grant/contract is currently funded
Source of Funding


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Federal
Institute/Agency
NIDA
Grant Name
K24
Grant Number
DA029647
Select one of the following
Single Site
Business Office
CU
Does the grant/contract involve a subcontract? 
No
Study Location
Indicate if the research is/will be conducted at any of the following
   NYSPI
This protocol describes research conducted by the PI at other facilities/locations
No
Lay Summary of Proposed Research 
Lay Summary of Proposed Research
This project will evaluate the effect of one or two sub-anesthetic infusions of ketamine (0.11 mg/kg 2-min 
bolus followed by 0.6 mg/kg over 50 minutes or 1.3 mg/kg over 90 minutes) in 15 treatment-seeking 
cannabis-dependent individuals receiving motivational enhancement therapy (MET) and mindfulness-based 
relapse prevention (MBRP) therapy, using a 6-week single-blind, open label trial. 
 
During the first two weeks of study, the participants will receive MET. In Week 2, Day 2, the participants 
will asked to initiate abstinence, and receive a single infusion of ketamine on the day of abstinence 
initiation.  In weeks 3-6, the participants will receive MBRP. If the participants are not doing well, they will 
receive a second infusion of ketamine in Week 4, Day 2. 
 
In addition to measures of mindfulness and impulsivity, stress sensitivity tests are incorporated into the 
design in order to elucidate mechanisms of action. 
 


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Background, Significance and Rationale
Background, Significance and Rationale
This proposal will focus on treating cannabis use disorders with a one or two sub-anesthetic infusions of 
ketamine (0.11 mg/kg 2-min bolus followed by 0.6 mg/kg over 50 minutes or 1.3 mg/kg over 90 minutes), a 
high-affinity non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist.  Our preliminary 
research suggests that ketamine improves dependence-related vulnerabilities common to a variety of 
substances. We have shown that a single infusion improves motivation to quit, reduces cue-induced craving, 
improves non-reactivity, and reduces cocaine self-administration among non-treatment cocaine dependent 
individuals. We have also shown that ketamine infusions can be integrated into outpatient behavioral 
treatment, such as motivational enhancement therapy (MET) and mindfulness-based relapse prevention 
(MBRP), to address cocaine use disorder and alcohol use disorder. This includes a protocol with cocaine 
users  that provides up to 2 ketamine infusions. In these protocols, some individuals who had been using 
cannabis problematically in addition to the substance for which they sought treatment stopped using 
cannabis.
 
In this single blind, open label trial, we extend the treatment model we have developed to treat cocaine use 
disorder to the treatment of cannabis use disorder, with the expectation that we will observe similar 
feasibility. This protocol includes a manualized sequence of MET and MBRP in conjunction with up to 2 
infusions of ketamine. The primary outcome is tolerability of study medications. 
Specific Aims and Hypotheses
Specific Aims and Hypotheses
The primary purpose of this study is to assess whether giving one or two sub-anesthetic dose of ketamine to 
cannabis users will be feasible. 
Description of Subject Population
Sample #1
Specify subject population
Cannabis dependent individuals
Number of completers required to accomplish study aims
15
Projected number of subjects who will be enrolled to obtain required number of completers
20
Age range of subject population


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21-60
Gender, Racial and Ethnic Breakdown
 Based on the demographic distribution of cannabis dependent individuals, we expect that our sample will 
be 45% Caucasian, 25% Hispanic, 25% African American, and 5% other racial groups. Approximately 30% 
of the sample will be female. This profile is also representative of clinical trials at our institution and 
elsewhere targeting cannabis dependent treatment-seeking individuals. This study does not exclude 
participants on the basis of race and gender, and it seeks to include women and minorities 
Description of subject population
Patients will be considered eligible if they are medically healthy, cannabis dependent individuals who meet 
minimum use criteria, who are between the ages of 21 and 60, and who do not have a history of abuse of or 
adverse reaction to ketamine or benzodiazepines. Individuals with physiological dependence on certain 
other substances, with a history of psychotic or dissociative symptoms, with a first-degree family history of 
psychosis, with obesity (BMI > 32), or with cardiovascular or pulmonary disease will be excluded. 
Pregnant women, women who plan to get pregnant, and lactating women will be excluded. 
Recruitment Procedures
Describe settings where recruitment will occur
Adult male and non-pregnant female patients will be recruited in the New York City metropolitan area.
How and by whom will subjects be approached and/or recruited? 
The advertisements that will be used to recruit participants will be submitted to the IRB prior to the 
initiation of recruitment procedures. Additionally, prospective participants are recruited by word of mouth 
and through liaison with other collaborating clinical services, and through ongoing inpatient studies of 
cannabis self-administration conducted at the Substance Use Research Center (SURC) in our division. All 
patients are seen by one of our psychiatrists or staff for a screening evaluation and mental status 
examination as part of routine admission procedures at the BSU. Patients who are cannabis dependent and 
appear to meet criteria are told about the study and offered further evaluation. Final informed consent is 
obtained after full psychiatric and medical workup is complete.
How will the study be advertised/publicized? 
The study will be advertised by newspaper, radio, television, Craigslist, and subway advertisements, as well 
as on a lab-specific website.
Do you have ads/recruitment material requiring review at this time? 
Yes
Does this study involve a clinical trial?
Yes
Please provide the NCT Registration Number
NCT02946489
Concurrent Research Studies


