Conditions: Effects of Family History of Alcoholism and Sex on Alcohol Analgesia
Keywords: alcohol effects pain
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 125
Healthy volunteers: yes

Brief summary:
Self-medication of pain with alcohol is a common, yet risky, behavior. Evidence suggests family history of alcoholism may affect the degree to which alcohol use relieves pain, but the independent contributions of expectation and conditioning have not been previously studied. Interactive effects of sex and family history are also currently unclear. This project addresses this gap in knowledge and will inform further research and clinical/translational efforts for reducing risk associated with these behaviors.

Detailed description:

Arms:
arm 1: People reporting at least one parent with a history of alcohol problems. arm 2: People who do not report having a parent with a history of alcohol problems.

Interventions: intervention 1: Ethanol intervention 2: Placebo
Intervention descriptions: intervention 1: A beverage containing dose of ethanol individually determined to raise a participant's breath alcohol concentration up to approximately 0.08 g/dL. intervention 2: A beverage that does not meaningfully increase breath alcohol concentration.

Protocol document:
Prot_SAP_ICF_000.pdf: 
Official Title: Characterizing the Effects of Family History of Alcoholism on 
Alcohol Analgesia 
 
NCT: 04925076 
 
Version Date: 4/5/2023 


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Protocol 
1. Project Title:  
 
Characterizing the Effects of Family History of Alcoholism on Alcohol Analgesia 
 
2. Investigator(s):   
 
Michael Robinson, PhD (PI) 
Sara Nixon, PhD (Co-I) 
Song Lai, PhD (Co-I) 
Jeff Boissoneault, PhD (Co-I) 
 
3. Abstract:  
 
Pain is the most common reason that patients seek medical attention. Acute pain is an 
essential indicator of current or impending tissue damage. However, chronic pain is a 
maladaptive state with strong affective, biological, and psychological components. 
Chronic pain is extremely costly and has strong negative effects on sufferers’ quality of 
life. Existing treatments for chronic pain, including opioid analgesics, are relatively 
ineffective. Perhaps as a result of the lack of efficacious treatments, it has been recently 
reported that nearly 25% of individuals suffering from chronic oral and/or 
musculoskeletal pain self-medicate through the oral consumption of alcohol. Indeed, 
alcohol interacts with a wide range of relevant pharmacologic targets capable of 
modulating the experience of pain. However, the biological mechanisms underlying this 
intuitive interaction are not well established. This relationship is important to understand 
because alcohol analgesia may act as a potent negative reinforcer for alcohol intake, 
which, in turn, can have adverse health effects by increasing risk of developing an 
alcohol use disorder. Familial risk for alcoholism, along with sex and certain 
mood/personality factors, may act as critical modulators of individual sensitivity to 
alcohol analgesia. However, it is currently unclear whether this sensitivity is the result of 
neurobiological, and/or learned factors. By characterizing independent contributions of 
each of these factors, this proposal will improve understanding of the interplay between 
pain/alcohol sensitivity, sex, and family history of alcoholism as a modulator of 
sensitivity to alcohol analgesia. These efforts will inform further research and 
clinical/translational efforts regarding risk associated with self-medication of pain by 
consuming alcohol. Critically, the impact of these factors on the functional neural 
correlates of alcohol analgesia will also be determined, improving mechanistic 
understanding of alcohol analgesia.  
 
4.   Background: 
 
Introduction and Clinical Relevance. Pain is a nearly ubiquitous experience. While acute 
pain is an essential indicator of current or impending tissue damage, chronic pain is a 
maladaptive state associated with biopsychosocial dysfunction. Nearly 100 million 
Americans suffer from chronic pain, which greatly burdens our healthcare system; 


