Effect of Lorcaserin on Cannabis Withdrawal and Self-administration
Phase: PHASE1
Conditions: Cannabis Use
Sponsor: New York State Psychiatric Institute

Uploaded Protocol Summary Form 
 
Cover Page 
Background, Significance, and Rationale 
 
 
 
 
 
Protocol Number: 7475 
Version Date: 6/12/18 
Protocol Title: Effect of Lorcaserin on Cannabis Withdrawal and Self-administration 
Principal Investigator: Margaret Haney, PhD 
Email: mh235@cumc.columbia.edu 
Telephone: 646-774-6153 
Office: 
Cell 
NCT03253926 
 
 
 
 
This section is intended to provide a basic overview of the study including a description of its purpose, methods, and 
subject population. The summary should provide a concise overview of the study for non-scientific and scientific 
members of the IRB. Please avoid medical or technical terminology. In general, the abstract of a grant does not provide 
a suitable lay summary. 
Please also paste of a copy of the Lay Summary into the PRISM PSF Form. 
 
In order to improve treatment outcome for cannabis use disorder (CUD), we have developed a laboratory model to 
investigate the effects of potential treatment medications on cannabis withdrawal and on the subjective and reinforcing 
effects of cannabis in non treatment-seeking, cannabis smokers. In this study, we are interested in testing how 
lorcaserin (10 mg, BID) influences the effects of cannabis and the choice to smoke cannabis in this human laboratory 
model of cannabis administration. Lorcaserin is a well tolerated, selective 5HT2c agonist that is FDA-approved for the 
treatment of obesity. 5HT2c receptors are abundant in areas rich in dopamine neurons (Abramowski et al., 1995) and 
are involved in modulating impulsive behaviors and reactivity to drug-related cues (Anastasio et al., 2013; Cunningham 
and Anastasio, 2013). Recent preclinical data show that lorcarserin reduces THC self-administration and relapse in non- 
human primates (Justinova et al., unpublished). We hypothesize that lorcaserin will decrease cannabis withdrawal 
symptoms and cannabis relapse in this human laboratory model. 
 
In this section, provide a brief summary of the status quo of the relevant work field, and how the proposed study will 
advance knowledge. Specifically, identify the gaps in knowledge that your project is intended to fill. If no gaps exist that 
are obviously and directly related to your project, explain how your proposed research will contribute to the overall 
understanding of your field. Describe potential impacts of your project within your field of study and in a broader context. 
Provide a critical evaluation of existing knowledge. The literature review does not have to be exhaustive. 
 
Cannabis use is increasing (SAMHSA, 2012) and numbers are likely to rise further with legalization; residents of states 
with medical cannabis laws have higher odds of cannabis use and higher rates of DSM-V abuse/dependence compared 
to states without these laws (Cerdá et al., 2012). Almost 20% of patients entering treatment for substance use disorders 
have a diagnosis of cannabis use disorder (CUD; SAMHSA, 2013), yet their outcome is poor. Only 15%–37% of patients 
achieve continued abstinence from cannabis following clinical treatment (MTPRG, 2004; Budney et al., 2006; Kadden et 
al., 2007; Levin et al., 2011). There is a clear need for FDA-approved pharmacological options to improve cannabis 
Lay Summary 

Uploaded Protocol Summary Form 
 
 
 
treatment outcomes. Human laboratory studies provide a powerful means of investigating potential medications for 
drug treatment, and are an important precursor to guide expensive clinical trials (Koob et al., 2009). 
 