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Will subjects in this study participate in or be recruited from other studies? 
No
Inclusion/Exclusion Criteria
Name the subject group/sub sample
Marijuana dependent individuals
Create or insert table to describe the inclusion criteria and methods to ascertain them
Inclusion Criterion 
1. Meets DSM-IV criteria for cannabis dependence, with at least 5 days of use per week over the past 30 
days and displaying at least one positive utox during screening 
Method of Ascertainment: MINI, psychiatry interview, self-report, utox
 
2. Physically healthy 
Method of Ascertainment: Laboratory tests (urinalysis, blood chemistry, 12-lead ECG within normal limits, 
TB test), physical examination, self-reported medical history
 
3. No adverse reactions to study medications 
Method of Ascertainment: Subjects will be asked about previous exposure to ketamine and midazolam
 
4. 21-60 years of age 
Method of Ascertainment: Self-reported age, verification with legal identification
 
5.Capacity to consent and comply with study procedures
Method of Ascertainment: A short written test about study procedures, MINI, psychiatric interview
 
6. Seeking treatment
Method of Ascertainment: Psychiatric interview, self-report
Create or insert table to describe the exclusion criteria and methods to ascertain them
Exclusion Criterion
1. Meets DSM IV criteria for current major depression, bipolar disorder, schizophrenia, any psychotic 
illness, including substance-induced psychosis, and current substance-induced mood disorder with HAMD > 
12.
Method of Ascertainment: Psychiatric Interview, MINI, HAMD
2. Physiological dependence on another substance requiring medical management, such as alcohol, opioids, 
or benzodiazepines, excluding caffeine, and nicotine
3. Pregnant, interested in becoming pregnant, or lactating
Method of Ascertainment: Blood and urine pregnancy testing, self-report


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4. Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
Method of Ascertainment: MINI, Psychiatric Interview
5. Current suicide risk or a history of suicide attempt within the past 2 years
Method of Ascertainment: MINI, Psychiatric Interview
6. On psychotropic or other medication whose effect could be disrupted by participation in the study
Method of Ascertainment: Psychiatric Interview, self-reported medical history
7. Recent history of significant violence (past 2 years).
Method of Ascertainment: MINI, Psychiatric Interview
8. Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
Method of Ascertainment: Laboratory tests (12-lead ECG in normal limits), physical examination, self-
reported medical history
9. Unstable physical disorders which might make participation hazardous such as end-stage AIDS, 
hypertension (>140/90), anemia, pulmonary disease, active hepatitis or other liver disease (transaminase 
levels < 2-3 X the upper limit of normal will be considered acceptable), or untreated diabetes
Method of Ascertainment: Laboratory tests (urinalysis, blood chemistry, 12-lead ECG in normal limits, TB 
test), physical examination, self-reported medical history
10. Previous history of ketamine or benzodiazepine abuse, and/or a history of adverse reaction/experience 
wtih prior exposure to ketamine or benzodiazepines
Method of Ascertainment: MINI, Psychiatric Interview
11. BMI > 35, or a history of undocumented obstructive sleep apnea
Method of Ascertainment: Physical exam, self-reported medical history
12. First degree relative with a psychotic disorder (bipolar disorder with psychotic features, schizophrenia, 
schizoaffective disorder, or psychosis NOS)
Method of Ascertainment: MINI, Psychiatric Interview
Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization) 
No
Waiver or alteration of consent
Yes
Waiver of documentation of consent 
No
Waiver of parental consent 


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No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol?
No
Describe procedures used to obtain consent during the screening process 
At the first contact, a standardized telephone interview will be conducted, and patients who preliminarily 
meet entry criteria will be scheduled for a first screening visit, during which the patient will give informed 
consent to provide a urine sample for toxicology and urinalysis, and to undergo a Mini International 
Neuropsychiatric Interview (MINI), with a psychiatrist for a medical and psychiatric evaluation, as well as 
completion of the Hamilton Depression Scale (HAM-D) and Dissociative Experiences Scale (DES), and if 
still eligible, with a research assistant for serum collection (CBC, thyroid panel, Chem 20 panel including 
liver function tests, serum cortisol) and other diagnostic tests (EKG). We are requesting a waiver of 
documentation of consent (45 CFR 46.117 (c) (1)) for the phone screen only, given that a consent form for a 
phone screen would be the only record linking the subject and the research.
Describe Study Consent Procedures
Eligible participants will undergo an interview with one of the consenting physicians, during which 
information about the study will be provided. Participants will then be asked to read the consent form on 
their own, after which they complete a quiz and have an opportunity to ask questions. Participants will be 
considered eligible if they are medically healthy, cannabis dependent individuals who meet minimum use 
criteria, who are between the ages of 21 and 60, and who do not have a history of abuse of or adverse 
reaction to ketamine or benzodiazepines. Individuals with physiological dependence on certain other 
substances, with a history of psychotic or dissociative symptoms, with a first-degree family history of 
psychosis, with obesity (BMI > 32), or with cardiovascular or pulmonary disease will be excluded. Please 
consult the full table of inclusion/exclusion criteria in the Human Subjects section for more details. 
Indicate which of the following are employed as a part of screening or main study consent procedures
   Consent Form
Justification for Waiver or Alteration of Consent
Waiver of consent is requested for the following
A waiver of consent has been requested because the first interaction with prospective participants takes 
place over the phone.
Explain why your research can not be practicably carried out without the waiver or alteration
Initial screenings are conducted over the phone, and therefore in-person consent at that point is impossible.  
If a participant is deemed likely to be eligible, he/she is invited into the office for an in-person screening, at 
the start of which formal, in-person consent is obtained. 
Describe whether and how subjects will be provided with additional pertinent information after participation
Subjects are provided with additional pertinent information after participation by the physician.