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recent estimates suggest yearly expenditures reach $635B in treatment expenses and 
lost productivity in the United States alone (Institute of Medicine, 2011). Existing 
treatments for chronic pain, including opioid analgesics, are relatively ineffective (Noble 
et al., 2010). Meanwhile, nearly 25% of individuals suffering from chronic orofacial 
and/or musculoskeletal pain self-medicate through the oral consumption of alcohol 
(Riley and King, 2009). Alcohol interacts directly or indirectly with a wide range of 
neurotransmitter systems, including the serotonergic, glutamatergic, and opioidergic 
systems, providing a wide range of relevant pharmacologic targets capable of 
modulating the experience of pain (Vengeliene et al., 2008). As noted by the National 
Institute on Alcohol Abuse and Alcoholism (2013), this behavior is risky for several 
reasons: 1) interactions between alcohol and pain medications may have severe health 
consequences; 2) patients self- medicating pain with alcohol may exceed moderate 
drinking guidelines, increasing the risk of alcohol-related consequences including 
development of alcohol use disorders (AUDs) or painful alcohol-related small fiber 
neuropathies; and 3) alcohol withdrawal itself is associated with increased pain 
sensitivity. Indeed, the health- related consequences of alcohol use and misuse by 
themselves are estimated to cost over $200B per year (Spanagel, 2009). Given that 
25% of treatment seeking alcoholics report past-month pain, and 25% of chronic pain 
patients report heavy drinking (Zale et al., 2015), it is likely that the adverse effects of 
self-medicating pain by consuming alcohol are responsible for a portion of the cost 
associated with both conditions. Mechanisms underlying alcohol analgesia, including 
critical modulating factors, are poorly understood. In order to better understand these 
mechanisms, their interaction with neural adaptations involved in the transition from 
acute to chronic pain, and their implications for patient education, screening, care, and 
management, systematic study of alcohol analgesia is needed.  
 
Mechanisms of Pain. Acute pain is a centrally mediated sensation driven primarily by 
nociceptive input conducted by Aδ and C fibers responding to noxious stimulation or 
tissue injury in the periphery. An individual’s experience of pain is modulated by the 
activity of a well-characterized set of neural structures involved in the contextualization 
and evaluation of the nociceptive stimulus, including those involved in sensory 
processing (primary and secondary somatosensory cortices), executive control 
(prefrontal and anterior cingulate cortices, anterior insula), and limbic processing 
(amygdala, hippocampus) (Apkarian et al., 2005; Clarke and Lawrence, 2013; Craggs et 
al., 2007; Staud et al., 2008). In 80-90% of cases, acute pain resolves as peripheral 
damage is repaired. In some cases, however, patients’ pain persists even after no 
peripheral damage remains. In order to capitalize on the high degree of controllability 
and repeatability afforded by laboratory pain induction techniques, we propose the use 
of experimental heat pain stimulation for this project. This is a common technique used 
to assess pain psychophysics and neural mechanisms of pain which our research group 
has successfully employed many times (e.g., Craggs et al., 2012; Letzen et al., 2015; 
Sevel et al., 2015a; Sevel et al., 2015b).  
 
Relief of Pain as Reward. Because pain is, by definition, an aversive sensation 
(International Association for the Study of Pain, 1979), the cessation of pain is 
associated with relief. Although conceptually distinct from typical appetitive rewards like 


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palatable food or drugs of abuse, substantial similarity between neurobehavioral 
responses to relief and appetitive rewards has been reported (Leknes et al., 2011; 
Seymour et al., 2005; Tanimoto et al., 2004; Ursu and Carter, 2005). For instance, 
Leknes and colleagues (2011) used a task designed to elicit reward associated with 
relief by presenting a warning signal for an intensely painful heat stimulus that was 
followed by a relief signal 50% of the time. In the same study, participants were tasked 
with imagining pleasant scenarios (e.g., “Imagine having your favorite meal”) or neutral 
ones (e.g., “Imagine drinking lukewarm water”). Analyses of both relief and appetitive 
reward were associated with activation in the ventromedial prefrontal cortex (vmPFC) 
and rostral anterior cingulate cortex (rACC), although they were distinguished by 
activations in right anterior insula, bilateral cerebellum, thalamus, and posterior 
cingulate. A follow-up study by the same group, distinguished primarily from the 2011 
study by its contrast of neural responses to moderately painful heat stimuli presented in 
the context of relative relief (i.e., a less painful stimulus than expected), found that 
stimuli less painful than expected were associated with pleasure instead of 
unpleasantness (Leknes et al., 2013). Previously noted functional activations associated 
with relief reward in vmPFC and rACC were replicated, along with medial orbitofrontal 
cortex (mOFC). The importance of these regions in the experience of relative reward 
has also been demonstrated in studies of regarding hedonic aspects of monetary loss 
and gain in both humans and non-human primates (e.g., Padoa-Schioppa and Assad, 
2008; Seymour and McClure, 2008; Tremblay and Schultz, 1999). Critically, it has been 
suggested that appetitive rewards are more reinforcing when simultaneously providing 
relief (Cabenac, 1979; Leknes et al., 2011). It seems likely this is due to the synergistic 
combination of positive and negative reinforcing effects and suggests self-medication of 
pain using alcohol may represent a “double-hit” of reinforcement, thereby increasing risk 
of developing an alcohol use disorder.  
 
