Clinical trial NCT04396834
Conditions: Tobacco Use Disorder Smoking Cessation
Sponsor: The Mind Research Network
Start date: 2019-12-04; Completion date: 2020-02-26
Enrollment: 3 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Identifying new medication options is critical for curbing the health burdens of cigarette smoking. Currently approved smoking cessation medications act on nicotinic receptors, and additional work is needed to identify medications with alternate pharmacological targets. Based on evidence that the serotonin system plays a role in nicotine consumption and relapse, this study will examine whether a selective serotonin medication alters smoking-related behaviors and responses to cigarette smoking under controlled conditions, informing its potential utility for smoking cessation.

Detailed description:
Tobacco use remains the foremost cause of preventable deaths in the U.S. and worldwide. Advancing new smoking cessation therapies, including those with novel pharmacological targets, is a critical public health priority. The serotonin (5-hydroxtytryptamine; 5-HT) system is broadly implicated in the regulation of reward- related behavior, including drug seeking, in part reflecting its modulatory role in dopamine (DA) function. Recent studies show that targeted manipulation of the serotonin 5-HT2C receptor alters drug-related behavior; in particular, 5-HT2C receptor agonists are shown to reduce nicotine intake and reinstatement. Of the selective 5-HT2C receptor agonists, lorcaserin has the best near-term potential for repurposing as a smoking cessation therapy, having been approved by the U.S. Food and Drug Administration for weight management.

Preclinical findings implicate several potential behavioral mechanisms by which 5-HT2C receptor agonists might reduce drug intake, including drug-specific processes (e.g., incentive salience of drug cues, self-administration, reinstatement) and drug-nonspecific behaviors (e.g., reductions in impulsivity). To date, potential mechanisms of 5-HT2C receptor agonists have not been characterized in human studies. Given emerging interest in lorcaserin as a novel smoking cessation therapy, further studies are needed to evaluate its efficacy profile, including studies to evaluate candidate treatment mechanisms. This human laboratory investigation will examine the effects of lorcaserin vs. placebo on relapse-related outcomes using a double-blind, within-subjects, crossover design. Impulsivity subdomains will also be examined as candidate mechanisms for medication effects. By evaluating an approved 5-HT2C agonist with emergent efficacy for smoking cessation, this project has near-term potential to inform clinical applications of 5-HT2C agonists for addiction.

Arms: arm 1: Participants first receive lorcaserin (10 mg BID) for 7 days. After a washout period of 7 days, they then receive placebo tablets (BID) for 7 days. arm 2: Participants first receive placebo (BID) for 7 days. After a washout period of 7 days, they then receive lorcaserin (10 mg BID) for 7 days.
Interventions: intervention 1: Lorcaserin Oral Tablet intervention 2: Placebo oral tablet
Intervention descriptions: intervention 1: Lorcasering 10mg Oral Tablet (BID) intervention 2: Placebo Oral Tablet (BID)

Protocol documents:
Prot_SAP_000.pdf: 
 
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UNM IRB PROTOCOL 
 
TITLE: 
Lorcaserin effects on smoking behaviors 
 
VERSION DATE: 
September 10, 2019 
PRINCIPAL 
INVESTIGATOR/ 
RESPONSIBLE 
FACULTY: 
Eric Claus, Ph.D., & Christian Hendershot, Ph.D., 
The Mind Research Network 
STUDENT 
INVESTIGATOR: 
n/a 
FUNDING AGENCY: 
National Institute on Drug Abuse 
 
BACKGROUND/SCIENTIFIC RATIONALE 
Despite declines in smoking prevalence in the United States, the likelihood of successfully quitting 
smoking has not improved [1, 2]. Roughly three in four smokers report the desire to quit, and up to half 
report past-year quit attempts [3, 4]. However, only 4-5% of smokers achieve sustained cessation in a 
given year [4], with relapse typically occurring within 5-10 days of a quit attempt [5, 6]. While the 
introduction of varenicline in 2006 was followed by marginally greater rates of pharmacotherapy 
utilization, no appreciable changes in sustained cessation have been observed since [4]. Given only three 
FDA-approved smoking cessation aids (varenicline, bupropion, and nicotine replacement therapy), 
advancing novel smoking cessation therapies is a critical aim [1, 7]. In principle, establishing a 
repertoire of medications will improve options for combination and personalized treatments [8-10].  
Because the three FDA-approved smoking cessation medications each act on nicotinic receptors, 
identifying novel therapies with alternate pharmacological targets is a key priority [1,7].  
 
The serotonin (5-HT) system is broadly implicated in the regulation of reward-related behavior, 
including drug seeking [11, 12], in part reflecting the role of 5-HT in regulating dopamine (DA) function 
[12, 13]. Historically, efforts to study the 5-HT system in relation to addiction have been complicated by 
the diversity of 5-HT receptors (7 distinct families and 14 receptor subtypes), as well as the opposing 
effects of some receptor subtypes on reward-related behavior [14]. Notably, selective serotonin reuptake 
inhibitors (SSRIs) have not proven efficacious for substance use disorders (SUDs) [11, 15]. However, 
given the diffuse action of SSRIs, and divergent effects of some 5-HT receptor subtypes on behavior, the 
evidence base on SSRIs does not rule out consideration of specific 5-HT receptors as therapeutic targets 
[11]. Importantly, the more recent development of highly selective 5-HT receptor ligands has allowed 
for targeted investigations of 5-HT receptor subtypes in preclinical models of addiction [11]. Of 
relevance to this application, substantial preclinical evidence supports the role of the 5-HT2C receptor in 
reward-related behaviors, including drug-seeking [11, 12, 16]. 
  
Considerable evidence shows that targeted modulation of 5-HT2C receptors alters reward-related 
behaviors, including food- and drug-related motivation, intake, and reinstatement [11, 17-19]. Generally, 
food- and drug-seeking behaviors are attenuated by 5-HT2C agonists, and may be enhanced by 5-HT2C 
antagonists [11, 14, 17]. The majority of work in preclinical models of addiction has concerned nicotine 
and cocaine. Notably, findings from several groups show that selective 5- HT2C receptor agonists 
(including Ro 60-1075 and lorcaserin) reduce both nicotine self-administration and reinstatement [11, 
16, 18, 20]. Fletcher and colleagues conducted much of the preclinical work on nicotine, demonstrating 
that 5-HT2C receptor agonists attenuate nicotine self-administration and reinstatement, as well as 
hyperactivity and impulsive responding induced by nicotine [11, 18, 20, 21]. Notably, both acute 


 
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(single-dose) and chronic lorcaserin treatment reduces nicotine self-administration in non-human 
primates [22]. Moreover, treatment with 5-HT2C receptor agonists attenuates self-administration of 
cocaine and other addictive drugs, raising the prospect of broader therapeutic applications for SUD [11, 
16]. Clinical applications of 5-HT2C receptor agonists. Reflecting the role of 5-HT2C receptors in 
consumptive behaviors, selective 5-HT2C drugs were developed largely in pursuit of novel treatments 
for obesity. In 2012, lorcaserin (Belviq®) became the first FDA-approved selective 5-HT2C receptor 
medication for weight management. Approval of lorcaserin was based on three large Phase III trials 
totaling nearly 7800 subjects [23- 25]. In these studies, lorcaserin led to significant weight reduction 
with a favorable safety profile. Importantly, while the off-target side effects of non-selective 5-HT 
agents (e.g., fenfluramine) have prevented clinical translation, extensive Phase II/III work shows that 
lorcaserin has a favorable safety profile [26, 27]. Following from preclinical work with nicotine, an 
initial Phase II study of lorcaserin with smokers was reported recently [28]. Smokers were randomized 
to placebo or lorcaserin at one of two doses: 10mg QD (daily) or 10mg BID (twice daily). Relative to 
placebo, 10mg BID (the FDA-approved dose) significantly increased continuous abstinence rates (OR = 
3.02, 95% CI = 1.47-6.22) [28]. Lorcaserin also had a favorable safety profile in smokers, with the most 
common side effects including headache, fatigue and nausea. As the only 5-HT2C medication with 
Phase III validation and FDA approval, lorcaserin has near-term potential for repurposing as a candidate 
SUD treatment [11, 16]. Further human work is needed to clarify lorcaserin’s effects on smoking-related 
behaviors. 
 
Clarifying mechanisms of treatment efficacy is critical for informing intervention design. Importantly, 
evidence that 5-HT2C receptor agonists reduce both food- and drug-seeking implies the possibility of 
one or more common mechanisms. Although the efficacy of 5- HT2C agonists for weight reduction was 
initially attributed to their effects on satiety, evidence that 5-HT2C agonists reduce operant responding 
for conditioned reinforcers strongly implicates motivational, appetitive and/or hedonic processes [17]. 
As reviewed recently by Fletcher and colleagues [17], a leading possibility is that 5-HT2C receptor 
agonists reduce responding for conditioned reinforcers by altering DA-mediated incentive motivation, 
consistent with the role of 5-HT2C receptors in 5-HT-related inhibition of DA function. Specifically, 5- 
HT2C agonists are shown to blunt DA release in the nucleus accumbens (NAc) under basal conditions 
[13, 29, 30]and, furthermore, to blunt drug-induced NAc DA release [31]. These data imply that 5-
HT2C agonists could reduce drug-seeking by way of a generalized inhibitory effect on DA function, 
and/or by inhibiting DA activity associated with conditioned drug cues specifically. Consistent with the 
latter possibility, the first human imaging study of lorcaserin showed reduced BOLD response to 
hedonic food cues after one week of treatment [32].  
 
Another explanation for 5-HT2C agonists' ability to reduce food and drug intake concerns their 
influence on impulsivity. Behavioral indices of impulsivity are generally attenuated by 5-HT2C agonists 
(and amplified by 5- HT2C antagonists), typically in the absence of altered baseline motor activity [17]. 
These findings have informed the hypothesis that the ability of 5-HT2C receptor agonists to reduce 
food/drug intake are partly mediated by reductions in impulsive responding (or conversely, improved 
inhibitory control) [17]. Given the central role of impulsivity in drug intake and relapse liability [33, 34], 
support for this hypothesis in human studies could carry significant implications: therapies that 
concurrently reduce drug intake while improving behavioral control would have particularly high appeal 
[35]. Of note, preclinical evidence indicates that 5-HT2C receptor agonists may have differential effects 
on measures of impulsive action (e.g., premature responding) versus impulsive choice (e.g., temporal 
discounting) [17]. While speculative at present, these findings could imply that specific impulsivity 
domains are involved in mediating drug effects on reward-related behavior. To date, no human studies 
have sought to characterize the effects of 5-HT2C agonists on impulsivity domains. 
 