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Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent
Dakwar, Elias, MD
Levin, Frances, MD
Type in the name(s) not found in the above list
Study Procedures
Describe the procedures required for this study
Design:15 patients meeting study criteria and providing informed consent will be entered into the 6-week 
trial, provided behavioral treatment, and given ketamine. 
At each visit, patients will provide a urine sample that will be tested semi-quantitatively for cannabis and 
other drugs; complete various questionnaires; and undergo a brief evaluation during which vital signs, other 
safety parameters, and side effects are assessed. Two visits a week will be devoted to receiving behavioral 
treatment, lasting approximately 50 minutes. The other regular visit will be with a psychiatrist who will 
review progress, document self-reported substance use, and review side effects or other adverse events to 
treatment; additionally, the psychiatrist is responsible for the medical care of the patient and for decisions 
pertaining to study discontinuation. 
There are two phases: 
Phase 1 (Week 1-2) 
During the first two weeks, patients will receive outpatient motivational enhancement therapy (MET) and 
meet with a psychiatrist twice a week. The psychotherapy sessions be taped for supervision and research 
purposes. 
On Week 2, Day 2, patients will be asked to initiate abstinence 24 hours prior to the medication 
administration. On the day of abstinence initiation, they will receive an intravenous dose of ketamine (see 
“Infusion Procedures”). Before the scheduled outpatient infusion, an MET session will revisit goals and 
address ambivalence. 
Phase 2 (Week 3-6) 
During the last 4 weeks, patients will begin a standardized course of mindfulness based relapse prevention 
(MBRP); this training will occur twice a week, and take approximately one hour a session. Alongside 
MBRP training, patients will meet with a psychiatrist, who will continue monitoring their drug use and side 
effects.
 


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In week 3 or 4, the patients will receive a second intravenous dose of ketamine (see “Infusion Procedures”) 
if they have been unable to attain abstinence.  Before the scheduled infusion, an MET session will revisit 
goals and address ambivalence. 
Infusion Procedures: One or two ketamine infusions will take place at the BSU within the Division on 
Substance Abuse. Further, studies with depression have suggested that a single dose has (antidepressant) 
efficacy. Thus, for the purposes of this study, a single infusion may suffice to affect the outcome measures. 
If it does not suffice, patients will undergo a second infusion. Patients will be abstinent from intoxicants and 
will have not eaten since midnight prior to the infusion so as to reduce the risk of nausea, adverse 
interactions, and aspiration. Participants will be informed throughout the study that they may receive any of 
a number of substances at the infusion, including buspirone, d-cycloserine, ketamine, midazolam, 
memantine, saline, or any combination of these. This will serve to further disguise the administration of 
ketamine, and thereby further minimize the risk that patients will subsequently seek out ketamine. Ketamine 
hydrochloride (0.11 mg/kg 2-min bolus followed by 0.6 mg/kg over 50 minutes for the first infusion and 
1.3 mg/kg over 90 minutes for the second infusion), will be prepared and packaged for slow-drip infusion 
by the pharmacy at NYSPI, and will be administered at 12 pm by a physician. The dose of ketamine was 
selected on the basis of published reports suggesting that it was sub-anesthetic and well-tolerated; it is also 
comparable to the dose used in the depression studies.  Infusions will take place in the presence of an ACLS 
and BLS certified psychiatrist (Dr. Dakwar) who will remain available for up to two hours after the infusion 
is terminated and who will provide a brief safety and psychiatric evaluation at the end of the monitoring 
period. Blood pressure and heart rate will be monitored every five minutes beginning five minutes before 
the infusion and continuing after the infusion until vital signs normalize; SBP elevation > 60 mm and DBP 
> 40, or absolute SBP>200 and DBP>115 and HR > (220 – age) X 0.85, will result in infusion 
discontinuation (please see “Risks” for more information about managing BP or HR). The physician will 
also be responsible for decisions pertaining to the discontinuation of the infusion in the case of an adverse 
event. The physician will also be guiding mindfulness-based exercises for the duration of the infusion. A 
Clinician Administered Dissociative States Scale (CADSS) will be administered following the infusion by 
the physician or the staff. Ketamine and norketamine (an active metabolite) levels will be obtained at 30 
minutes into the infusion and at 60 minutes (20 minutes after the infusion is terminated), the results of 
which will remain unavailable to all staff for each participant until all assessments are complete. The 
infusion will be preceded by a urine toxicology to ensure the absence of illicit substance use to minimize the 
risk of adverse interactions. Female participants will also be tested for pregnancy. Following the infusion, 
participants will undergo close monitoring, and prior to discharge (occurring at least 3 hrs post-infusion) 
psychiatric/medical clearance and a field sobriety test.
Motivational Enhancement Therapy (MET):
 