The overall aim of this study is to test the effects of lorcaserin on a range of clinically-relevant behaviors: cannabis self- 
administration under non-abstinent conditions, relapse to cannabis use, mood, sleep, food intake, and cognitive task 
performance. This drug is of interest because 5HT2c agonists influence behaviors motivated by a wide range of 
reinforcers. In preclinical studies, 5HT2c agonists, including lorcaserin, reduce the stimulant, discriminative stimulus and 
reinforcing properties of nicotine, ethanol and cocaine, as well as reinstatement of nicotine and cocaine seeking 
(Grottick et al., 2000; Fletcher et al., 2012; Cunningham et al., 2011; Higgins et al., 2013; Collins et al. 2016). These 
effects persisted with repeated medication administration (e.g., Yamauchi et al., 2004), essential for a treatment 
medication. Similar to obesity, the indication for which lorcaserin is approved, substance use disorders reflect learned 
behaviors that persist despite negative consequences (e.g., Bickel et al, 1999; Fields et al., 2009). Lorcaserin is currently 
in clinical testing as an aid for smoking cessation (ClinicalTrials.gov: NCT02044874) and a treatment for cocaine-use 
disorder (studies NCT02680288, NCT02537873). 
 
In non-human primates, pretreatment with 5-HT2c agonist lorcaserin dose-dependently reduced THC self-administration 
behavior at a dose (4 μg/kg/inj.) that maintains high rates of drug taking behavior. In a model of relapse, lorcaserin also 
dose-dependently reduced cue-induced reinstatement of previously extinguished THC-seeking behavior. However, 
lorcaserin did not affect THC priming-induced reinstatement. At the doses that affected THC self-administration and 
reinstatement, lorcaserin did not reduce food-maintained self-administration under the same schedule of reinforcement 
(Justinova, unpublished data). These findings suggest that lorcaserin could be a novel treatment for CUD. 
 
 Specific Aims and Hypotheses 
 
Concisely state the objectives of the study and the hypothesis or primary research question(s) being examined. There 
should be one hypothesis for every major study procedure or intervention. For pilot studies, it is important not to 
overstate the study's objectives. If there are no study hypotheses, describe broad study goals/aims. 
 
The overall aim is to test the effects of lorcaserin on a range of clinically relevant behaviors: cannabis self- 
administration, relapse to cannabis use, mood, sleep, food intake, and cognitive task performance. We hypothesize that 
lorcaserin will attenuate cannabis’ positive subjective effects and facilitate abstinence initiation, i.e., reduce cannabis 
self-administration under non-abstinent conditions, as well as reducing relapse to cannabis use. 
 
Inclusion/Exclusion Criteria 
 
This section details your study sample(s) and addresses the requirement for risk minimization. 
You may choose to divide your sample by population (healthy controls vs. subjects) or by procedure (subjects who will 
have an MRI) and then define different sets of criteria for each. 
For each sample, create or insert a table to describe detailed criteria for study inclusion and exclusion and the method 
you will use to ascertain each criterion. The method of ascertainment may describe tests, scales and instruments. When 
relevant, indicate the level of training of the person who will make the assessment (e.g. clinical interview by a 
psychiatrist). 
Inclusion/Exclusion Criteria needs to be numbered and listed in outline form (see Table template below). 
 