Human laboratory studies play a pivotal role in drug development by providing an efficient, cost-
effective bridge between preclinical studies and full-scale randomized trials [36-43]. By allowing 


 
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efficient cross-validation of both preclinical and Phase III results, human experimental studies serve a 
cornerstone role in translational drug development [7, 36, 37, 44]. An ancillary advantage of these 
studies is the ability to test putative mechanisms of pharmacotherapy effects under controlled 
experimental conditions [41]. As noted, clarifying treatment mechanisms is a critical goal that ultimately 
informs treatment design, and can also inform selection of clinical endpoints for Phase III trials [36]. 
Notably, most candidate SUD medications are tested in Phase III trials without prior or subsequent study 
in human laboratory models [36]. Despite lorcaserin’s appeal as a candidate therapy for smoking 
cessation [11, 16], no human laboratory investigations of lorcaserin have been reported. Importantly, 
recent reviews have also highlighted areas in which laboratory studies can be improved. First, many 
laboratory studies are limited by a sole focus on self-report outcomes (e.g., craving), which lack a direct 
analogue in animal models [45, 46]. Relative to self-report outcomes, drug self-administration outcomes 
appear more sensitive to pharmacotherapy effects, and may improve consistency in findings across 
preclinical and human studies [36]. Additionally, self-reported craving - while undoubtedly a clinically 
important construct - is neither necessary nor sufficient for self-administration, supporting the need to 
prioritize objective self-administration outcomes [47]. Another limitation of most human lab studies 
concerns their discordance with Phase III trials in terms of sample characteristics. A key limitation, as 
highlighted in a recent systematic review, is that human laboratory studies of smoking pharmacotherapy 
typically recruit non-motivated smokers, limiting comparisons with Phase III trials [44]. Importantly, 
evidence shows that recruiting non-motivated smokers undermines the ability to detect medication 
effects, whereas recruiting smokers with some motivation to quit (even if not engaged in an active quit 
attempt) improves effect sizes in medication screening trials [39]. 
 
OBJECTIVES/AIMS 
The proposed project will leverage human laboratory methods to study behavioral processes by which 5-
HT2C receptor agonism might alter cigarette consumption and relapse. Using a double-blind, within-
subjects, counterbalanced laboratory design, we will randomize smokers to short-term treatment with 
lorcaserin (10mg twice-daily) or placebo prior to completing human laboratory sessions. Laboratory 
endpoints will include both nicotine-specific (e.g., reinstatement, self-administration) and nicotine-
nonspecific (e.g., impulsivity) outcomes selected on the basis of preclinical studies of 5-HT2C receptor 
medications. 
 
Aim 1. To examine the effects of lorcaserin vs. placebo on laboratory indices of nicotine reinstatement 
(lapse) and self-administration. 
 
Aim 2. To examine the effects of lorcaserin vs. placebo on nicotine-nonspecific behavioral processes 
implicated in preclinical studies of 5-HT2C receptor drugs. 
PROJECT DESIGN 
I. 
Target Population and Inclusion/Exclusion Criteria 
A final sample of 42 nicotine-dependent cigarette smokers will be recruited from the community.    
Inclusion Criteria 
a) age 18-65 [28] 
b) smoking 5+ cigarettes per day (average) over the past year, with no period of abstinence > 90 
days  
c) biochemical verification of smoking status, based on expired CO > 8 at baseline 
d) baseline Fagerström (FTND) score of 5+ (indicating at least moderate nicotine dependence) 


 
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e) reporting long-term motivation to quit smoking (defined as interest in a quit attempt within the 
next 12 months [39]) 
f) willingness to take study pills and complete study procedures 
g) willingness to complete lab sessions involving cigarette smoking 
 
Exclusion Criteria 
a) meeting DSM-5 criteria for substance use disorder aside from tobacco use disorder and mild 
cannabis use disorder 
b) recent (30 day) illicit drug use (except marijuana), based on self-report and urine drug screen 
c) Past 30-day use of tobacco cessation aids or nicotine/tobacco products other than cigarettes 
d) Past 30-day use of SSRIs, other psychiatric medications, or weight control medications 
e) lifetime diagnosis of severe mental illness (e.g., psychotic or bipolar I disorder) 
f) significant medical or neurological illness based on the medical staff (i.e., physician or nurse 
practitioner) evaluation including severe hepatic impairment or cirrhosis, insulin dependent diabetes  
g) actively engaged in smoking cessation treatments or a smoking cessation attempt (or intent to start 
an attempt in the next 90 days) 
h) interested in quitting smoking immediately (i.e., in the next two months) 
i) Medications which are contraindicated for use with lorcaserin (bromocriptine, cabergoline, 
dapoxetine, dihydroergotamine, ergoloid mesylates, ergonovine, ergotamine, methylene blue, 
methylergonovine, nicergoline, pergolide, thiorizadine) or which have a significant interaction with 
lorcaserin (bupropion, doxorubicin, eliglustat, linezolid, perhexiline, rasagiline, safinamide, 
selegiline, tamoxifen)  
j) body mass index (BMI) under normal range (BMI < 18 kg/m2) 
k) history of significant cardiovascular conditions including history of arrhythmias or heart block, 
heart failure, valvular heart disease, heart attack, stroke, unstable angina 
l) abnormal electrocardiogram (ECG) results 
m) nursing, pregnant, or anticipating pregnancy 
n) history of suicide attempt or recent suicidal ideation (i.e., Suicidal thoughts (intent or plan) in the 
last month) 
o) Plans to travel outside of the Albuquerque area during the study period, or inability to commit to 
entire duration of study (6 weeks of potential availability) 
 
 
II. 
Participant Enrollment 
We anticipate phone screening up to 1000 individuals and may consent up to 100 participants 
in order to obtain a final sample of 42 eligible participants who complete all study sessions. 
 
III. 
Recruitment and Screening Procedures 
Participants will be recruited from the community. Participants will be recruited through 
flyers, radio/TV ads, movie theaters, word of mouth, press releases, newspaper ads, business 
cards, online postings (e.g. Craigslist, Google Adwords, Facebook, Instagram, 
clinicaltrials.gov) within the Albuquerque metro area, and email communications directed 
towards community groups. Approved study recruitment text and flyers will be used in 
digital recruitment mediums, such as university list-servs, online advertising mediums, or 
digital presentation slides. Word of mouth from current and past participants, employees and 
collaborators, as well as other individuals will also be used and may include sharing 
approved information and/or recruitment materials. Finally, participants from other studies 
who have expressed an interest in being contacted for future studies, including from the 


 
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MRN Participant Recruitment Registry, may be contacted to determine eligibility and interest 
in this study. 
Potential subjects other than those from the MRN Participant Recruitment Registry, will be 
self-selected and must contact the study to express initial interest in the study. Once initial 
contact is made, research staff will explain the study and conduct a brief phone screen 
interview.  
Recruitment materials are included with the application (attachments are listed below).  
IV. Informed Consent Process 
Upon initial contact, the study will be briefly introduced to the participant by a member of the 
research team. Participants will then complete a preliminary screen over the phone. Identifiable 
information will be retained for those participants who do not meet inclusion criteria only for the 
duration of the study to ensure that the same participant does not attempt to enroll a second time. If 
the participant meets inclusion criteria, the study visit will be scheduled and a copy of the consent 
document will be sent to them in advance if requested. Participants requesting the consent ahead of 
their visit will be allowed as much time as they need to decide whether or not to participate, and the 
PI or study staff will be available to answer questions about the consent/study procedures while the 
participant is making their decision. When the participant arrives for their appointment, they will be 
seated in a private room and given time to read the consent form with a study team member present. 
After the participant has finished reading the consent form, the study is described more fully by the 
research team and the participant is asked whether they have any questions regarding the described 
procedures and risks/benefits. Participants must elect to participate and can choose to discontinue 
their participation in the study at any time. No coercion or undue influence will be used.  
Additionally, participants can be withdrawn from the study by the PIs for any reason (e.g., not 
paying attention to tasks, failure to attend scheduled appointments, not following directions, safety 
concerns)  throughout the course of the study 
If there are no further questions, the consent form is signed and stored in a locked cabinet in a locked 
office at MRN. A copy of the consent will be given to the participant. 
 
V. 
Data Collection Procedures 
 
In total, participation in this study will take roughly 18 hours over a period of approximately 5 
weeks. This includes a screening visit (up to 3 hours), a baseline visit (up to 3 hours), and two 
follow-up visits (up to 5 hours each).  In addition, participants will complete a follow-up medication 
refill visit (1 hr.) and daily questionnaires online (using Redcap) every day (1-2 minutes per day), 
and will receive calls twice from staff during each of the medication phases to check in on side 
effects (up to 15 minutes per call). 
Participants will be asked to complete the following procedures: 
Telephone screen 
Initial participant screening will be conducted by telephone by trained research staff and will assess 
participant cigarette, alcohol, and drug use, medications, and medical history. Potential participants 
will be given a brief description of the study, following a designated script. Contact information will 
be collected from interested callers who pass the initial screen who will then be scheduled for in-
person screening, consent, and medical assessment. The initial telephone contact is estimated to take 
roughly 10-15 minutes. Included in the phone screen will be a series of questions about interest in 
quitting (e.g. are you interested in making an attempt to quit in the next 3, 6, or 12 months?). This 
question is to ensure that a) participants are not planning to make an imminent quit attempt in the 
next 3 months (given the laboratory smoking sessions), and b) that participants report some degree 


 
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of long-term motivation to quit (which has been shown to increase effect sizes in medication 
screening studies). 
 
Screening and Baseline Data Collection Visits 
Prior to any assessments, we will obtain informed consent from all participants.  The in-person 
screening visit will include both a clinically-oriented screen by a medical staff member (study 
physician or nurse), and self-report and interview questions, conducted by the research assistant 
or medical staff member. The staff will administer a urine drug screen (for females, the test will 
also include a pregnancy screen), and then briefly review and verify information collected over 
the phone.  In all cases in which the pregnancy test shows a positive result, the results of the test 
will be given to only the participant in a private room. We will also measure expired alveolar 
carbon monoxide (CO) at the screening visit. 
 