All patients will receive five MET sessions with a therapist over the first two weeks. Staff involved in MET 
will receive a 3-hour training in MET prior to providing therapy to participants, and a psychiatrist is 
available during all sessions for support or consultation in case it is needed. The psychiatrist will also see 
participants briefly following the therapy session before they go home. Staff will receive weekly supervision 
from the PI for the duration of the trial.
Mindfulness-Based Relapse Prevention (MBRP):


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All patients will have eight MBRP sessions with therapists using a structured MBRP manual adapted for the 
purposes of this study to the individual setting, in collaboration with one of its lead authors, who will also be 
guiding efforts to ensure manual fidelity. Staff involved in mindfulness training receive a 3-hour training in 
MBRP prior to providing training to participants, and a psychiatrist is available during all sessions for 
support or consultation in case it is needed. The psychiatrist will also see participants briefly following the 
mindfulness training session before they go home. Staff will receive weekly supervision from the PI for the 
duration of the trial.
 
 
 
 
 
 
 
 
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any
Criteria for Early Discontinuation  
Criteria for Early Discontinuation
Patients may elect to drop out at any time, and they may be removed by the treating clinicians for clinical 
reasons, including 1) clinically significant worsening leading to an acute psychiatric emergency (e.g., 
suicidality, psychosis, mania), or 2 or more weeks of moderately significant worsening (ascertained by a 
clinical evaluation following 2 weeks of a score of at least 6 or 7 on the CGI improvement scale. A 
score of 6 or 7 would lead to a clinical evaluation and then clinical judgment as to whether the patient 
should be discontinued); 2) inability to comply with study procedures prior to to the 1st infusion; or 3) 
medical complications of treatment. Patients who terminate due to medical or psychiatric problems will be 
offered the necessary level of care (e.g., psychiatric hospitalization for psychosis, inpatient detoxification 
and rehabilitation for worsening drug use). Due to the risks to pregnant women and their unborn 
children associated with these medications, becoming pregnant would result in a participant's early 
discontinuation from the study. 
Blood and other Biological Samples
Please create or insert a table describing the proposed collection of blood or other biological specimens
Two vials of blood will be drawn during the screening process amounting to 10 cc (¾ tbsp). This is to 
determine if there are abnormalities that preclude enrollment into the study. The tests to be run are CBC, 
chem.-20 with LFTs, and b-HCG (for females). During the study, ketamine and norketamine levels will be 
obtained ½ hour into the infusion and 20 minutes after it is terminated; samples are frozen at -20 C and 
packaged in dry ice before being sent to the Nathan Kline lab. These samples will require about 10 cc (1 
tbsp). 
Assessment Instruments
Create a table or give a brief description of the instruments that will be used for assessment
Interviews: Mini International Neuropsychiatric Interview (MINI): A semi-structured diagnostic interview 
designed to assist researchers in making reliable DSM-IV psychiatric diagnoses (45 min); Clinician 
Administered Dissociative States Scale (CADSS): A 23 item clinician administered instrument used to 
measure current dissociative symptoms (5 min); Dissociative Experiences Scale (DES): A 28 item 
questionnaire for assessing the extent of daily dissociative experience, modified to be administered by a 
clinician (5 min); Brief Psychiatric Rating Scale (BPRS) for positive symptoms: A 4 item subscale for 
assessing psychosis (1 min); Hood Mysticism Scale (HMS): a 32 item scale for assessing infusion-
dependent mystical experience, modified to be administered by study staff (5 min); Five Facet Mindfulness 
Questionnaire (FFMQ): A 39 item instrument modified to be clinician administered that assesses five 
mindfulness domains: observing, describing, acting with awareness, non-judging of inner experience, and 


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non-reactivity (5 min); Timeline Follow-Back (TLFB): a retrospective method of quantifying daily 
consumption of alcohol and other drugs, assisted by the maintenance of a weekly use diary (5 min); Barratt 
Impulsiveness Scale (BIS): a 30 item questionnaire used to assess impulsivity, modified to be administered 
by a clinician (5 min); Adverse Symptom Report (ASR): At each visit, the presence, date of onset, or 
resolution of adverse effects will be queried and recorded; Clinical Global Impression Scale (CGI): The CGI 
severity and improvement scales measure the overall clinical status of the subjects and change from 
baseline; Hamilton Depression Scale (HAM-D): A 21 item instrument used to measure current depressive 
symptoms; Treatment Service Review (TSR): A 8 item questionnaire that assesses the recent exposure of 
participants to treatment obtained in the community in excess of what is provided in this protocol; 
Childhood Traumatic Events Scale (CTES): A 6 item semi-structured interview that assesses childhood 
trauma prior to age 17. 
 