Name the subject group/sub sample 
Healthy Cannabis Smokers 

Uploaded Protocol Summary Form 
 
 
CRITERION 
METHOD OF ASCERTAINMENT 
Inclusion: 
1. Current cannabis use: average of 2 
cannabis cigarettes per day at least 6x/ week 
for the past 4 weeks 
Self-report during clinical interviews (telephone, 
psychologist, physician), urine toxicology 
2. Able to perform study procedures 
Practice sessions, physician’s physical and 
mental status examination 
3. 21-50 years of age 
Legal identification 
4. Women practicing an effective form of 
birth control (condoms, diaphragm, birth 
control pill, IUD) 
Self-report during clinical interview, physician’s 
evaluation 
5. English Speaking 
Clinical interview, ability to complete screening 
paperwork 
6. Able to give informed consent 
Clinical interview, physician’s mental status 
examination 
Exclusion: 
1. Current diagnosis of an eating disorder 
(anorexia, bulimia, etc.) or have lost more 
than 10% of their body weight within the last 
3 months and a known sensitivity, allergy or 
contraindication to lorcaserin or similar 
medications 
Medical history, physical examination 
2. Current, repeated (>2x/week) illicit drug 
use other than cannabis 
Clinical interview, physicians evaluation, urine 
toxicology 
3. Presence of any clinically significant 
cardiovascular, respiratory, renal, 
gastrointestinal, hematologic, neurologic, 
pulmonary, immunologic, hepatic, endocrine, 
or other abnormality 
Medical history, physical examination, 12-lead 
ECG, laboratory tests (Chem panel, CBC, 
urinalysis) 
4. History of heart disease and cardiac risk 
factors (congestive heart failure, edema, 
unstable angina, or cardiac arrhythmias), 
blood pressure > 140/90, severe chronic 
obstructive pulmonary disease, uncontrolled 
hypertension or diabetes, or other medical 
condition that would make participation 
hazardous 
Self-report, clinical interview, abnormal ECG, 
Medical history, physical examination 
5. Interest in treatment for cannabis use 
Self-report, clinical interview 
6. Current parole or probation 
Self-report, clinical interview 
7. Current pregnancy or lactation 
Clinical interview, physical examination, 
pregnancy testing (serum HCG) 

Uploaded Protocol Summary Form 
 
 
8. Recent history of significant violent 
behavior (past year) 
Self-report, clinical interview 
9. Current Axis I psychopathology requiring 
medical intervention (e.g., bipolar disorder, 
major depressive disorder, suicide risk, 
schizophrenia) 
Clinical interview; diagnoses determined by a 
clinical interview via the SCID, as confirmed by 
the psychiatric evaluation 
10. Current use of any prescription or over- 
the-counter medication 
Clinical interview, medical history, physical 
examination 
 
 
Study Procedures 
 
Provide a clear, concise narrative of study procedures with special attention to the subjects' involvement. Detail the 
overall study timeline and location of study procedures, list all interventions, assessments and interviews, estimate the 
duration of each procedure, provide dosing schedules, identify study personnel involved in each procedure, and provide 
credentials for relevant personnel. For complicated study designs, we strongly encourage attaching tables, flow-charts, 
and study algorithms. 
 
General design: This within-subject study will have two 11-day inpatient phases, with one phase testing lorcaserin and 
the other phase testing placebo maintenance in counter-balanced order. In between the two inpatient phases, there will 
be a minimum 7-day outpatient period with no medication administration to provide time for medication clearance and 
the resumption of daily cannabis use. Inpatient phases will be preceded by two brief outpatient days of lorcaserin 
administration and a move-in day so that by Day 1 of each inpatient phase, participants will have achieved steady state 
conditions (3 days of 10 mg BID lorcaserin administration). On outpatient dosing days, participants will take their AM 
capsule under observation and will take their PM capsule (2030) at home. On the third day (move-in day), they will take 
their AM capsule under observation and then receive their PM capsule after moving into the laboratory. While inpatient, 
AM and PM capsules will always be administered under observation. 
 
Outpatient Dosing Visits: Participants will undergo two outpatient dosing visits immediately prior to each inpatient 
phase. On outpatient dosing days, participants will be administered capsules (lorcaserin or placebo, depending on 
phase) at 0900 under observation and will take their PM capsule (2030) at home. During outpatient dosing visits and 
move-in day, research staff will measure vital signs, urine toxicology, conduct at Timeline Followback and document any 
reported side effects from the medications. Staff will also ask about any medication or dietary supplement use. 
Participants will move into the residential laboratory (NYSPI, Division on Substance Use) the morning of the third 
outpatient dosing visit. They will be given the option to contribute a DNA sample on move-in day. We will over-enroll 
during the first outpatient phase, starting up to 7 individuals on medication, in order to ensure that we will have the 
maximum number of participants that can stay in the residential laboratory (n=4) on move-in day. 
 