Additional screening criteria, including symptoms of nicotine and alcohol dependence, and 
aspects of medical history (see criteria listed above) will be assessed. The Structured Clinical 
Interview for DSM-V [76] will be used to assess inclusionary and exclusionary diagnoses. The 
Timeline Follow-Back (TLFB) [77] will be used to assess cigarette, alcohol, and other drug use 
in the 90 days prior to baseline, and the Fagerström Test of Nicotine Dependence [78] will be 
used to assess nicotine dependence. Consistent with prior studies [39], motivation for cessation 
at screening will be measured by asking participants about intent to quit in the next 3, 6, and 12 
months (intent to quit within 12 months serves as the index of motivation, whereas intent to quit 
within 3 months will be exclusionary). The urine sample will be used to test for the presence of 
several drugs (for example, marijuana, heroin, cocaine, methamphetamines, opiates). If a 
participant tests positive for drugs other than marijuana (or if females screen positive for 
pregnancy) the participant will be excluded from the study. Additionally, participants will 
complete a blood draw (up to 20 ml) for a complete blood count (CBC), a basic metabolic panel, 
and a hepatic function panel. The baseline blood sample will also serve as the sample for DNA 
analysis. Blood draws will be performed by trained research staff.  Participants will also 
complete an ECG test. ECG results will be evaluated by qualified medical staff. During the 
medical history any medications that the participant is taking will be checked for interactions 
with lorcaserin in an established online database such as Epocrates or Lexicomp, and prescribing 
medical staff will be contacted for dose adjustments, if deemed necessary. The initial consent 
and eligibility interview session is projected to take up to 3 hours. 
 
If results of the baseline screening/medical assessment indicate that the participant is eligible, they 
will be scheduled for a return baseline visit. This visit will include a more comprehensive orientation 
to the study, a questionnaire battery, cognitive tasks, and dispensing of the first set of study pills.  
Any incidental medical findings during the assessment or subsequent participation in the study will 
be communicated by the MD or NP directly to the participant. 
 
Participants who meet all study eligibility procedures will be provided with a study overview, and 
locator and collateral contact information will be obtained.  
A Demographic Screening Questionnaire will assess basic demographic factors (e.g., age, 
education, income). The Timeline Follow-Back (TLFB) [77] will be used to assess cigarette, 
alcohol, and other drug use since the screening visit, and during the study phase. Other baseline 
measures will include the Nicotine Dependence Syndrome Scale [79], the Wisconsin Inventory of 
Smoking Dependence Motives [80], and the Alcohol Use Disorders Identification Test [81]. To 
assess stages of motivation during the study, and a Contemplation Ladder [82]. The PROMIS 
Depression scale and Beck Depression Inventory-II will be administered to assess potential 
negative effects on depressive symptoms.  If participants report suicidal ideation, standard MRN 
protocols will be followed, including further assessment of the participant by medical staff and/or 


 
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the PI, offering a referral, and following up with the participant.  The Wechsler Test of Adult 
Reading will be administered to obtain an estimate of IQ.  The Yale Craving Scale will be used 
to measure craving/withdrawal over the past week.  When possible, baseline questionnaires will be 
collected using a computerized system (i.e., Redcap). Any measures that would be expected to show 
change across sessions (or in response to medication) will be repeated at follow-up visits. 
Participants will also be asked to provide a saliva sample for genetic analyses. The primary objective 
of these analyses is to examine functional variants in the CYP2A6 gene. The CYP2A6 enzyme is 
primarily responsible for the metabolism of nicotine. Several CYP2A6 variants have been identified 
that alter nicotine metabolism, and some have been linked to smoking outcomes. Because CYP2A6 
variation has also been linked to responses to nicotine pharmacotherapy, we will examine genetic 
moderators of response to medication effects on smoking outcomes. We may also investigate genetic 
variants implicated in substance use and related traits (e.g., impulsivity, which is another focus of the 
present application). 
Impulsivity/Learning Tasks: To examine medication effects on behavioral measures of impulsivity 
and reward-based learning (as reported in preclinical studies), participants will complete 
computerized cognitive tests of impulsive action, attention, and reward-based learning at the baseline 
session, lasting roughly 45 minutes in total duration. These measures will be repeated at follow-up 
visits. These tasks include: Stop Signal, Continuous Performance Test, Monetary Choice 
Questionnaire, Cigarette Discounting Task, Food Discounting Task, Cigarette Purchase Task, and a 
Reward Responsiveness Test. 
The baseline session will require up to 3 hours to complete.  Patients will be given breaks, snacks, 
and bottled water as needed.  
 
Medication Schedule and Safety Monitoring. Participants will receive the first 7-day supply of 
pills (medication or placebo, randomized and counterbalanced) at the completion of the baseline 
visit. In the first Phase II trial of lorcaserin for smoking cessation, the FDA-approved dose of 10mg 
BID (twice-daily) significantly increased abstinence relative to placebo, with a larger effect size 
relative to a comparison low-dose condition (10mg QD / once-daily) [51]. The BID and QD 
conditions were equivalent on discontinuations due to adverse events (AE; 2.5% and 3.0%, 
respectively) [51]. Therefore, we will use the FDA-approved dose of 10mg BID. Of note, steady-
state plasma concentration occurs in 3 days. All pills will include a small amount of riboflavin to 
facilitate urinalysis as an index of adherence, and participants will be asked to bring their pill bottles 
at each visit. To monitor emergent side effects, the study staff will contact participants twice during 
the 7 day period (e.g., days 2 and 4). On Day 7 participants will return to complete the human 
laboratory session described below. This visit will also include a repeat of the medical 
tests/measurements (noted above), a calendar-based assessment of interim cigarette use, other 
substance use, and medication adherence, and a pill count. Following the laboratory visit on Day 7, 
participants will undergo a washout phase of at least 7 days. Next, they will repeat the same 7-day 
sequence in the alternate pill condition, culminating in a second, identical human laboratory session. 
Depending on scheduling and participant availability, we will be flexible in accommodating slight 
deviations from the 7-day schedules noted above, and at the discretion of the physician, participants 
may be provided with additional days of medication as needed. During the medication phases, side 
effects will be assessed with the SAFTEE questionnaire [106] and an Adverse Events Checklist 
[107].  Participants will complete a brief web-based assessment each morning using Redcap (link 
texted by research staff or automated system), including 1) prior-day number of cigarettes smoked; 
2) peak prior-day craving; 3) any emergent side effects; and 4) medication adherence for the prior 
day. Participants will have the option of completing the brief survey via smart phone. If participants 
do not own a smart phone, we will provide an email link to the survey, or if preferable, a text 
message containing the survey questions. 


 
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Follow-up Sessions 1 and 2. At each of two identical sessions (corresponding with the end of the 
medication weeks), participants will report to MRN in the morning, after receiving instructions to 
abstain from cigarettes (overnight) and from and alcohol (for 24 hours). Expired alveolar carbon 
monoxide (CO), breath alcohol concentration (BrAC), body weight, and heart rate/blood pressure 
will be collected at each in-person visit. Upon arrival, overnight smoking abstinence will be verified 
based on expired CO of <6ppm (or <50% of the initial screening reading). Participants will then 
provide a urine sample for riboflavin detection (as an index of adherence). A blood sample (up to 20 
ml) will then be taken in order to assess metabolite levels of the medication.  Blood draws will be 
performed by trained research staff.  Participants will take that day’s medication dose under 
supervision.  Sessions will include three main elements: 1) computerized measures of impulsivity 
and reward sensitivity, 2) follow-up self-report (e.g., cigarette use, craving, self-efficacy) and 
medical (e.g., side effects, body weight) assessments, and 3) laboratory measures of smoking cue 
reactivity, reinstatement, and self-administration, as detailed below. The latter tasks will occur in a 
place equipped with a ventilated system for smoking studies. 
Computerized behavioral tasks. Participants will complete validated behavioral tasks assessing 
impulsive action and impulsive choice, as described below. Selection of these constructs is based on 
preclinical observations that 5-HT2C receptor agonists reduce impulsive responding, and may 
preferentially influence measures of impulsive action, as opposed to impulsive choice. Because 
another possible mechanism by which lorcaserin influences consumptive behaviors is through 
reduced sensitivity to reinforcers generally [17], we will also include a validated behavioral assay of 
reward responsiveness. Tasks will be administered twice at the follow up visit (prior to and 
following the lapse procedure) to assess possible changes following nicotine exposure. These tasks 
include: Stop Signal, CPT, Monetary Choice Questionnaire, Cigarette Discounting Task, Food 
Discounting Task, Cigarette Purchase Task, and a Reward Responsiveness Test. 
Cue-elicited craving. Human studies of the effects of 5-HT2C agonists on cue-elicited drug craving 
have not been reported. To address this objective, we will utilize an established cue reactivity task to 
assess peak provoked craving (PPC). This procedure, which involves assessing craving during a cue 
exposure task (lighting a cigarette and attending to cues) while in a period of short-term abstinence, 
has been demonstrated to reliably induce acute craving [71]. Given the potential for differential 
medication effects on tonic vs. phasic craving [74], tonic craving will also be assessed as a 
component of the repeated self-report assessments (noted below). 
 
Simulated lapse. The cue reactivity task will lead directly into the simulated lapse procedure 
developed by McKee, who is a consultant on this project [38, 75]. Importantly, preclinical evidence 
shows that lorcaserin reduces both nicotine reinstatement and self-administration. The McKee 
paradigm is the only validated laboratory procedure that models each of these outcomes [38]. In this 
procedure, a nicotine deprivation period (e.g., overnight abstinence) provides a context to study 
medication effects on reinstatement [38]. Participants will be presented with a package of their 
preferred cigarettes (participants will be asked to bring one unopened pack in to the session). 
Participants will given the choice to initiate cigarette smoking, or to delay smoking for up to 50 
minutes in exchange for monetary reinforcement. Prior studies show that a reinforcement schedule 
of $1 for every 5 minutes results in participants resisting, on average, for 25 minutes, providing ideal 
variability in time to reinstatement [38]. If no lapse occurs (i.e., the participant resists for 50 
minutes), participants will not be forced to smoke a cigarette. Following the initial decision to 
smoke, participants will complete assessments of craving, withdrawal, and subjective effects 
(described below). 
 


 
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Next, a 60-minute period of ad libitum smoking will ensue [68]. Participants will be presented with a 
tray containing 8 cigarettes from the package, and will have the opportunity to smoke additional 
cigarettes at their discretion [68]. Again, participants will not be forced to smoke a cigarette. 
Repeated ratings of craving, withdrawal, and subjective effects will be taken at 15-minute intervals 
during the self-administration period. A follow-up measure of expired CO will be taken at the end of 
the session to measure CO “boost”, an additional index of cigarette intake. 
 
The primary outcomes for the human laboratory sessions consist of 1) nicotine reinstatement (i.e., 
minutes of resistance to smoking reinstatement), and 2) nicotine self-administration (i.e., cigarettes 
consumed during ad libitum smoking). These primary outcomes are selected because they reflect 
objectively defined behaviors analogous to those reported in preclinical studies of 5-HT2C 
medications. Secondary human laboratory outcomes will include peak-provoked craving during the 
cue exposure task, CO boost, and subjective effects during nicotine self-administration, e.g., 
assessed by the Modified Cigarette Evaluation Scale [90] and the Drug Effects Questionnaire 
[91]. The Positive and Negative Affect Scale [92] will also assess change in mood.  
 