Self-Reports: Psychiatric Epidemiology Research Interview Life Events Scale (PERI): A 102 item self-
report that evaluates possible traumas that a participant may have experienced in his/her life in the past 6 
months; Drug-Taking Confidence Questionnaire (DCQ): A validated assessment of self-efficacy; Alcohol 
Abstinence Self-Efficacy Scale: a 40-item assessment that assesses confidence to stop using alcohol in 
various situations (5 min); Perceived Stress Scale (PSS): A 9 item scale that measures levels of subjective 
stress, modified from a monthly assessment to one that evaluates stress between visits (5 min); VAS for 
alcohol craving (VAS-A): A 10 cm long line from “not at all” to “extremely” to assess craving intensity and 
frequency  (1 min). Temperament and Character Inventory (TCI): 240 item questionnaire evaluating 4 
temperament and 3 character dimensions. 
 
Physiological Measures: Blood pressure and temperature.
 
 
 
Please attach copies, unless standard instruments are used
Off label and investigational use of drugs/devices
Choose from the following that will be applicable to your study 
   Drug
Select the number of drugs used in this study
1
Drug #1
Name of the drug 
Ketamine Hydrochloride
Manufacturer and other information
The pharmacy at PI will be supplying the drug.
Approval Status
IND is approved


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IND#
110,464
Who holds the IND/IND sponsor?
IND is held by PI/CU Investigator
Dakwar, Elias, MD
Research Related Delay to Treatment
Will research procedures result in a delay to treatment?
Yes
Maximum duration of delay to any treatment 
The screening process should take about a week, after which eligible participants will be consented and 
provided MET, an effective psychotherapy for cannabis use disorders. Ineligible participants will be 
referred to appropriate treatment. Thus, the maximum duration of delay to treatment is about a week.
Maximum duration of delay to standard care or treatment of known efficacy
 MET and MBRP are evidence-based behavioral treatments for cannabis use disorders that are provided to 
all consenting participants after they complete the screening process. The maximum delay to standard 
treatment is therefore about a week.
Treatment to be provided at the end of the study
All participants will be referred to appropriate evidence-based treatment for substance use disorders, 
including 12-step groups, further psychotherapy, addiction psychiatry, or outpatient rehabilitation, 
depending on the individual
's needs and preferences.
Clinical Treatment Alternatives
Clinical treatment alternatives
Participants not interested in entering this trial will be referred to appropriate treatment for cannabis 
dependence, such as 12-step groups or outpatient/inpatient rehabilitation.
Risks/Discomforts/Inconveniences 
Risks that could be encountered during the study period
The major risk of research participation is related to ketamine administration. Other risks include 
intravenous line placement. 
 
Pregnant and lactating women are especially at risk as the medications used can be harmful to a fetus or 
newborn child as well as the mother herself.
Describe procedures for minimizing risks
1) Ketamine: The dose of ketamine employed in this study was specifically selected because it is equivalent 


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to the dose used with therapeutic effect in other settings, and comparable to doses that have been used safely 
in substance users (alcohol, cannabis, cocaine, opioids) in different protocols at this facility (Protocols 6162, 
6176, 7014, 7051, 7057). Ketamine at the dose used in this study may be associated with a wide spectrum of 
psychological, perceptual and physiological effects. The psychological and perceptual effects include 
depersonalization, derealization, word-finding difficulties, slowed cognition, anxiety, agitation, confusion, 
and sensory changes. Physiological effects at the high dose include dizziness, blurred vision, and nausea. 
Additional side effects of ketamine that are more prominent at higher doses include tachycardia, increased 
blood pressure, sedation, analgesia, incoordination, jaw clenching, transient rash, increased perspiration, 
nystagmus, and fatigue. These effects tend to resolve immediately after the infusion is stopped. Participants 
are informed that they may stop the infusion and/or withdraw from the study at any time. A sitter will be 
present to address any distress that may emerge. In case of outpatient administration, participants will be 
closely monitored post-infusion to assess for persistent effects, and participants will only be discharged after 
3 hrs have elapsed post-infusion and they have passed medical/psychiatric clearance and a field sobriety 
test. 
The sitter, an ACLS certified physician, will also monitor for any side effects. Nausea and vomiting will be 
treated supportively and, if severe, with anti-emetic agents. So as to reduce the risk of nausea, vomiting, and 
aspiration, participants will be NPO after midnight prior to infusions. Anxiety and agitation will also be 
treated supportively and with relaxation exercises. If these side effects do not remit with such measures, 
and/or if the participant persists in asking that the session be stopped, the administration of ketamine will be 
discontinued. In other studies utilizing comparable doses of ketamine infusion, anxiety, psychosis and 
perceptual changes have always spontaneously resolved within 30 minutes of terminating the infusion, often 
within 5 minutes. Intramuscular preparations of midazolam and/or thiothixene will be kept available at the 
central pharmacy in order to rapidly control a ketamine-induced level of emotional distress, psychosis, or 
delirium should it persist. Any participant requiring pharmacotherapy to control a psychiatric complication 
of drug administration will be removed from the study, kept overnight for observation, and given referrals, 
if necessary, the next day, assuming the person can be safely discharged from hospital. 
The administration of subanesthetic ketamine IV also induces a modest rise in vital signs. During the 
ketamine infusion, vital signs (blood pressure and heart rate) will be monitored every five minutes 
beginning five minutes before the infusion begins, and will be monitored after the infusion until baseline 
vital signs are restored. If HR > (220 – patient age) X 0.85 BPM, and if systolic blood pressure increases by 
> 60 mm or diastolic blood pressure increases by > 40 mm (or SBP>200 and DBP>115) during the 
ketamine infusion, the infusion will be permanently discontinued. The blood pressure and heart rate will be 
monitored and if there is no decrease after 5 minutes, then nitroglycerin, clonidine, or propranolol will be 
administered. If high blood pressure is symptomatic, i.e., blurred vision, headache, chest pain, the subject 
will be transferred to the ER.
 