Inpatient Phase: Immediately before the onset of each new medication phase, female participants will have a urine 
pregnancy test. The overall design and daily inpatient schedule is outlined in the attached tables (Table 1 and 2). We will 
assess vital signs each morning. On move-in day, we will instruct participants on how to smoke marijuana using the 
paced puffing procedure and will inform them that this is the strength available for self-administration. On the first full 
inpatient day (day 1), participants will smoke experimenter-administered cannabis 6 times (3 puffs/occasion). The 
purpose of this day is to standardize cannabis exposure prior to abstinence initiation. During the next 3 days (days 2-4; 
Table 1), participants will have the opportunity to purchase individual puffs of cannabis at $2/puff, at 6 time points. This 
measures the reinforcing effects of cannabis under nonabstinent conditions, and will reveal whether a medication 
facilitates abstinence initiation. On day 5, cannabis will be experimenter administered at 6 time points in order to again 
standardize cannabis exposure and assess medication effects on cannabis subjective ratings. On days 6-8, no cannabis 

Uploaded Protocol Summary Form 
 
 
 
 
will be available. This period will assess medication effects on cannabis withdrawal. For the remaining inpatient days 
(days 9-11; Table 1), participants will be presented with 6 opportunities throughout the day to purchase individuals puffs 
of cannabis ($7 first puff, $1 subsequent puffs). These days provide a laboratory measure of cannabis relapse. Money 
spent on cannabis during the inpatient phase is deducted from the total study pay at the end of the study. Participants 
will move out on Day 12 after passing the field sobriety test. Note, we will counter-balance the cannabis self- 
administration and relapse conditions across inpatient phases so participants are not able to predict the study schedule 
in the subsequent inpatient phase; sometimes the withdrawal and relapse condition will occur first and the abstinence 
initiation condition will occur second. Throughout each day, participants will wear an Actiwatch Activity Monitoring 
System (Actiwatch: Respironics Company, Bend OR), which tracks gross motor activity, and provides objective data on 
the number of hours slept and the number of awakenings (Perez et al., 2008). The Actiwatch is the size of a wristwatch. 
It will be removed briefly each evening in order to download that day’s data. Participants will also give a urine sample 
each morning upon awakening. We will conduct a urine toxicology twice/week; we will also measure extracellular 
vesicles in urine on certain inpatient days to look for biomarkers of recent marijuana use (potential preliminary data for 
future grant funding). 
 
 
Table 2: Inpatient Schedule 
0815 Wake up 
1315 
Task and Subjective-effects Batteries 
Subjective-Effects Battery 
1415 
Choice of 0, 1, 2, or 3 puffs 
Sleep questionnaire 
1430 
Cannabis administration 
Tobacco Cigarettes 
1445 
Task and Subjective-effects Batteries 
Weigh In, BP/HR Receive Food Boxes 
1545 
0830 Medication administration 
1600 
Choice of 0, 1, 2, or 3 puffs 
Cannabis administration 
0900 Task and Subjective-effects Batteries 
1615 
Task and Subjective-effects Batteries 
0945 Choice of 0, 1, 2, or 3 puffs 
1700 
Recreation period starts 
1000 Cannabis administration* 
2030 
Medication administration 
1030 Task and Subjective-effects Batteries 
2145 
Choice of 0, 1, 2, or 3 puffs 
1115 Choice of 0, 1, 2, or 3 puffs 
2200 
1130 Cannabis administration 
Recreation period ends 
Cannabis administration 
Subjective-Effects Battery 
 
 
*On experimenter-administered days, participants will not be required to purchase puffs but will be given cannabis at 
no cost at the 6 times indicated. On self-administered days, cannabis will only be administered if participants choose to 
purchase it. All medication administration is double-blind. 
 