Acute Alcohol Effects. The effects of acute alcohol intake at legally intoxicating levels 
(i.e., BAC ≥ 0.08 g/dL) on neurobehavioral function are well documented. A 
comprehensive review of these effects is beyond the scope of this application (see 
Boissoneault et al., 2016; Fillmore, 2007; Oscar-Berman and Marinkovic, 2007; 
however, intoxicating doses of alcohol are associated with robust decrements in 
inhibitory control (Dougherty et al., 2008; Fillmore and Weafer, 2004; Loeber and Duka, 
2009), psychomotor performance (Harrison and Fillmore, 2005), attentional function 
(Marczinski and Fillmore, 2006), and working memory processes (Soderlund et al., 
2005; Weissenborn and Duka, 2000). Dose is a critical modulator of these effects, with 
subintoxicating BACs (i.e., ≤ ~0.065 g/dL) having less consistent effects on cognition 
and behavior. Evidence suggests, however, that these BACs can selectively disrupt 
critical neuropsychological processes, including sustained and/or divided attention, 
inhibitory control, and working memory (Boissoneault et al., 2014; Breitmeier et al., 
2007; de Wit et al., 2000; Friedman et al., 2011; Gilbertson et al., 2009; Holloway, 1994; 
Lloyd and Rogers, 1997; Jongen et al., 2016).  
 
There are numerous other factors besides dose that may modulate the effects of acute 
alcohol. Germane to this application, an individual’s family history (FH) of alcoholism 
may also affect their neurobehavioral response to a given dose. A substantial body of 


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literature indicates that FH positive (FH+) individuals have an altered profile of 
subjective responses to alcohol, with various conceptual models describing either 
consistently lower levels of response to alcohol challenge (i.e., the Low Level of 
Response [LLR] model), or increased stimulation on the ascending limb combined with 
decreased sedation on the descending limb (Morean and Corbin, 2010; Schuckit, 1994). 
Individuals’ expectations regarding the positive and negative effects of a given alcohol 
dose are also critical determinants of its neurobehavioral effects. Numerous studies 
indicate expectation of impairment is an important predictor of behavioral compromise 
following alcohol administration (Field et al., 2008; Fillmore et al., 1998; Marczinski and 
Fillmore, 2005).  
 
The neurophysiological and functional correlates of alcohol-induced neurobehavioral 
compromise have been explored using a number of imaging modalities, including PET 
(Volkow et al., 2006) and fMRI (Anderson et al., 2011; Marinkovic et al., 2012; 
Soderlund, et al., 2005). Taken together, these studies indicate acute alcohol- related 
disruption of functional activation and glucose utilization in brain areas related to 
affective, executive, and motor function, including anterior cingulate gyrus, prefrontal 
cortex, medial frontal cortex, and the basal ganglia. Notably, aberrant function of these 
areas and the evaluative, limbic, and executive networks they form have all been 
implicated as modulators of the experience of acute and chronic pain, suggesting a 
common neural framework underlying both the effects of alcohol and the pain 
experience (Hashmi et al., 2013). EEG/ERP studies, on the other hand, provide 
complementary evidence that even relatively low doses of alcohol disrupt the timing and 
magnitude of neurophysiological processes believed to reflect attentional and working 
memory processes (Bartholow et al., 2003; Kenemans et al., 2010; Lewis et al., 2013), 
which play an important role in the processing of nociceptive stimuli.  
 
In summary, although a substantial body of research addresses factors that modulate 
the consequences of acute alcohol consumption, work to date has almost exclusively 
been concerned with cognitive and behavioral impairment (Fillmore, 2007; Holloway, 
1994; Oscar-Berman and Marinkovic, 2007). Substantially less guidance is available 
regarding factors affecting analgesia resulting from alcohol use.  
 