Any medical risks from increased blood pressure will be minimized through the careful screening of 
potential subjects. Subjects will be excluded for baseline hypertension or any history of cardiovascular 
illness. In addition, an ACLS certified physician will be present during the procedure. Continuous ECG 
monitoring and pregnancy testing will be provided, as well.
Extensive laboratory experience suggests that sub-anesthetic ketamine generally produces transient effects 
without any persistent changes, but there are some data suggesting that ketamine, and glutamate modulators 
in general, may alter the glutaminergic system in such a way as to render vulnerable subjects more likely to 


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develop psychotic disorders. Previous studies, therefore, have tended to exclude participants with a personal 
or family history of psychosis in order to reduce the psychiatric risks that ketamine may pose. Accordingly, 
individuals with a personal or first-degree family history of psychosis will be excluded from this study. 
Furthermore, the protocol involves close monitoring and an assessment of psychiatric stability prior to 
discharge; this both ensures that any lingering sedation is allowed to dissipate, and that participants are 
closely monitored for persistent side effects. Participants will be screened by a psychiatrist and cleared for 
continued participation following the infusion on Week 2, Day 2, and they will also be followed twice 
weekly during the following phase of the trial. Subjects will be provided a number to call to reach an on-call 
psychiatrist (24 hours/day) should unpleasant effects occur after subjects have left the testing facility.
 
Ketamine is also associated with some abuse liability, though this abuse liability is significantly lower than 
that of other drugs of abuse, such as cannabis, cocaine, nicotine, alcohol, benzodiazepines, or opioids. 
Ketamine is generally insufflated, ingested, or injected intramuscularly in the community, and is of ten used 
in combination with other substances such as gamma-hydroxy-butyrate (GHB) or 3,4-
Methylenedioxymethamphetamine (ecstasy). There is a risk, therefore, that participants may seek out 
ketamine after becoming exposed to it, and develop problematic patterns of ketamine use during or after the 
study. This risk may be compounded by the fact that it is given in this study to individuals who may have an 
increased vulnerability to developing substance use problems in light of their dependence on cannabis. 
While this important risk cannot be removed entirely, various safeguards can be implemented to ensure that 
it is minimized, including: 1) exercising “a minor deception” and giving participants the impression that 
they may receive any of a number of medications during each infusion, while ensuring that the side effects 
and risks are clearly conveyed; this may prevent patients from identifying ketamine and subsequently 
seeking it out; 2) excluding participants with a history of ketamine misuse or abuse; and 3) carefully 
monitoring drug use to ensure that any emergent patterns of misuse or abuse of ketamine, or any other 
substance, is properly addressed in a timely manner. Futhermore, ketamine is administered in this study in a 
way that is unrepresentative of how it is commonly used in the community (slow-drip IV infusion). In 
addition, this slow, sustained method of administration is unlikely to lead to the acute powerful effects 
generally associated with heightened abuse liability.
 
Participants who develop a significant adverse reaction during or after the infusion (psychosis, agitation, or 
adverse psychological response that is persistent and/or requiring pharmacotherapy; blood pressure 
elevation requiring termination) will lead to the blind being broken. This will alert the participant to his or 
her propensity for an adverse response to the drug, thus ensuring future safety.
There is a risk of adverse interactions with the study medications if participants are actively intoxicated on 
illicit medications. In order to minimize this risk, participants are encouraged to remain abstinent before the 
infusion, and will be tested daily with urine toxicology. They will also undergo a field sobriety test on the 
day of the infusion, prior to administration. In addition, they will be evaluated by a clinician (Dr. Dakwar) 
for DSM-IV signs of any intoxication.  
In conclusion, the careful evaluation of participants during the screening process for cardiovascular, 
psychiatric, medical, and historical vulnerabilities to ketamine infusion; the presence of a psychiatrist with 
ACLS certification (the PI) during and after the infusion who will monitor for side effects and adverse 
events; the sub-anesthetic, generally well-tolerated dose at which ketamine will be infused; the close 
monitoring during infusion; the psychiatric evaluation and clearance to go home; the regular outpatient 
visits to monitor for persistent effects; and the provision of supportive and pharmacological measures to 


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address any side effects all ensure that the medical and psychiatric risks involved in participation in this 
study will be minimal.
2. Blood drawing/Intravenous placement: Another risk in the study is that bruising or a blood clot could 
form at the site of the intravenous line or venipuncture. Medical staff with extensive experience with IV 
placement will remain available to ensure that risks are minimized. 
 