 
Debriefing: Participants spend the morning after completion of the final inpatient phase being debriefed regarding the 
study design. Participants are encouraged to ask questions and provide recommendations for improving the experience 
(e.g., food, movies, computer games). Following debriefing, the investigator will discuss options for cannabis treatment, 
1245 Choice of 0, 1, 2, or 3 puffs 
2400 
Lights out 
1300 Cannabis administration 
1215 Task and Subjective-effects Batteries 

Uploaded Protocol Summary Form 
 
 
 
and will give participants a pamphlet for our clinic (STARS), where cannabis-specific treatment studies are underway. It 
will be emphasized that treatment is always an option, they can always contact us for referral information, or call STARS 
directly, if they are ready to stop smoking cannabis. We are careful to only enroll non-treatment seekers into our 
studies, so it is unusual for participants to express interest in treatment. However, the investigator will emphasize that 
treatment for cannabis use may be of interest in the future. We will also do a 12-lead ECG on the final study day. 
Participants will not leave the laboratory until a study physician approves the ECG. 
 
Criteria for Early Discontinuation 
 
Define criteria that will be used to exit or drop subjects from the study. Indicate the time points when such criteria will be 
applied, and describe the rating instruments, parameters, and thresholds that will lead to a decision to terminate a 
subject's participation. In addition, explain procedures for managing subjects who are dropped from the protocol. 
For treatment studies: To minimize risks to subjects, operationalized drop-out criteria should be defined so that subjects 
who worsen, or in some cases, fail to improve, are removed from the study and offered standard care. The threshold for 
drop-out should consider the level of risk associated with non-improvement for the specific disorder, the availability of 
alternatives, and the typical required duration of treatment. For example, emergence of suicidal intent, or psychosis, 
should prompt immediate clinical evaluation and withdrawal from the study. 
 
Participants will be removed from the study and assessed by a member of the clinical staff if, at any stage during 
participation, they: 1) experience a panic attack, as diagnosed by DSM-V criteria; 2) experience significant psychological 
deterioration as indicated by self-reported anxiety or depressed mood producing clinically significant distress beyond 
the discomfort typically experienced during cannabis withdrawal; 3) report suicidal ideation; or 4) show functional 
deterioration as indicated by inability to comply with study procedures or erratic or aggressive behavior. Experienced 
research staff will monitor participants for any potential medical or psychiatric issues over the course of the study in 
concert with the medical director, Dr. Frances Levin. If a patient is removed from the protocol, clinical staff will 
undertake a risk assessment and determine the appropriate course of action, including but not limited to admittance to 
the emergency department of Columbia University Medical Center, and referral for outpatient treatment. Participants 
may also be discontinued if they fail to follow the study procedures. 
 
Blood and other Biological Samples 
 
Describe how the sample will be used and indicate, when relevant, the amount of the sample. The IRB wants to know 
that the sample is sufficient for the purposes of the study, but that sampling is limited to what is minimally necessary. 
If you’ve indicated that you intend to store a sample for future use, indicate where the sample will be stored, how long 
the sample will be stored, and to what purposes the sample will eventually be put. Check the IRB website at 
http://irb.nyspi.org/irbdnn/Policies/GeneticResearch/tabid/96/Default.aspx for specific guidance and additional 
information about future use of DNA samples. 
 
We will do a complete blood chemistry and a plasma pregnancy test (15 ml blood) at screening. If participants opt to 
participate in the genetics study (IRB #6929R), and if we collect blood rather than buccal samples, an additional 15 ml 
may be drawn on an inpatient study day, totaling up to 30 mls. 
 