Alcohol Analgesia. In the past 5 years, there has been increasing interest in interactions 
between alcohol use/misuse and chronic pain (Apkarian et al., 2013; Egli et al., 2012; 
Zale et al., 2015). Recent data suggest self-medication of pain with alcohol by patients 
with chronic pain is widespread (Brennan et al., 2005; Riley and King, 2009). 
Furthermore, new evidence suggests that that a pattern of low-to-moderate alcohol use 
is associated with less severe pain symptomatology in fibromyalgia patients 
(Boissoneault et al., 2016; Kim et al., 2013). However, few experimental investigations 
of alcohol analgesia have been conducted. Mullin and Luckhardt (1934) were 
responsible for the first report on alcohol analgesia in published literature, finding that 
doses equivalent to ~3-5 standard drinks reduced sensitivity to punctate pain (von Frey 
filament). Wolff and colleagues (1941, 1942), using a radiant heat paradigm, reported 
elevations of up to 45% in pain threshold at doses ranging from ~1-5 standard drinks, as 
well as a reduction in galvanic skin response associated with onset of the painful 


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stimulus. A subsequent study examining differential effects of a dose of alcohol 
intended to produce BACs ~0.09 g/dL in alcoholics and healthy controls found that 
analgesic effects in a cold pressor paradigm were significantly greater in alcoholics, 
indicating drinking history may play a role in determining the analgesic effects of acute 
alcohol administration (Cutter et al., 1976). As noted by Brown and Cutter (1977), 
however, these studies’ methodological limitations, including lack of placebo control, 
blinding, and accounting for sample characteristics (e.g., expectancies, age, drinking 
history, etc.), restrict their interpretability.  
 
Several subsequent studies expanded and improved on initial efforts by utilizing 
Widmark equations (Watson et al., 1981; Widmark, 1932) to better target specific BAC 
levels and by accounting for aspects of participants’ typical drinking pattern and history 
of alcoholism. Results of a double-blind, placebo controlled study using both 0.10 and 
0.05 g/dL doses among healthy college students suggested analgesic responses to 
pressure and cold pressor stimuli depended at least partially upon participants’ typical 
drinking pattern (Brown and Cutter, 1977). In a follow-up study, endorsement of alcohol 
use to increase confidence, reduce stress, and increase self-satisfaction was 
associated with analgesic effects following alcohol administration in nonalcoholic 
drinkers (Cutter et al., 1979). Importantly, these studies did not determine whether 
participants were at high familial risk for alcoholism, which is known to influence 
response to alcohol even in non-problem drinkers (Morean and Corbin, 2010). Stewart 
and colleagues (1995) found that, among non-alcoholic men, a legally intoxicating dose 
of alcohol (peak BAC ~0.09 g/dL) produced a reduction in pain ratings from electric 
shock, although this effect was significantly greater among those at high familial risk for 
alcoholism. In an attempt to minimize expectancy effects, several studies of alcohol 
analgesia using intravenous administration of alcohol vs. oral intake have been 
conducted. Although lacking ecological validity, these studies provide valuable insight 
into the pharmacological component of alcohol analgesia. James and colleagues (1978) 
found significant elevation in pressure pain thresholds over the course of infusion at 
both 1.5 g/kg and 0.75 g/kg. Similarly, BACs of 0.10 g/dL, but not 0.04 g/dL, produced a 
significant increase in pain tolerance in healthy drinkers (Perrino et al., 2008). 
Interestingly, this effect was not related to FH of alcoholism. A follow-up analysis by the 
same group revealed that a personality factor, neuroticism, interacted with FH such that 
those individuals with high neuroticism and a positive FH achieved a significantly 
greater analgesic response (i.e., reduction in pain intensity) at 0.04 g/dL than those who 
were FH negative or had low neuroticism, suggesting personality factors may interact 
with FH in determining analgesic responses to alcohol (Ralevski et al., 2010).  
 