In order to safeguard against risks towards pregnant women, evaluation will be conducted on whether the 
risk of treatment is acceptable for women of childbearing potential. Staff will discuss with participants the 
risks associated with participation and the importance of adequate birth control practice.  In addition, staff 
will evaluate whether the participant is willing and reliable to practice effective birth control during the 
study. Urine pregnancy testing will be conducted at baseline evaluation and on a weekly basis throughout 
the course of the study. Staff will periodically discuss with patients to review importance of not becoming 
pregnant, and adequacy of birth control practices (all of which will be documented). As the testing methods 
used have limitations, participants will be encouraged to inform the research staff if they believe they have 
become pregnant so that the safety of the participant can be ensured.  As the risk towards pregnant women 
outweighs the benefits of participating in this study, if a participant becomes pregnant during the course of 
the study, they will be discontinued from their participation.
 
 
Methods to Protect Confidentiality
Describe methods to protect confidentiality
A Certificate of Confidentiality will be acquired for this study from the National Institute on Drug Abuse to 
offer protection for the privacy of subjects by protecting identifiable research information from forced 
disclosure (e.g., through a subpoena or court order). The Certificate of Confidentiality allowed investigators 
and others with access to research records to refuse to disclose information that could identify subjects in 
any civil, criminal, administrative, legislative, or other proceeding, whether at the Federal, State, or local 
level. The Certificate of Confidentiality is granted for studies that collect information that, if disclosed, 
could damage subjects’ financial, employability, insurability, or reputation, or have other adverse 
consequences. 
We use coded records (i.e. initials and numbers), store signed consent forms in a locked room, and try, to 
the best of our ability to maintain confidentiality. Only coded records will be entered into the computer and 
the security of electronic data is ensured at the level of the server, the user, and the database. We do, 
however, point out to prospective patients, that we cannot assure that their drug histories and other personal 
records might not become known.
Will the study be conducted under a certificate of confidentiality?
Yes, we will apply for the Certificate of Confidentiality


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Direct Benefits to Subjects  
Direct Benefits to Subjects
All patients will receive MET and MBRP. MET has been found to be effective in treating Cannabis Use 
Disorder (Dennis et al., 2004; Nordstrom & Levin, 2007; Sellman et al., 2001), and MBRP has been 
shown to be effective to preventing cannabis dependence relapse (Grant et al., 2015)
Compensation and/or Reimbursement 
Will compensation or reimbursement for expenses be offered to subjects?
Yes
Please describe and indicate total amount and schedule of payment(s). 
Include justification for compensation amounts and indicate if there are bonus payments.
 
Participants will be given $10 for each visit to cover the costs of travel, which they will receive each day that they 
come. Participants will also be compensated with $25 on the days of medication administration. Taking into account 
screening visits, participants may earn up to $195.
References
References
Dennis, M., Godley, S. H., Diamond, G., Tims, F. M., Babor, T., Donaldson, J., ... & Hamilton, N. 
(2004). The Cannabis Youth Treatment (CYT) Study: main findings from two randomized trials. 
Journal of substance abuse treatment, 27(3), 197-213.
Grant, S., Hempel, S., Colaiaco, B., Motala, A., Shanman, R. M., Booth, M., ... & Sorbero, M. E. 
(2015). Mindfulness-Based Relapse Prevention for Substance Use Disorders.
Nordstrom, B. R., & Levin, F. R. (2007). Treatment of cannabis use disorders: a review of the 
literature. American Journal on Addictions, 16(5), 331-342.
Sellman, J. D., Sullivan, P. F., Dore, G. M., Adamson, S. J., & MacEwan, I. (2001). A randomized 
controlled trial of motivational enhancement therapy (MET) for mild to moderate alcohol 
dependence. Journal of Studies on Alcohol, 62(3), 389-396.
Uploads


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Dakwar, Elias
Page 19 of 19
Upload the entire grant application(s)
Upload copy(ies) of unbolded Consent Form(s)
Upload copy(ies) of bolded Consent Form(s)
Upload copy(ies) of recruitment materials/ads to be reviewed
7355 CL ad 20180521.pdf
7355 Ad.pdf
Upload evidence of FDA IND approval(s)
Upload copy(ies) of the HIPAA form
7355 HIPAA.pdf
Upload any additional documents that may be related to this study


Are you ready to stop using marijuana?
The Substance Use Research Center at the Columbia University Medical 
Center/New York State Psychiatric Institute is seeking marijuana users who 
wish to participate in a treatment study.
 