To assess lorcaserin's effects on behavioral measures of impulsivity, we will use validated measures 
of impulsive action (a Continuous Performance Test, CPT), and impulsive choice (the Monetary 
Choice Questionnaire, MCQ, assessing temporal discounting). The Connors’ CPT II task [93] 
requires participants to attend to a sequence of numbers and press a button for every letter that 
appears on the screen except the letter ‘X’. The task outcomes include number of correct detections, 
(a measure of attentional capacity), reaction time (processing speed), omission errors (distractibility), 
and commission errors (a measure of impulsivity and the key outcome for this study). Importantly, 
preclinical studies have found effects of 5-HT2C drugs on impulsivity when using the 5-choice 
Serial Reaction Time Task [94, 95], which was originally designed as a rodent analogue of the CPT. 
The MCQ [96]is a measure of temporal discounting (or impulsive choice). Participants indicate their 
preferences on each of 27 items that present an immediate and delayed reward (e.g. $19 today or $25 
in 53 days). From these choices, it is possible to derive a discounting value, k, reflecting the extent to 
which one discounts future rewards in favor of immediate rewards. A similar Cigarette Discounting 
Task [103], and a Cigarette Purchase Task [104] will further serve as behavioral indices of drug-
related impulsive choice. Finally, given the additional possibility that 5-HT2C agonists may reduce 
aspects of reward-based responding generally, a Reward Responsiveness Test [97] will be included. 
In this task, participants must discern between two similar, briefly presented (i.e. 100ms) stimuli. 
During each block of 100 trials, participants receive rewards on 40 of the correct trials; however, 
unbeknownst to participants, the two stimuli are rewarded on different reinforcement ratios, leading 
to systematic bias in responding. The key outcome is response bias (indexing bias towards reward-
based learning). 
 
Table 1. Study Measures  
VISIT 
MEASURE/PROCEDURE 
TIME 
(MINS) 
Screening 
 
Consent 
30 
Urine drug screen 
5 
Urine pregnancy test (females) 
5 
Blood draw 
5 
Expired CO 
2 
Intention to quit/treatment status 
2 
FTND 
1 
TLFB 
30 
SCID 
60 
 
The Wechsler Test of Adult Reading (WTAR) 
10 
Physical Exam 
10 


 
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UNM IRB Protocol Template v01.19.18 
VISIT 
MEASURE/PROCEDURE 
TIME 
(MINS) 
Medical screen (may occur 
on different day than 
screening depending on 
availability) 
Medical History 
15 
EKG 
20 
Baseline/First Dispensing 
Visit 
Demographics form 
5 
Locator form 
10 
AUDIT 
2 
TLFB (since last visit) 
10 
NDSS 
3 
WISDM 
10 
Yale Craving Scale 
5 
TQSU 
1 
UPPS-P 
5 
Contemplation Ladder 
1 
Three Factor Eating Questionnaire 
3 
Reward-Based Eating Drive Scale 
2 
Simplified Nutritional Appetite Questionnaire 
2 
PROMIS Depression/BDI-II 
4 
Cigarette Self-efficacy Questionnaire 
1 
Stop signal 
10 
CPT 
10 
Reward Responsiveness Test 
15 
Monetary Choice Questionnaire 
2 
Cigarette Discounting Task 
2 
Food Discounting Task 
4 
Cigarette Purchase Task 
2 
 
SAFTEE/Adverse Effects Checklist 
10 
Between Baseline & Follow 
up visit 1 
Call participant on days 2 and 4 to assess side effects 
 
            SAFTEE/Adverse Effects Checklist 
10 
Follow up visit 1 (including 
smoking session) 
Expired CO/Breath Alcohol 
4 
Weight 
2 
Blood draw 
5 
Take dose of medication  
2 
Pill count 
2 
PROMIS Depression/BDI-II 
4 
Cigarette Self-efficacy Questionnaire 
1 
Cigarette Purchase Task 
2 
Cigarette Discounting Task 
2 
Monetary Choice Questionnaire 
2 
Stop Signal task 
10 
CPT 
10 
Food discounting task 
4 
Yale Craving Scale 
5 
Reward Responsiveness Test 
15 
PANAS 
2 
Heart rate/blood pressure 
5 
Three Factor Eating Questionnaire 
3 
Reward-Based Eating Drive Scale 
2 
Simplified Nutritional Appetite Questionnaire 
2 
SAFTEE questionnaire 
8 
Adverse Effects Checklist 
5 
Cue elicited craving 
10 


 
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VI. Anticipated End Date 
 
We anticipate completing all data collection by March of 2021. At the time of study closure, 
after all follow-up data have been collected, all participant identifiers (name, address, etc.) will 
be made inaccessible to the research team. MRN retains the link between identifiers and URSI 
indefinitely for the potential future benefit to the research participant. Specifically, it may 
become medically advantageous in the future for a former participant to have access to the 
clinical information that may be present in the medical screening. 
  
VII. Project Location(s) 
All study procedures and participant interactions will take place at the Mind Research Network.  
 
VISIT 
MEASURE/PROCEDURE 
TIME 
(MINS) 
Simulated lapse paradigm 
120 
Drug Effects Questionnaire 
2 
Modified CEQ 
5 
Washout 
7 days with no medication 
 
Weight/Blood Pressure 
5 
TLFB (since last visit) 
5 
SAFTEE/Adverse Effects Checklist 
2 
Simplified Nutritional Appetite Questionnaire 
2 
Dispense 2nd medication 
10 
Follow up visit 2 (including 
smoking session) 
Expired CO/Breath Alcohol 
4 
Weight 
2 
Blood draw 
5 
Take dose of medication  
2 
Pill count 
2 
PROMIS Depression/BDI-II 
4 
Cigarette Self-efficacy Questionnaire 
1 
Cigarette Purchase Task 
2 
Cigarette Discounting Task 
2 
Monetary Choice Questionnaire 
2 
Stop Signal task 
10 
CPT 
10 
Food discounting task 
4 
Yale Craving Scale 
5 
Reward Responsiveness Test 
15 
PANAS 
2 
Heart rate/blood pressure 
5 
Three Factor Eating Questionnaire 
3 
Reward-Based Eating Drive Scale 
2 
Simplified Nutritional Appetite Questionnaire 
2 
SAFTEE questionnaire 
8 
Adverse Effects Checklist 
5 
Cue elicited craving 
10 
Simulated lapse paradigm 
120 
Drug Effects Questionnaire 
2 
Modified CEQ 
5 


 
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VIII. Participant Compensation 
 
To compensate participants for their time, participants will receive cash compensation. The 
payments will be allocated as follows: $50 for completing the eligibility and medical screening 
visit; $60 for completing the baseline visit; $100 completing the first experimental session; and 
$150 for completing the second experimental visit.  For each of the experimental sessions, 
participants will receive a $30 bonus for having a breath CO < 6 or less than half of the baseline CO 
reading, which are indicative of overnight abstinence. In addition, during the smoking lapse task at 
each follow-up session, it is possible for participants to earn up to an additional $10 for resisting 
smoking for the entire 50 minutes.  Participants will also receive a $30 bonus for completing at least 
75% of daily Redcap assessments, and a final bonus of $50 for completing all of the study visits (to 
be paid at the final visit). Therefore, the total possible compensation is $520. In the event 
participants are not able to pick the final cash payment in person, we will offer the option of issuing 
the final payment via electronic gift card to the participant’s email address. 
 
IX. Project Resources 
 
Five private, closed door rooms will be available to research staff for study visits at MRN. These 
assessment rooms have white noise generators outside of the doors to prevent conversations from 
being overheard. These are reserved by investigators as needed, and are easily accessible.  All 
MRN research staff are trained in regards to the HIPAA Privacy Rule. All individuals will be 
trained to administer the same consenting and study procedures. Further, all study personnel will 
have current CITI and HIPAA training throughout the period of the study. 
 
EXPECTED RISKS/BENEFITS 
I. 
Potential Risks  
Safety and Side Effects Profile of Lorcaserin. Lorcaserin (Belviq®) received FDA approval in 
2012 for the indication of weight reduction in patients with obesity (or patients with overweight 
status and at least one weight-related comorbid condition, such as diabetes). Lorcaserin received 
FDA approval based on the results of three large, Phase III randomized trials totaling nearly 7,800 
subjects. In these trials, lorcaserin was efficacious for weight reduction (e.g., 47.1% of lorcaserin-
treated patients had body weight reduction of 5% or more at 12 months, versus 22.6% of placebo-
treated participants). The extensive evaluation of lorcaserin in Phase III trials, including subsequent 
pooled analyses of the safety/side effect data from Phase III trials [114, 115] has generated 
considerable data on lorcaserin's safety profile. These trials jointly comprise the largest obesity 
pharmacotherapy dataset in the United States to date.  
In studies where lorcaserin was taken for a longer period of time (at least one year), the most 
commonly reported side effects (i.e., greater than 5% of participants and more common than 
placebo) included: 
 
• 
headache 
• 
dizziness 
• 
fatigue 
• 
nausea 
• 
dry mouth 
• 
constipation 
• 
nasopharyngitis (nasal/throat irritation, similar to a common cold) 
 


 
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Additionally, the less common side effects (reported by 2% or more of patients) included: 
 