The collection of DNA/RNA will enable direct study of possible genetic contributions to both the patterns of behavioral 
response and biological measures associated with both illness and health. These samples will be used to investigate 
genetic contributions to drug use, abuse, and dependence. Although the focus of the research is on the study of 
addiction, we ask participants to indicate in their consent form whether they would also allow their DNA to be used for 
research on other (unforeseen) disorders. The measurement of DNA is optional, and it will be made clear to individuals 
that they are not required to volunteer for this component in order to participate in the main studies. Blood, cheek swab 

Uploaded Protocol Summary Form 
 
 
 
or saliva samples will be de-identified by Dr. Haney. Blood plasma (2 ml) and saliva samples will be will be stored at -80 
°C until they are shipped out for analysis. Dr. Haney will code samples with an ID number and have sole access to the 
codes. The samples will be sent to Dr. McGeary at Brown University or to Dr. Regina Santella of the Biomarkers Shared 
Resource center of Herbert Irving Comprehensive Cancer Center of CUMC with the accompanying ID number, age and 
gender. Drs. John McGeary and Santella has agreed to collaborate with us on these studies. They will not have access to 
any identifying information including the name, birthday, social security number, telephone number, or address of the 
participant. Once the samples are sent to the Biomarkers Shared Resource center or to Brown University, they will be 
stored in a repository to which only Drs. McGeary and Santella and his staff will have access. Cell lines will not be grown 
from the samples. Once the RNA and DNA has been extracted from the samples and analyzed for polymorphisms and 
biomarkers of interest, the data will be sent to Dr. Haney with the accompanying serial number. 
 
Assessment Instruments 
 
List all assessment instruments, indicate who will administer them, and provide an estimate the duration of each. The 
IRB wants to know that assessments instruments are appropriate measures for the purposes of the study and are no 
more burdensome than is necessary. The IRB will consider the burden of assessment instruments (in terms of time, 
sensitivity of material, etc.) in the risk/benefit analysis. Please attach copies or otherwise provide all non-standard 
instruments. 
 
Screening Instruments: 
Telephone Interview: 10 min 
Drug Use History Questionnaire: 10 min 
General Health Questionnaire: 5 min 
Medical History Questionnaire: 10 min 
Beck Depression Inventory: 5 min 
Barratt Impulsiveness Scale: 10 min 
Trauma Assessment for Adults: 5 min 
Michigan Alcoholism Screening Test (MAST): 5 min 
Physical and Psychiatric Examination: 30 min 
Laboratory Tests: 30 min 
PhD Interview (MINI SCID and drug use history interview): 30 min 
 
Objective Sleep Measures: Participants will wear an Actiwatch Activity Monitoring System that tracks gross motor 
activity (Actiwatch®: Respironics Company, Bend, OR; Kushida et al., 2001) 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 (e.g., Haney et al., 2010, 2013b). 
 
Subjective Effects: A 3-minute series of visual analog scales (VAS) in which participants indicate how they are feeling at 
that moment will be done 8 times/day. Mood states including symptoms of cannabis withdrawal (e.g., I feel irritable), 
positive subjective effects (e.g., I like the cannabis), medication effects (e.g., I feel sedated) and drug craving (e.g., I want 
to smoke cannabis) are assessed. In addition, subjective ratings of the previous night’s sleep are measured each 
morning. 
 
Tobacco Cigarette Smoking: Cigarette-smoking participants will be provided with cigarettes and a lighter upon request. 
They will report each cigarette prior to smoking it by scanning it with a bar code scanner. At the end of each day, the 
number of cigarettes smoked will be verified by removing and counting the remaining cigarettes and butts. Cigarette use 
is an important predictor of cannabis relapse (Haney et al., 2013a). 
 
Performance Battery: A 25-minute battery, comprising a Digit-Symbol Substitution Task, Divided Attention Task, Rapid 
Information Processing Task, Repeated Acquisition Task, and an Immediate and Delayed Memory Task (see Foltin and 

Uploaded Protocol Summary Form 
 
Research Related Delay to Treatment 
Clinical Treatment Alternatives 
Risks/Discomforts/Inconveniences 
 
 
Evans, 1993) will be completed 6 times/day. The battery assesses subtle changes in mental acuity, learning, and working 
memory, which could impact the medications’ practical utility in the clinic. 
 