We are looking for healthy men and non-pregnant women between the ages of 
21 and 60 years old who are seeking to reduce or stop cannabis use. 
Participants will receive medication and free, weekly individual psychotherapy 
for the duration of the 6-week study period. Twice weekly clinic visits are 
required at Columbia University Medical Center; travel compensation is 
provided for participation.
Please reply to this post with your phone number or call us at 888-497-8427.
For more information, please visit our website: newyorkaddictiontreatment.org




Form #PP2: HIPAA Authorization for Research 4.14.14 
New York State Psychiatric Institute (NYSPI) 
Authorization to Use or Disclose Health Information during a Research Study 
Protocol Number: 
Principal Investigator: 
Name of Study: 
Before researchers can use or share any identifiable health information (“Health Information”) about you as part of the 
above study (the “Research”), the New York State Psychiatric Institute (NYSPI) is required to obtain your authorization. You agree 
to allow the following individuals and entities to use and disclose Health Information about you as described below: 
• New York State Psychiatric Institute (NYSPI), your doctors and other health care providers, if any, and
• The Principal Investigator and his/her staff (together “Researchers”).   Researchers may include staff of NYSPI, the New York
State Office of Mental Health (OMH), Research Foundation for Mental Hygiene, Inc. (RFMH), and Columbia University (CU),
provided such staff is a part of the study, and
•
Providers of services for the Research at CU, NYSPI and/or RFMH, such as MRI or PET, or  Central Reference Laboratories 
(NKI), if indicated in the consent form.
1.  The Health Information that may be used and/or disclosed for this Research includes:
All information collected during the Research as told to you in the Informed Consent Form.   
Health Information in your clinical research record which includes the results of physical exams, medical and 
psychiatric history, laboratory or diagnostic tests, or Health Information relating to a particular condition that is related  to 
the Research. 
Additional information may include: 
2. The Health Information listed above may be disclosed to:
Researchers and their staff at the following organizations involved with this Research: 
The Sponsor of the Research, 
and its agents and contractors (together, “Sponsor”); and  
Representatives of regulatory and government agencies, institutional review boards, representatives of the Researchers 
and their institutions to the level needed to carry out their responsibilities related to the conduct of the research.   
Private laboratories and other persons and organizations that analyze your health information in connection with 
this study 
Other (family members or significant others, study buddies, outside agencies etc.) Specify: 
3. By giving permission to release your Health Information as described above, you understand that your Health
Information may be disclosed to individuals or entities which are not required to comply with the federal and state privacy laws
which govern the use and disclosure of personal Health Information by NYSPI.   This means that once your Health
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Elias Dakwar, MD
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Substance Use Research Center, New York State Psychiatric Institute 
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Elias Dakwar, MD
Glutamatergic Modulation to Facilitate the Behavioral Treatment of Cannabis 
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Substance Use Research Center, New York State Psychiatric Institute 
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Substance Use Research Center, New York State Psychiatric Institute 
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Glutamatergic Modulation to Facilitate the Behavioral Treatment of Cannabis 
Elias Dakwar, MD
7355


Form #PP2: HIPAA Authorization for Research 4.1.14 
Information has been disclosed to a third party which does not have to follow these laws (e.g., a drug company or the Sponsor 
of the Research), it may no longer be protected under the HIPAA or NYS Mental Hygiene Law requirements but is subject to the 
terms of the consent form and may be subject to other state or federal privacy laws or regulations.  
4. Please note that:
• You do not have to sign this Authorization form, but if you do not, you may not be able to participate in the study or
receive study related care.  You may change your mind at any time and for any reason. If you do so, you may no
longer be allowed to participate in the study.  If you withdraw this Authorization the research staff and the Sponsor, if this
is sponsored research, may still use or disclose Health Information containing identifying information they already have
collected about you as needed to maintain the reliability of the research.  Any request to withdraw this Authorization
must be made in writing to (enter name and contact information below):
• While the Research is going on, you may not be allowed to review the Health Information in your clinical research
record that has been created or collected by NYSPI.   When this research has been completed you may be allowed to see
this information.  If it is needed for your care, your Health Information will be given to you or your Doctor.
5. This Authorization does not have an end date.
6. You will be given a copy of this form after you have signed it.
I agree to the use and disclosure of Health Information about me as described above: 
__________________________________________                _____________________ 
Signature of Participant/ Legal Representative     
Date 
______________________________________ 
Printed Name of Participant 
______________________________________ 
Relationship of Legal Representative to Participant (if applicable) 
We also ask you or your legal representative to initial the statements below: 
I have received a copy of the NYSPI/OMH Notice of Privacy Practices. 
Elias Dakwar, MD, 1051 Riverside Drive, Unit 66, New York, NY 10032
Elias Dakwar, MD, 1051 Riverside Drive, Unit 66, New York, NY 10032
Elias Dakwar, MD, 1051 Riverside Drive, Unit 66, New York, NY 10032