• diarrhea 
• vomiting 
• upper respiratory tract infection 
• urinary tract infection  
• back pain 
• musculoskeletal pain 
• cough 
• oropharyngeal pain (e.g., sore throat) 
• sinus congestion 
• rash 
The most commonly reported side effect/adverse event (AE) in Phase III trials of lorcaserin was 
headache (16.8% of lorcaserin participants vs. 10.1% of placebo participants). The next most 
common AEs were upper respiratory tract infection (13.7% lorcaserin vs.12.3% placebo), 
nasopharyngitis (13.0% vs. 12.0%), dizziness (8.5% vs. 3.8%), and nausea (8.3% vs. 5.3%). Side 
effects were generally time-limited, with differences in side effects between experimental groups 
being observed primarily during the first 1-2 weeks of medication. Rates of serious adverse events 
(SAEs) were 2.7% and 2.3% in lorcaserin and placebo groups, with 0.3% and 0.2% of participants in 
these respective groups experiencing treatment-emergent SAEs. None of the reported SAEs occurred 
in more than one participant. Study discontinuations due to AEs were slightly more common in the 
medication than placebo groups, however, the placebo-adjusted discontinuation rate of medication-
emergent AEs was small (1.8%). Headache was the only single AE associated with a discontinuation 
rate of >1% (1.8% lorcaserin, 0.8% placebo). There was no evidence of treatment-emergent 
psychiatric side effects (e.g., increases in depression, suicidality) or symptoms of "serotonin 
syndrome." [114, 115]. Pooled analyses from the Phase III trials also showed that lorcaserin-treated 
participants had significantly improved outcomes on several secondary measures relative to the 
placebo group, including significantly greater improvements in lipid profiles and glycemic 
indicators. Notably, the medication group also reported greater improvements on a measure of 
quality of life [115]. Based on Phase I research with lorcaserin, the drug received a Schedule IV 
designation upon its FDA approval in 2012, due to potential perceptual or quasi-hallucinogenic 
effects of the drug. However, in a Phase III project examining lorcaserin as an obesity treatment 
involving roughly 3,400 participants, no reports of hallucinogenic effects emerged in lorcaserin-
treated participants, and only six participants reported mild-to-moderate euphoric effects while 
taking the drug [116]. Further, subsequent experimental research has suggested no effects on 
perceptual outcomes, and that the drug has very low abuse potential [116]. Acute doses of 40mg and 
60mg (considerably higher than the FDA-approved twice-daily 10mg dose) were associated with 
higher reports of disliking the drug, again indicating unlikely abuse potential [116]. As noted above, 
there were no unusual safety concerns noted in a Phase II trial of smokers [51]. Following FDA 
approval in 2012, Belviq® entered the U.S. market in 2013. Since then, no new safety concerns have 
been noted [114,115]. Overall, based on extensive Phase II and III research with obesity, and initial 
Phase II research in substance use disorder populations, lorcaserin is proposed as a promising 
treatment option for substance use disorders [72].  
Absence of side effects associated with nonspecific serotonergic agents. Past efforts to advance non-
selective serotonergic agents (e.g., fenfluramine/phentermine, fen-phen) for obesity - as well as 
efforts to investigate their efficacy for addiction - were halted due to adverse side effects. However, 
it is important to note that cardiac and psychiatric side effects of fenfluramine/phentermine are 
attributable to activation of 5-HT2B and 5-HT2A receptors. These side effects are not part of the 


 
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UNM IRB Protocol Template v01.19.18 
profile of lorcaserin, which is highly selective for the 5-HT2c receptor. This finding was borne out in 
the Phase III obesity trials: pooled data that included 20,000 echocardiogram readings over two 
years of medication exposure found no evidence for increased risk of cardiac valvulopathy [114,115]. 
Safety profile in participants with substance use disorder. Findings from the first trial of lorcaserin 
for substance use disorder, which aimed to examine the efficacy and safety profile of lorcaserin in 
smokers, were consistent with the aforementioned findings [51]. Smokers in this study were either 
normal weight or overweight, under-weight participants (<18kg/m2) were ruled out due to a lack of 
safety studies in this population. The most commonly reported side effects included headache, 
nausea, dizziness, and constipation. Most AEs were mild or moderate, with no AEs in lorcaserin 
groups exceeding the rate of the placebo group by more than 3.5%. Rates of any AEs and AE-related 
discontinuations were 62%/2.5% and 55%/3.0% in the lorcaserin 10mg BID and placebo groups, 
respectively [51]. No unique safety risks were noted in smokers relative to the results from obesity 
trials. Overall, neither the Phase III obesity trials (totaling nearly 7,800 participants) nor the Phase II 
smoking cessation trial (involving 603 smokers) reported any potential interactions or 
contraindications with nicotine, alcohol or other commonly used drugs. Notably, there are now a 
number of randomized trials underway examining lorcaserin in participants with drug use and 
substance use disorder. A full list of registered randomized trials of lorcaserin can be found at 
ClinicalTrials.gov. 
While we have no reason to expect adverse effects specific to our study population, we plan to 
carefully assess potential side effects to inform the safety profile for this population, and the 
inclusion of a DSMB will maximize safety. Monitoring will be the primary responsibility of the PIs 
and the study physician, who will meet weekly to discuss the status of the trial. In addition, we will 
establish a Data and Safety Monitoring Board to maximize safety. The DSMB will include two 
physician reviewers and an external reviewer. This board will meet at least every six months to 
review data quality, recruitment and retention, and to review all serious or clinically significant 
adverse events. In addition, the board will review safety data following any serious adverse event 
that appears to be study related.  Patterns of adverse events as well as individual events may indicate 
the need for operational changes, protocol modifications, a decrease in dose, or, conceivably, 
discontinuation of the trial. 
Pharmacokinetic and pharmacodynamic profile. According to the prescriber's brochure, lorcaserin 
reaches peak plasma concentrations in 90 - 120 minutes after oral dosing. Steady-state plasma levels 
are achieved after 3 days of twice-daily dosing, and the plasma half-life is roughly 11 hours. Human 
studies have demonstrated that lorcaserin distributes to cerebrospinal fluid and the CNS. Lorcaserin 
is metabolized via multiple enzymatic pathways in the liver and excreted primarily (92%) in urine. 
Its metabolites shows no activity at 5-HT receptors. 
Selected dosage and medication duration. The current study will use the FDA-approved dosage of 
10mg twice- daily (BID). This dosage was used in the recent smoking cessation trial noted above. 
We will use a 7-day medication schedule because a) this allows more than adequate time to reach 
steady-state plasma levels, and b) this time frame allows us to capture short-term changes in 
naturalistic smoking/craving in this sample. Of note, recent data suggest that lorcaserin has acute 
effects on reducing nicotine intake when administered 15 min. prior to testing [45], suggesting that 
short-term medication exposure is adequate to observe effects on addiction-related outcomes. In 
addition, the first neuroimaging study of lorcaserin found differences in neural reactivity to hedonic 
food cues following one week of treatment [117].  


 
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Questionnaire and Interview Assessments. There are potential psychological risks associated with 
assessment procedures. Participants may find the battery of psychiatric and psychological 
assessments tedious or intrusive. Participants may experience discomfort resulting from questions 
about personal histories or substance use patterns.  
Participation in Smoking Sessions. Other potential risks include those related to participation in 
smoking sessions. For example, it is possible that participants may experience dizziness/nausea from 
smoking in the laboratory setting. The might experience temporary discomfort or craving while 
abstaining from cigarettes leading up to the smoking cession. However, the purpose of the laboratory 
procedures is to investigate drug effects on craving, and these procedures are commonly used in 
human laboratory studies. There is also the possibility that participants may experience demand 
characteristics (e.g., feeling obligated to smoke) in laboratory sessions. However, all participants 
will be regular daily smokers, and we have taken measures to protect against ethical concerns by 
excluding treatment-seekers or those engaged in an active quit attempt. Participants will also have 
the option not to smoke if they choose not to. 
Confidentiality/Privacy. Risks from potential breaches of confidentiality include invasion of 
privacy, as well as social and economic risks. Economic risks include alterations in relationships 
with others that are to the disadvantage of the subject, and may involve embarrassment, loss of 
respect of others, labeling with negative consequences, or diminishing the subject's opportunities and 
status in relation to others. There is also a risk of breach of data confidentiality (uncommon). 
There may also be side effects or risks to study participation that are unforeseen and not known at 
this time. 
Plan for Preventing/Minimizing Risks: 
Provisions to Monitor the Data to Ensure the Safety of Subjects: 
Medication and Side Effects Monitoring. Although we anticipate the risk of adverse events to be 
low based on the safety profile of the medication, several steps will be taken to track and report 
medication-related side effects. A project staff member will contact participants during medication 
weeks to assess potential side effects. Participants will be given a contact number for study medical 
staff in case of serious emergent side effects. Participants will return to MRN for repeat follow-up 
examinations (including weight, heart rate/blood pressure measurements, ECG) following the 7-day 
medication phase. All adverse events will be documented and reported in accordance with UNM 
OIRB and MRN policies, applicable FDA regulations, and the regulations of NIH.  
Confidentiality/Privacy. Any computerized data will be password protected and contained on a 
secure, password-protected computer or a secure server. Recruitment data (de-identified) will be 
stored in a secure, password-protected file accessible only to the study investigators and personnel. 
At the end of recruitment, eligible subject files will be separated from those failing to meet eligibility 
criteria, and records of ineligible recruitment subjects will be anonymized. Data pertaining to 
screening failures will be tabulated in an anonymized fashion. Data collected in other formats (e.g., 
medical screening notes) will be labeled only by study identifier and stored in binders in secure, 
locked cabinets while the study is taking place. Files will be stored and archived in accordance with 
Good Clinical Practice (GCP) standards. For all questionnaire and interview assessments, 
participants will be informed that they may decline to answer any question if they so choose.  
Risks Related to Smoking Sessions. To ensure participant safety, a member of the study staff will 
be present for the duration of all smoking sessions, and a member of the study medical staff will be 
on call during smoking sessions. Several steps will be taken to ensure that a potential long-term 


 
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UNM IRB Protocol Template v01.19.18 
cessation attempt is not undermined by participation in the study. First, participants will be screened 
twice (once by phone, and again in person) to ensure that those reporting the intent of an imminent 
quit attempt (i.e., during the next 90 days) are not enrolled. Participants who express desire to 
engage in a permanent quit attempt will be screened out and referred to treatment resources. 
Additionally, any participants who change quit intentions during the study (e.g., initiate a permanent 
quit attempt sooner than anticipated) will be excused from further participation and provided with 
cessation resources. Finally, as a component of informed consent, participants will be informed that 
a) the study involves laboratory cigarette smoking, b) participants are free to withdraw at any time if 
they wish to initiate a permanent quit attempt, and c) participants will be provided with cessation 
resources upon request at any point during the study. Co-I Wilcox, an addiction psychiatrist, will 
provide participants with cessation advice and direct referrals as needed.  
Risks Related to DNA Collection. The purpose of collecting saliva for DNA in this study is to 
allow secondary analyses to examine whether medication effects might be different according to 
certain genetic factors. The main aim of this analysis will be to examine the CYP2A6 gene, which is 
related to nicotine metabolism. These analyses may also focus on genetic factors potentially 
associated with drug use or related behaviors, such as impulsivity. Potential risks associated with 
DNA collection involve potential identification, and there may be risks with genetic (DNA) tests that 
are as yet unknown. Genes may be shown at some point in the future to be related to mental illnesses 
or tendency to addiction. Samples will be labeled with participant ID only, and analyzed at an 
outside laboratory. Samples will be destroyed upon completion of the analyses. We will not conduct 
any whole genome sequencing of the DNA samples.  Additionally, the consent form will state that 
participants have the option to opt out of DNA collection, and to request that their samples are 
destroyed at any time during the study.  Participants will not receive any feedback from any of the 
genetic tests from study staff. 
Compensation for Research-Related Injury. No commitment is made by MRN to provide free 
medical care or money for injuries to participants in this study. This is clearly stated in the consent 
form.  
Economic Burden to Subjects.  Participants will not be charged for any of the experimental study 
procedures. If incidental findings from the study (e.g. abnormal EKG findings or abnormal 
hepatic/metabolic labs) result in the need for further evaluation/treatment, the participant or their 
insurance company will be responsible for additional clinical evaluation/treatment that may be 
needed. Also, incidental finding information is disclosed only to the individual participant. However, 
if a participant chooses to disclose such information to their personal physician, this may become 
part of their medical record which may or may not have an effect in the future on getting health or 
life insurance.  
 