Self-Report Questionnaires: 
Drug Effects Questionnaire: 1 min Cannabis Rating Form (MRF): 2 min State Anxiety Inventory: 1 min 
Visual Analog Craving Scales (CAS): 3 min Beck Depression Inventory: 5 min 
 
Food Intake: A wide range of food items are available ad libitum. Participants scan each item with a bar code scanner 
before consumption, which tracks timing as well as caloric and macronutrient content. 
 
Additional Behavior: Social Behavior 
 
Physiological Measures: 
Qualitative Urinalysis: Collected daily; analyzed biweekly 
ActiwatchTM: Worn daily, measures activity 
ECG at study termination, heart rate and blood pressure daily 
 
Research involving participants who are in need of treatment invariably involves delay to care, and this delay is 
associated with risk. Scheduling of procedures must be carefully organized to minimize delay. Other delay must involve 
only that minimally necessary to accomplish the aims of the research while respecting subject well- being and safety. 
Describe the delay, by virtue of research participation in this study, before a participant can receive treatment of known 
efficacy or standard care routinely offered in the community. 
 
Research procedures will not result in a delay to treatment since participants are not seeking treatment for cannabis 
use. Nonetheless, all will be informed of cannabis treatment at STARS in case they change their minds in the future. 
 
Describe what other treatment or assessment options are available to subjects who do not participate in research. 
 
Participants are not seeking treatment. The alternative is to not participate in this study. 
 
"Risk" is a broad term used to convey the potential for harm, burden, and inconvenience related to research 
participation. Use this section to provide a comprehensive description of foreseeable physical, psychological, social, 
interpersonal, and economic risks introduced by the research. Include the source of the information. Consider both the 
probability and magnitude of harm and its impact. Describe the foreseeable harms associated with the research 
(untoward effects of a medication) and those related to delay to individualized treatment. Include data from the 
literature, and local data, if available, on risk rates and subject experiences with research procedures. Describe 
procedures in place to minimize risk. In general, please create a numbered list of risks/categories of risk, and in general 
put the list in the order of significance or level of risk, the most significant risks first followed by others. 
 
Cannabis: Possible side effects of smoked cannabis include: sedation, gait disturbance, tiredness, sadness, anxiety, 
concentration difficulties, increased heart rate, palpitations, dizziness, sleep disturbance, changes in food intake, 
restlessness, confusion, sleepiness, clumsiness, gastrointestinal upset, headache, nausea, dry mouth, pallor, flushing, 
sweating, and slurred speech. Side effects associated with cannabis withdrawal, e.g., sleep difficulty, irritability, upset 

Uploaded Protocol Summary Form 
 
 
 
stomach, restlessness, anxiety and loss of appetite may also occur. All participants are fully informed of the side effects 
that they might experience, and because all currently smoke cannabis, these effects should be familiar to them. 
 
Lorcaserin: Lorcaserin is well tolerated, with no evidence of the side effects commonly associated with 5HT2b or 5HT2a 
receptor agonists, e.g., abuse, hallucinations, cardiac valve disease (see Smith et al., 2010; Fidler et al., 2011; Shram et 
al., 2011). Transient and mild side effects include headache, dizziness, fatigue, nausea, dry mouth, constipation, cough, 
and back pain (Product label; Smith et al., 2010). Participants will be warned of rare but serious side effects include 
agitation, confusion, hallucinations, irregular heartbeat, depression, thoughts of suicide, and for men, an erection lasting 
longer than 4 hours. They will also be warned that they should use caution if they drink alcohol, drive a motor vehicle or 
operate heavy machinery until they know how the medication affects them (although they will be inpatient for all but 2 
of the 14 days they take the medication). Participants will not be taking any medications, but will be warned not to take 
any dietary supplements such as St. John's Wort, tryptophan and drugs that impair metabolism of serotonin, such as 
dextromethorphan since serotonin syndrome, a potentially life-threatening drug reaction, can occur when two drugs 
that affect the body’s level of serotonin are taken together. They will also be warned about the potential for heart valve 
problems and changes in white and red blood cells. 
 