Despite its potential importance, sex has not been systematically examined in studies of 
alcohol analgesia. Only one study to date has investigated sex as a moderator of 
alcohol effects, finding no significant effects (Perrino, et al., 2008). However, as noted 
by Horn-Hofmann et al. (2015), sex differences have been noted in the literature 
regarding alcohol-related expectancies and the neurobehavioral consequences of 
alcohol consumption. Furthermore, studies examining sex differences in the efficacy of 
opioid analgesics have identified greater reduction of pain sensitivity and relief from pain 
under opioids in women than men (Fillingim and Gear, 2004; Niesters et al., 2010). As 


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previously noted, alcohol acts directly and indirectly on most major neurotransmitter 
systems, including the endogenous opioid system (Vengeliene et al., 2008). Thus, it is 
plausible that the analgesic effects of alcohol may also be stronger among women.  
 
Summary. Self-administration of alcohol for pain relief is a common, yet risky (National 
Institute on Alcohol Abuse and Alcoholism, 2013) behavior among pain patients 
(Brennan, et al., 2005; Riley and King, 2009). Furthermore, alcohol use disorders are 
common among chronic pain patients and vice versa (Zale et al., 2015). Although the 
cognitive and behavioral effects of acute alcohol intake are relatively well- 
documented, significant gaps in understanding remain regarding alcohol 
analgesia. Critically, although FH of alcoholism is currently the best-studied 
modulator of alcohol analgesia (i.e., Perrino et al., 2008; Ralevski et al., 2010; 
Stewart et al., 1995), the relative contributions of sex, alcohol-related 
conditioning, and expectancies have not been studied. Furthermore, despite 
separate robust literatures regarding the neural correlates of acute alcohol intake and 
pain sensation, alterations in pain and reward- related networks associated with alcohol 
analgesia have never been characterized. In addition to providing an avenue for in vivo 
experimental evidence regarding theorized overlap between structures and networks 
associated with sensation and endogenous modulation of pain and alcohol intoxication 
(Apkarian et al., 2013; Egli et al, 2012), this project will drive the field forward by 
determining the relative contributions of the proposed mechanisms, allowing for a) 
targeted treatments to modifiable factors, including conditioning and expectancies; and 
b) further research on unmodifiable factors (i.e., sex) that may underlie self-medication 
of pain using alcohol. Healthy social drinkers provide an ideal population for initial 
investigations of alcohol analgesia due to their lack of complicating medical and 
psychosocial factors. Furthermore, understanding mechanisms underlying the analgesic 
effects of alcohol in healthy social drinkers who are currently pain-free is important 
given that these individuals may eventually develop acute and/or chronic pain and 
engage in self-medication behaviors. The investigative team’s combined experience in 
mechanistic and clinical studies regarding acute, chronic, and experimental pain; the 
neurobehavioral consequences of both acute and chronic alcohol use; and neuroimage 
acquisition and analysis ensures successful completion of the proposed work.  
 
5. Specific Aims: 
 
Aim 1. Test competing hypotheses regarding the effects of family history of 
alcoholism on alcohol analgesia. A substantial body of evidence suggests that 
individuals with FH of alcoholism (FH+) have differential subjective responses to acute 
alcohol administration compared to FH-, including greater pain reduction (Stewart et al., 
1995; Ralevski et al., 2010). Hypothesis (H)1. We hypothesize that alcohol 
administration will be associated with greater reduction in pain sensitivity in FH+ than 
FH- individuals. Based on our pilot data, we also predict H2. FH+ individuals will report 
lower subjective ratings of relief from pain after consuming alcohol. Confirmation would 
suggest FH+ individuals may self-administer greater quantities of alcohol to achieve 
pain relief, consistent with the Low Level of Response (LLR) model (Morean and 
Corbin, 2010). Disconfirmation would suggest the negative reinforcing effects of alcohol 


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may be especially pronounced in FH+ (i.e., sensitization). Previous studies suggest 
typical alcohol use, motivations to drink, and personality factors may influence alcohol 
analgesia, suggesting a critical role of conditioning and expectancies (Brown et al., 
1977; Cutter et al., 1979; Ralevski et al., 2010). On the basis of our pilot data, we 
predict H3. FH+ individuals will have stronger positive expectancies regarding alcohol 
analgesia, which will predict analgesic response to alcohol administration. Results also 
suggest H4. a conditioning effect such that individuals who endorse greater and more 
frequent alcohol consumption will experience a greater analgesic effect of alcohol.  
 