II. 
Benefits  
The participants in this study are not expected to benefit directly from their participation. However, 
the knowledge gained from this study could lead to a better understanding of a medication with 
potential to enhance smoking cessation efforts, and potentially other substance use disorders. Given 
the use of an FDA-approved medication that has been deemed safe in the context of chronic 
administration for weight reduction, the risks to which participants will be exposed during this short 
medication screening trial are deemed relatively small in comparison to the potential benefits of the 
proposed research (i.e., demonstrating potential efficacy of a new medication).  


 
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UNM IRB Protocol Template v01.19.18 
III. Privacy of Participants 
Five private, closed door rooms are available at MRN. The rooms have white noise generators 
outside the doors to prevent conversations from being overheard.  All staff are trained in the HIPAA 
Privacy Rule. 
 
IV. Unanticipated Problems/Adverse Events 
All project staff will be trained to identify adverse events (AEs), which must be reported to the PI 
within 24 hours, and serious adverse events (SAE) must be reported to the PI as soon as possible 
after a staff member becomes aware of an SAE. In addition, any unanticipated participant issues 
will be discussed in weekly staff meetings, which will provide another opportunity to identify AEs. 
Anticipated problems and AEs will be reported to the OIRB within 7 calendar days. 
 
V. Participant Complaints 
If a participant wishes to issue a complaint or request information about the research, they may 
notify any study team member or the site PI, Eric Claus, at (505) 272-5028, Monday – Friday from 
8am – 5pm.  Participants may also contact the UNM Office of the IRB, (505) 277-2644, 
irbmaincampus@unm.edu. Website: http://irb.unm.edu/ 
Depending on the nature of the complaint, the problem will be resolved directly with the 
participant, if possible, in a confidential and timely manner. Complaints that constitute a reportable 
event will be submitted to the IRB within 7 days. Participant complaints will be coded with a 
unique research subject identifier and kept in their respective study folder in a locked office for 
record-keeping purposes.  
 
PROJECT DATA 
I. 
Data Management Procedures and Confidentiality 
 
Consent Forms: Signed consent forms are stored in a locked cabinet in a locked office at MRN.  
Questionnaire Data: All data are coded with a unique research subject identifier (URSI) number.  
Electronic data are stored on a drive only accessible by the research team on a secure server. 
Electronic data captured by RedCap are stored on a secure server at MRN, and identified by participants ID 
only. For non-computer based forms, such as the neuropsychological assessments, the data collection 
sheets are stored in a locked cabinet in a separate locked data storage space at MRN. 
Behavioral Data: All data are coded with the URSI, and collected and stored electronically.  
Electronic data is stored on a drive only accessible by the research team on a secure MRN server.  
De-identified data resulting from this study may also be presented at meetings, published in 
journals/books, used in classrooms for training/teaching purposes, and may be shared with other 
researchers including scientists at other universities and institutions. In addition, this study will be 
registered at ClinicalTrials.gov, and de-identified information from this study will be submitted to 
ClinicalTrials.gov. 
Data and safety monitoring plan: See attached plan. 
 
Certificate of Confidentiality: In addition to the above protections, this study has a Certificate of 
Confidentiality from NIH to further protect participant confidentiality. Importantly, as stated in the 
consent, participants are informed that if they report current abuse of a child or an elder, we will 
report the person to the proper authorities, consistent with New Mexico state law. 
 
Finally, participants will be given the option of having all their data  (behavioral assessments) stored 
in the MRN Data Repository (UNM HRRC# 06-387, PI: Roberts). 


 
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UNM IRB Protocol Template v01.19.18 
 
 
II. 
Data Analysis/Statistical Considerations 
Primary and secondary outcomes will be evaluated using mixed linear effects models with condition 
(lorcaserin, placebo) as a within-subjects factor and medication order as a between-subjects factor. 
Maximum likelihood estimation will be used to account for missing data by analyzing all available 
cases. The primary outcomes are 1) minutes of resistance to smoking reinstatement and 2) number of 
half cigarettes smoked during the ad lib session.  Using the same model, we will also examine 
secondary outcomes including: impulsive choice (k value from monetary discounting task and 
cigarette discounting task), impulsive action (commission errors on CPT), and reward response bias 
as measured by the Reward Responsiveness Test. 
Statistical Power. To achieve adequate power (.80) to detect medium effects of medication on our 
primary outcomes, we will recruit a sample of 42 smokers in order to arrive at a final sample of 34 
(allowing for up to 20% attrition). Given no prior data on lorcaserin’s effects on laboratory 
outcomes, we reviewed effects reported in similar screening studies with other medications. In a 
study using the lapse paradigm proposed here, varenicline had a medium to-large effect on duration 
to reinstatement (Cohen’s d = .72) and a large effect for self-administration (d = 1.5). To account for 
the possibility of stronger effects for varenicline relative to lorcaserin, our power analyses assumed a 
medium effect size. We assumed a within-subjects correlation of 0.60 for laboratory outcomes (as 
reported in prior human laboratory screening studies) and an alpha level of .05. We estimated power 
in G*Power software using a fixed effects, within-subjects design and two time-points. 
Conservatively, a sample of N = 34 allows sufficient power (.80) to detect a medium effect on the 
primary outcomes (Specific Aims 1 and 2). Although human data are not available to inform the 
predicted effect size for Aim 2, preclinical studies using this medication, and an analogous 
behavioral task, suggest large effects of medication. For our supplementary aim (evaluating indirect 
effects on the primary outcomes via impulsivity and craving), simulation studies indicate that the 
proposed analysis, utilizing a bootstrap procedure, will provide sufficient power (.80), given the 
planned sample size, to detect mediated effects in medium-to-large effect size range. 
Participant Withdrawal 
Participants may withdraw from the study at any time.  The PI may choose to withdraw 
participants from the study if the participant’s status changes (e.g., health change, becomes 
incarcerated), is suspected of intentionally providing false data, or other reasons that would 
lead to poor data quality (e.g., very poor performance in impulsivity tasks).  Data from 
withdrawn participants will be evaluated on a case by case basis.  For participants that 
withdraw themselves from the study, we will use data they provided prior to withdrawing.  If 
the PI chooses to withdraw the participant, data will only be used if it meets quality control 
standards (e.g., adequate behavioral performance, limited missing data).  
 
PRIOR APPROVALS/REVIEWED AT OTHER IRBS 
 
MRN Departmental Review 
 
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UNM IRB Protocol Template v01.19.18 
Measures (listed alphabetical): 
Alcohol Purchase Task 
AUDIT 
Cigarette Evaluation Scale 
CES-D 
Contemplation Ladder 
Cigarette Purchase Task 
Daily Survey 
Demographics form 
Fagerstrom Test for Nicotine Dependence 
Locator form 
Monetary Choice Questionnaire 
Minnesota Nicotine Withdrawal Scale 
Nicotine Dependence Syndrome Scale 
Positive and Negative Affect Scale 
Reward Based Eating Drive Scale 
Self Rating of the Effects of Alcohol Questionnaire 
Simplified Nutritional Appetite Questionnaire 
Three Factor Eating Questionnaire 
Tiffany Questionnaire of Smoking Urges 
UPPS-P Impulsivity Questionnaire 
 
Data Collection Forms: 
Study Med Count 
Vitals 
Conconcomittent Meds 
Medical History 
Physcial Exam 
SAFTEE 
 
 
Other 
SAE Report 
SAE Report follow-up 
Adherece Handout 
Belviq prescribing information 
Lexicomp report for lorcaserin 
MRN Departmental Review Form 
Grant application 
Data safety monitoring plan 
 
 
 

ICF_001.pdf: 
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MIND RESEARCH NETWORK 
CONSENT TO PARTICIPATE IN RESEARCH 
 
Lorcaserin effects on smoking behaviors 
 
You are being asked to participate in a research study. The box below highlights key information about this 
research for you to consider when making a decision about whether or not to participate. This form will 
explain the study to you, including the possible risks as well as the possible benefits of participating, so you 
can make an informed choice about whether or not to participate in this study.  Please read this consent form 
carefully. Ask the investigators or study staff to explain any words or information that you do not clearly 
understand.  
 
Key Information for You to Consider 
• 
You are being asked to participate in a research study about how the medication lorcaserin 
affects smoking-related behaviors (such as cigarette craving and decisions about smoking) and 
behavioral factors related to smoking (such as impulsive responding). Participation is 
voluntary and it is up to you whether or not you choose to participate. 
• 
Your participation is expected to last about 18 hours over 5 weeks. This will include up to 5 
study visits, with an additional 30-60 min. over the phone.   
• 
During the study you will answer questions in interview and computerized format, perform 
computerized tasks, take the study medication and placebo pills, and complete two sessions in 
which you will have the opportunity to smoke cigarettes. 
• 
You will also complete some medical tests such as collection of blood samples, collection of 
urine, and breath alcohol (to detect recent alcohol use) and breath carbon monoxide (to detect 
recent cigarette use) tests 
• 
The primary potential risks of this study include boredom, discomfort and fatigue from study 
procedures, and potential side effects from the medication. 
• 
You are not expected to receive any specific benefits from participating.  
• 
This is not a treatment study. 
• 
Taking part in this study is voluntary so you can choose not to participate.  
 
Purpose and General Information 
You are being asked to participate in a research study that is being done by Eric Claus, Ph.D., and Christian 
Hendershot, Ph.D. who are the Principal Investigators (PIs). This research is being done to evaluate how the 
medication lorcaserin affects cigarette smoking and related responses (e.g., craving). Lorcaserin is approved 
by the Federal Drug Administration (FDA) for the purpose of weight management. The medication is 
typically prescribed to help people who have a body mass index (BMI) over 30 lose weight. Research in 


V1.4 09/10/19 
 
 
 
 
 
 
 
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animal studies has also shown this medication may influence responses to nicotine and decision-making 
tasks. This study also will try to identify, using questionnaires and computerized tasks, whether lorcaserin 
influences responses to nicotine in certain groups of people. This study is not a treatment study. 
 