Given that only healthy participants will be enrolled and will only receive an active dose of lorcaserin for 14 days, these 
rare side effects are even less likely. In clinical trials of 1-year duration: 2.4% of patients receiving lorcaserin and 2.0% of 
patients receiving placebo developed echocardiographic criteria for valvular regurgitation at one year. Decreases in 
white blood cell count were reported in 0.4% of patients treated with lorcaserin as compared to 0.2% of patients treated 
with placebo. Decreases in red blood cell count were reported by 1.3% of patients treated with lorcaserin as compared 
to 1.2% treated with placebo. The participants will be inpatient in a closely-monitored residential laboratory setting 
within the NY State Psychiatric Institute for 12 of the 14 days they are taking lorcaserin so we will monitor them closely 
throughout their participation. We will do an ECG at screening and at the end of the study, and assess vital signs each 
day. 
 
Inpatient Research Designs: There are also minor risks of isolation, boredom, and inactivity associated with living in the 
residential laboratory. In participants we have tested to date under similar conditions, such problems have been 
minimal. We describe at length possible difficulties of living in the residential lab before volunteers sign the study 
consent form. 
 
Phlebotomy: Participants will provide a blood sample during screening; they will be warned that blood drawing may 
cause slight discomfort at the site of needle entry and may result in a small bruise. 
 
Methods to Protect Confidentiality 
 
Describe the data management plan and the methods you will employ to protect subject privacy and the confidentiality 
of research data. The section should detail how information will be collected, recorded, coded, stored, transmitted, and 
as applicable, shared with other investigators so as to minimize risks related to breach of confidentiality. Confirm that 
identifiers are removed, to the extent possible, from research data, and explain if there are links between subject identity 
and research data, or if the data is anonymous. Also, indicate where the data is stored, who is responsible for its 
safekeeping, and who has access to subject identity and codes, if any, which cross-link research data and subject identity. 
Confirm that identifiable data is not collected, stored, or transmitted by mail, fax, on removable drives, laptops, or via the 
internet without proper protections, e.g. encryption. 
 
A Certificate of Confidentiality has been obtained for this study from the National Institute on Drug Abuse. Our records 
will be kept confidential and will only be accessible to study staff. Screening information, which may have the 
participant’s name, will be kept in a locked filing cabinet. Once a participant is enrolled into the study all further 
documents will be identified solely by initials and an assigned number. 

Uploaded Protocol Summary Form 
 
 
 
Describe only benefits to individual subjects that are likely to accrue during the study itself. Do not include subject 
compensation or treatment to be provided at the end of the study, as these do not figure into the IRB's risk benefit 
considerations. Do not describe diagnostic and evaluation components unless subjects receive clinical feedback. Do not 
describe the anticipated scientific benefits of the research. Some studies offer no direct benefit to subjects. 
There are few direct benefits to research volunteers in the proposed study. Prior to study acceptance, all volunteers will 
have a medical and psychiatric work-up. Thus, even if participants are not accepted into the study, they will benefit from 
these evaluations. We offer all participants the option of obtaining help to abstain from drug taking. Volunteers 
understand that they can obtain a referral for drug treatment at any stage of their research participation. We repeat our 
offer for treatment referral at discharge from the study. We will attempt to obtain a placement in a drug abuse clinic for 
those people who indicate a desire for help, and will inform all volunteers of our ongoing cannabis-treatment studies 
conducted within the Division of Substance Abuse. The major benefit of this research from our point of view is scientific. 
There is clearly a need for better treatment options for cannabis dependence. The model we are proposing to develop 
will allow us to better understand the effect of a potential treatment medication.. 
Direct Benefits to Subjects 

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References 

Uploaded Protocol Summary Form 
 
 
 
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