You are being asked to participate in this research study because you report smoking cigarettes at a level that 
meets criteria for “dependence,” you express interest in eventually quitting, and you report that you are not 
actively planning to quit in the next several weeks. Up to 100 people will be enrolled into the study to obtain 
a final sample of approximately 40-50 people; this study will take place at the Mind Research Network. This 
study is funded through the National Institute on Drug Abuse (a division of the National Institutes of Health). 
 
What will happen if I participate?  
If you agree to be in this study, you will be asked to read and sign this consent form. You can discuss any 
questions you may have about this form with the study staff. After you sign the consent form, the following 
things will happen:   
 
You will answer a series of questions about your alcohol use, cigarette use, and medical history, as well as 
other questions to make sure that you’re eligible for the study. You will also meet with a member of the 
study staff to complete a medical history interview, as well as some brief assessments (e.g., breath carbon 
monoxide, blood pressure, etc.), height/weight measurement, and heart function (described below). 
 
If you are eligible for the study, you will be asked to take the active medication for approximately one week, 
and placebo pills for approximately one week (a placebo is a pill that looks like the active medication, but 
has no active medication in it). The order in which you take the pills will be randomized, meaning that some 
people will take the active medication the first week and the placebo during the second week, and some 
people will take the placebo the first week and the active medication the second week. Randomization means 
you will be assigned to a group based on chance, like a flip of a coin. Neither you nor any member of the 
research team chooses your assigned group or will know what group you are assigned to, however, in an 
emergency (e.g., if you are hospitalized or in an accident and knowing the drug would be important for your 
treatment), the study doctor can get this information. 
 
Participation will occur over the course of roughly 5 weeks, and will include a total of approximately 5 visits 
to MRN (approximately 16-18 hours total), including 1 hour over the phone (roughly 4, 15-minute calls). 
The study visit schedule is as follows: 
 
• 
One screening visit (today) to complete the consent process, eligibility interviews, and medical 
assessment (2-3 hours). (Note: the medical assessment may be conducted on a separate day to 
accommodate scheduling.) 
• 
If you are eligible after the screening visit, you will then complete a baseline visit (2-3 hours). At this 
visit you will complete additional questionnaires and computerized tasks, and receive the first set of 
study pills (active medication or placebo).  
• 
Follow-up visit 1 (up to 5 hours). After taking the first set of study pills for roughly one week, you will 
complete a follow-up visit that includes a repeat medical assessment, a blood draw, as well as follow-up 
questionnaires and computerized tasks. This visit will take place after you have taken the study pills for 
roughly one week. This visit will also include a cigarette smoking session (described in more detail 
below). 
• 
Next, you will have a medication break (no pills or study visits) for at least 7 days. 


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• 
Medication refill visit (1 hour). This appointment will take place about 1-2 weeks after follow-up visit 
1. At this appointment you will be asked to complete some follow-up questionnaires and medical 
assessments (e.g., weight, blood pressure), and will receive the next set of study pills (active medication 
or placebo). 
• 
Follow-up visit 2 (up to 5 hours). This visit will take place after you’ve taken the second set of study 
pills for roughly one week. The study visit procedures will be identical to follow-up visit 1. 
• 
Telephone check-ins (5-15 minutes each, total of 4 check-ins): During weeks when you are taking the 
study pills, a member of the study staff will call you on the phone to ask about potential side effects, as 
well as alcohol and nicotine use. 
 
If you are unable to commit to the timeframe of the study (6 weeks) or if you plan to travel out of town, you 
should let us know, as this will make you ineligible for participation.  
 
We have organized the different parts of the study into three categories (Screening visit, Baseline visit, 
Medication weeks, and Follow-up visits), described in more detail below. 
 
I. Screening Visit 
 
As part of screening to see if you qualify for the study, we will ask you about your current and previous 
smoking history, and conduct a structured interview asking you about your other substance use and medical 
history. You will meet with a member of our medical staff, and we will ask you to complete some brief 
assessments, including expired carbon monoxide (CO), heart rate/blood pressure, body weight/height, a 
blood sample (approximately 4 teaspoons), and an electrocardiogram (ECG) to measure heart function. You 
will be asked to provide a urine sample to test for the presence of several drugs, including cocaine, heroin, 
methamphetamine, and marijuana. You will be able to collect the sample in a bathroom without anyone 
watching you. For females, this urine test will also be used to complete a pregnancy test (as a safety 
precaution). If your pregnancy test shows a positive result at any point during the study, we will tell you this 
result in a private room.   If you test positive for drugs (other than marijuana) or pregnancy, you will not be 
eligible for the study.  These tests are mostly used to make sure it is safe for you to take the study 
medication. The blood sample will be checked for kidney function, electrolytes, liver function, nicotine 
metabolites, and blood cell counts.  Your urine sample will also be saved and analyzed to measure levels of 
nicotine and nicotine metabolites. If the tests on your blood sample are abnormal or if your ECG or vital 
signs seem abnormal, the study's medical staff will notify you of the findings; you will not be notified about 
any genetic results.   
 
Saliva Collection. Finally, we will ask you for a saliva sample to collect genetic material (genes or DNA). 
We will provide you with a small cup and ask you to fill it with saliva up to a certain line (less than half a 
teaspoon). The purpose of collecting saliva for DNA in this study is to examine whether medication effects 
might be different according to certain genetic factors. Your saliva will be labeled only with a special 
number (code), which will remain linked to your identity. We will store this sample until we are ready to 
analyze it. If you agree, we may keep your saliva for a very long time (indefinitely) for future research.  
Please see optional procedures at the end of this consent form.  
 
The screening procedures are expected to take up to 3 hours. Depending on scheduling, you may be asked to 
return to complete the medical assessment at a separate visit (resulting in two 1.5 hour visits).  
 
II. Baseline Visit 


V1.4 09/10/19 
 
 
 
 
 
 
 
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If you are eligible after the screening visit and wish to participate, you will be asked to return for a baseline 
visit. During this visit you’ll be asked to complete a number of computerized questionnaires (about smoking 
history, substance use, personality, etc.), and do some computerized tasks (to measure things such as 
impulsive responding and reward-based responding). Women will complete a urine pregnancy test again 
before receiving any medication.  You will be asked to provide a saliva sample for DNA analysis (see 
genetic analysis section below). You will also receive your first set of study pills along with instructions on 
how to take them. This visit is expected to take around 2-3 hours.  
 
III. Medication Weeks 
 
You will be asked to take each type of study pill (active medication or placebo) for 7 days each, with a break 
of at least 7 days in between. At the end of this 7-day break, you will complete a brief visit to MRN to pick 
up the second set of study pills. During each of the medication weeks, you will be asked to take the study 
medication (consisting of 2 pills daily), and to complete a daily log to record the number of pills taken, 
potential side effects, cigarette use, other drug use, cravings, and questions related to eating/hunger. 
Additionally, a member of the study team will contact you at two scheduled times (e.g., 2 and 4 days after 
starting the medication) to review your medication-taking and any side effects by telephone. These calls are 
expected to last 5-15 minutes each.  
 
IV. Follow-up Visits 
 
Each of the medication weeks will end with a follow-up visit to MRN (i.e., Follow-up Visits 1 and 2). These 
sessions will require that you spend most of the day in the lab (up to 5 hours). Additionally, these visits will 
require overnight abstinence from smoking. We will ask you refrain from smoking starting at midnight the 
night before the visits. When you arrive at the lab, you will take a CO test by blowing into a machine to 
confirm overnight abstinence. If the CO test does not show recent abstinence, your visit may be rescheduled. 
If the test shows abstinence, you will receive a monetary bonus (see compensation section).  
 
You also must agree not to consume alcohol or use recreational drugs within 24 hours of these visits, and not 
to eat for 4 hours before arriving at MRN. After arriving, you will be asked to provide a urine sample for a 
urine drug test and a breath alcohol reading to confirm recent abstinence from alcohol and drugs. For 
females, the urine sample may also be used for a pregnancy test. If you test positive for recent use of 
recreational drugs (with the exception of marijuana) you may be rescheduled or withdrawn from the study.  
The urine will also be tested to determine whether you have been taking the medication.  The medication 
includes a small amount of riboflavin, a substance that can be detected in urine.   If you have not taken the 
medication for the prior week, you may be rescheduled or withdrawn from the study.  We will also collect a 
blood sample (approximately 4 teaspoons at each follow-up visit) that will be used to detect whether you 
took the medication for the week. 
 
At these visits you will complete brief follow-up interviews with the study staff and a member of the medical 
team, about your smoking behaviors, craving, and eating habits. You will be asked to complete follow-up 
computerized questionnaires and tasks, similar to the baseline session. You will also be asked to repeat the 
brief medical assessments from the baseline session (weight, heart rate/BP) and will be asked about any side 
effects you have experienced. In the event that the study medical staff members have any reason to believe 
that continuing to participate in the study would not be safe for you, you may be removed from the study. 
 


V1.4 09/10/19 
 
 
 
 
 
 
 
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Smoking session. Each of the two follow-up visits will include a smoking session. For these sessions we will 
ask that you bring one unopened package of your preferred brand of cigarettes. First, you will be asked to 
light a cigarette without smoking it, and to complete questionnaires about your mood and craving. Next, you 
will have the opportunity to smoke cigarettes or to delay smoking. Finally, you will have the opportunity to 
smoke additional cigarettes if you wish. The smoking session will last 1-2 hours. You do not have to smoke 
during this session, but the session will last the same amount of time whether you choose to smoke or not. 
 
What are the possible risks or discomforts of being in this study? 
Medication. There are certain risks/side effects of the study medication. In studies where lorcaserin was 
taken for a longer period of time (at least one year), the most commonly reported side effects (i.e., greater 
than 5% of participants and more common than placebo) included: 
 
• 
headache 
• 
dizziness 
• 
fatigue 
• 
nausea 
• 
dry mouth 
• 
constipation 
• 
nasopharyngitis (nasal/throat irritation, similar to a common cold) 
 
Additionally, the less common side effects (reported by 2% or more of patients) included: 
 
• 
diarrhea 
• 
vomiting 
• 
upper respiratory tract infection 
• 
urinary tract infection  
• 
back pain 
• 
musculoskeletal pain 
• 
cough 
• 
oropharyngeal pain (e.g., sore throat) 
• 
sinus congestion 
• 
rash 
 
A full summary of safety information and potential side effects is included in the medication brochure that 
you have received today. We encourage you to pay attention to any potential side effects you might 
experience. We will check for side effects at every visit and the study medical staff (physician or nurse 
practitioner) may choose to discontinue the medication if you are showing signs of serious side effects. You 
will also receive a phone number to contact medical staff on the study with any questions. If you visit a 
physician or are prescribed any medications while enrolled in this study, you should inform your physician 
that you will be taking lorcaserin while participating.   
 
Blood Draw. Drawing blood may cause temporary pain and discomfort from the needle stick, occasional 
bruising, sweating, feeling faint or lightheaded, and in rare cases, infection or nerve pain. 
 


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Smoking Session. It is possible that smoking cigarettes can lead to temporary symptoms such as dizziness, 
or nausea. You do not have to smoke at the follow up visits. It is also possible that you might experience 
temporary discomfort or withdrawal symptoms while abstaining from smoking overnight. 
 
Interview and Questionnaire Responses. It is possible you could experience emotional stress, 
inconvenience or an invasion of privacy when answering questions in this study. However, you may refuse to 
answer any questions or perform any test that you do not wish to answer or do. 
Every effort will be made to protect the information you give us. However, there is a small risk of loss of 
confidentiality that may result in stigmatization. Additionally, there may also be side effects or risks to study 
participation that are unexpected and not known at this time. Procedures we will use to protect the 
information you give us are described below. 
 
Genetic Analyses. DNA samples will be labeled with a number only (not your name) and analyzed at an 
outside laboratory. The main aim of this analysis will be to examine the CYP2A6 gene, which is related to 
nicotine metabolism. These analyses may also focus on genetic factors potentially associated with drug use 
or related behaviors.  The risks associated with genetic (DNA) tests are unknown. Genes may be shown at 
some point in the future to be related to mental illnesses or tendency to addiction. Since in some cases the 
results of these genetic tests may allow us to predict the risk of getting an illness, we will keep the results 
confidential (only scientists working on this research project will know the results). There may also be 
unexpected risks connected with this type of testing.  At some point in the future, your genetic information 
could be used to identify you; however, we have put precautions in place to help reduce this risk. We will not 
complete whole genome sequencing on your DNA sample. We will take every measure to protect you from 
the risks of other people finding out about the results of your genetic tests, which include people like 
insurance companies or future employers.  
 
There are risks of loss of privacy, getting insured, being employed, and stigmatization (treated badly due to 
your genetic testing results).  There are some protections afforded by the Genetic Information 
Nondiscrimination Act (GINA). For a detailed list of protections, please read the GINA information sheet on 
our website at http://www.mrn.org/about/policies/ or ask the research team for a copy. 
 
Unforeseeable risks.  The particular treatment or procedure may involve risks to the participant (or to the 
embryo or fetus, if the participant becomes pregnant) that are currently unforeseeable. 
 
How will my information be kept confidential? 
We will take measures to protect your privacy and the security of all your personal information. Your name 
and other identifying information will be maintained in locked files and/or restricted databases, available 
only to authorized members of the research team for the duration of the study.  All of the information we 
collect about you will be coded with a unique research subject identifier (URSI) or other subject code and 
will be kept on password protected computers, and stored securely in restricted and protected databases 
according to MRN information security policies. The record linking your name to your study ID number will 
be kept indefinitely (forever) at the MRN in a confidential manner so that you may continue to have access to 
your information. De-identified data (meaning data that cannot be traced back to you) from this study may 
also be presented at meetings, published in journals/books, used in classrooms for training/teaching purposes, 
and may be used and shared with other researchers for future research purposes, which includes scientists at 
other universities and institutions. However, your name and other identifying information will never be used 
in any published reports about this study. 
 


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The urine and blood samples will be labeled with your URSI number and date of study visit and stored in a 
secure freezer at MRN.  These samples will be stored indefinitely until we are able to send all samples for 
analysis. The blood and urine samples collected at the screening visit will be sent to an outside laboratory for 
analysis. 
 
Your DNA sample will be stored with an URSI to protect your identity. Your name and other identifiable 
information will be linked to the URSI but will not be present on stored samples. If you agree, your sample 
may be used for future undetermined research.  It will be stored at the Mind Research Network or another 
secure storage facility indefinitely or until it has been completely used. You may request that your DNA 
sample be destroyed by providing a written request or phone call to the research team listed on this consent 
form. It is possible we will not be able to destroy your sample if the link to your identity has already been 
removed because your personal information is no longer associated with your sample. 
 
To help us protect your information, this research study has a Certificate of Confidentiality from the National 
Institutes of Health (NIH). With this Certificate, the research team cannot be forced to provide your name or 
any identifiable research data or specimens to people who are not connected with this study, including 
Federal, state or local authorities, even under a subpoena. The protection offered by the certificate does not 
stop us from reporting information about suspected or known sexual, physical, or other abuse of a child or 
older person, or that you plan to harm yourself or someone else. If any member of the research team is given 
such information, we will make a report to the appropriate authorities.  
Information from your participation in this study may be reviewed by MRN, federal and state regulatory 
agencies, the Food and Drug Administration (FDA), and by the University of New Mexico Institutional 
Review Board (IRB) which provides regulatory and ethical oversight of human research. Also, because this 
research it sponsored by NIDA, staff from that and other DHHS agencies may review records that identify 
you only for audit or program evaluation.  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time. 
 
What are the benefits to being in this study? 
There are no expected direct benefits for participating in this study. However, knowledge gained through this 
study may aid the development of more effective treatments for smoking.  
 
What other choices do I have if I don’t participate? 
Taking part in this study is voluntary so you can choose not to participate. If you would like to receive a list 
of referral options for alcohol or smoking cessation treatments, we will provide one to you. 
 
New information that may impact your decision to participate 
You will be informed of any significant new findings that become available during the course of the study, 
such as changes in the risks or benefits resulting from participating in the research or new alternatives to 
participation that might change your mind about participating. If any new information related to the 
medication used in the study becomes available, study staff will inform you of the new information and you 
will be able to discuss this information with the PI or study physician to determine whether it changes your 
decision to participate. 
 
 


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Are there any costs to me for participating? 
You will not be charged for any of the experimental study procedures. You will be asked to bring a package 
of your cigarettes to the follow up visits, and to use your own cigarettes during the smoking session. This is 
only to ensure that you will be smoking your preferred brand of cigarettes. 
 
Will I be paid for taking part in this study? 
In return for your time when participating in this study, you will be paid up to $500 total in cash for 
participation. The payments are as follows: $50 for completing the screening visit, $60 for the baseline visit; 
$100 for completing follow-up visit 1 (plus an extra $30 bonus for showing overnight abstinence); $150 for 
completing the medication refill visit and follow-up visit 2 (plus an extra $30 bonus for showing overnight 
abstinence). Between follow-up visits 1 and 2, you will need to come to MRN to pick up your medication 
refill. You will also receive a $30 bonus for completing at least 75% of scheduled phone-check-ins, and a 
final bonus of $50 for completing all of the study visits (to be paid at the final visit). In the event you are not 
able to pick up your final cash payment in person, we can also send the final payment via electronic gift card 
to your email address. 
 
Compensation for participation in research is considered taxable income and should be reported on your 
income tax return. If you earn $600 or more participating in MRN research studies, you will be sent a W-9 
form to collect your tax information which will be reported to the Internal Revenue Service (IRS) as required 
by law. The information provided to the IRS will not disclose your participation in a research study; instead 
the income will be listed as “nonemployee compensation.”  
 
If MRN and/or the investigators develop intellectual property and/or commercialize products or services, 
directly or indirectly, based on the results of the research done with your data, there are no plans to provide 
you with any financial compensation. 
 
Can I stop being in the study once I begin? 
Yes. You can withdraw from this study at any time without affecting your access to care, education, or other 
services to which you are entitled. If you decide you would like to stop the study medication during the 
study, please let the medical staff/team know as soon as possible and we will help you discontinue it. 
 
The investigators have the right to end your participation in this study if they determine that you no longer 
qualify to take part, if you do not follow study procedures, (e.g., you do not abstain from alcohol prior to the 
follow-up visits or test positive for recreational drugs at the follow-up visits), or if it is in your best interest or 
the study’s best interest to stop your participation. NIDA may stop the study at any time. 
 
What will happen if I am injured or become sick because I took part in this study? 
If you are injured or become sick as a result of this study, any emergency treatment will be at your cost.  No 
commitment is made by the MRN or UNM to provide free medical care or money for injuries to participants 
in this study.   
 
It is important for you to tell the Principal Investigator or study physician immediately if you believe you 
have been injured or become sick because of taking part in this study.   
 
Refusal to Sign 


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If you choose not to sign this consent form, you will not be allowed to take part in the research study. 
 
What if I have questions or complaints about this study? 
If you have any questions, concerns or complaints at any time about the research study, Eric Claus, Ph.D., or 
his associates will be glad to answer them at 505-272-5028. If you would like to speak with someone other 
than the research team to obtain information or offer input, or if you have questions regarding your rights as 
a research participant, please contact the IRB. The IRB is a group of people from UNM and the community 
who provide independent oversight of safety and ethical issues related to research involving people: UNM 
Office of the IRB, (505) 277-2644, irbmaincampus@unm.edu. Website: http://irb.unm.edu/  
 
Consent  
You are making a decision whether to participate in this study. Your signature below indicates that you read 
the information provided (or the information was read to you). By signing this consent form, you are not 
waiving any of your legal rights as a research participant. 
________________________________________________________________________________ 
OPTIONAL: 
We would also like to request your permission to store all of the data that was collected in this study in The 
Mind Research Network Data Sharing Repository for other, future research. The stored data will include 
information such as your age and gender, as well as assessment data that were collected about you during the 
course of this study. It is possible that this information may remain linked to your name. It will be handled 
with the same care and confidentially as it is for the current study. Research done with information from the 
data repository could lead to improved diagnostic and treatment interventions for illnesses and brain 
disorders. If published, results will be presented in summary form only and will not include your name or 
other identifying information. If MRN develops intellectual property and/or commercialize products or 
services, directly or indirectly, based on the results of the research done with your data, there are no plans to 
provide you with any financial compensation.  
 
You have my permission to store my data in the MRN Data Sharing Repository for future research. Please 
initial next to your choice below.    
YES 
 
________ Initials 
NO 
 
________ Initials 
 
We would like to request your permission to contact you for participation in future studies at the Mind 
Research Network.  If you agree, your contact information may be shared with other scientists at MRN.  
 
You have my permission to contact me about participation in future research studies. Please initial next to 
your choice below.   
YES 
 
________ Initials 
NO 
 
________ Initials 
  
 
I have had an opportunity to ask questions and all questions have been answered to my satisfaction. By 
signing this consent form, I agree to participate in this study. A copy of this consent form will be provided to 
me. 
_____________________________                    __________________________/_______ 
Name of Adult Participant (print)  
   
Signature of Adult Participant     Date 
 


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I have explained the research to the participant and answered all of his/her questions. I believe that he/she 
understands the information in this consent form and freely agrees to participate.  
 
______________________________                     ______________________________/ _____ 
Name of Research Team Member                           Signature of Research Team Member/Date