Aim 2. Imaging functional correlates of alcohol analgesia. Empirical data regarding 
neural correlates alcohol analgesia are needed to inform models proposing common 
substrates underlying pain and acute/chronic alcohol effects (e.g., Egli et al., 2012). 
Unlike other analgesics (e.g., mu-opioid agonists), alcohol acts on most major 
neurotransmitter systems. However, no studies have examined neural mechanisms 
underlying alcohol analgesia. Regions of interest (ROIs) include brain structures 
underpinning discriminative, affective, and cognitive components of the pain experience, 
including anterior/posterior cingulate cortices, thalamus, insula, somatosensory cortices, 
hypothalamus, amygdala, and medial/dorsolateral prefrontal cortex. These regions are 
also implicated in addiction (Egli et al., 2012) and are vulnerable to disruption following 
acute alcohol administration (e.g., Anderson et al., 2011; Marinkovic et al., 2012, 2013). 
Thus, we predict H5. that alcohol administration will be associated with disruption of 
BOLD activation and functional connectivity in/between regions associated with the 
affective and cognitive aspects of pain processing (e.g., insula, prefrontal cortices, 
amygdala, nucleus accumbens) during application of heat pain stimuli. Based on our 
pilot data, we expect H6. FH+ individuals will demonstrate more severe alcohol-related 
functional disruption in these ROIs, including motivation-related circuits implicated in 
transition to chronic pain (Baliki et al., 2011).  
 
Aim 3. Test sex as a moderator of alcohol and FH effects. On the basis of our pilot 
data, as well as studies of sex differences on the efficacy of opioid analgesics (Fillingim 
and Gear, 2004; Niesters et al., 2010), we expect H7. women will experience greater 
reductions in pain sensitivity as a result of alcohol consumption and report greater 
feelings of relief compared to men. We ask as Empirical Question 1. whether sex will 
serve as a moderator of the effect of FH of alcoholism on alcohol analgesia and its 
functional neural correlates. Evidence of sex by FH interactions may help to identify 
subgroups at particular risk for harm from self- medication of pain with alcohol.  
6. Research Plan: 
 
General Approach. For this study of healthy, community-dwelling moderating drinkers, 
we propose a repeated- measures, double-blind placebo-controlled factorial design with 
FH of alcoholism (+/-) and sex as between-subjects factors and alcohol administration 
(Alcohol Dose: placebo, 0.08 g/dL) as a within-subject factor. The study will include 
equal numbers of men and women. Study procedures will occur in the Center for Pain 
Research and Behavioral Health of the University of Florida under supervision of the PI 
(JB). The investigative team, including the PI; Drs. Robinson, Nixon, and Lai; and 
research assistants, will meet on a bi-weekly basis over the course of the project to 


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ensure successful completion. Recent progress regarding all aspects of the study will 
be addressed during these meetings, including ongoing review of recruitment practices 
and behavioral and imaging data quality. Drs. Robinson, Nixon, Lai, and Boissoneault 
will also work together to ensure all research assistants are fully trained to conduct the 
project.  
 
Methods  
 
Participants. Healthy volunteers (N=220; 110 women) will be recruited for the study via 
flyers, word of mouth, and internet and local radio advertisements with the aim of 
obtaining 110 completers; 55 women). Individuals aged 21-45 years will be recruited in 
order to avoid confounding effects of binge-drinking patterns associated with college-
aged individuals and the apparent increased susceptibility of older adults to the acute 
neurobehavioral effects of alcohol (e.g., Boissoneault et al., 2014). We plan to enroll a 
representative sample of participants from our recruitment area in north central Florida 
(i.e., 65% white, 23% black, 7% Asian, 5% other), including ~10% identifying as 
Hispanic or Latino (see targeted recruitment table).  
 
Selection Criteria. Participants will be excluded if they have a history of chronic pain 
(e.g., osteo- or rheumatoid arthritis, fibromyalgia, complex regional pain syndrome) or 
report regular (i.e., > weekly) use of analgesic medications; current major depression, or 
history of major depressive disorder if electroconvulsive therapy had been used; past 
diagnosis of any psychotic disorder; undercontrolled hypertension or diabetes (as 
reflected by self-report); neurological disease (e.g., multiple sclerosis, epilepsy, 
amyotrophic lateral sclerosis, Parkinson’s disease); serious medical illness (e.g, 
hepatitis, HIV/AIDS); impaired cognitive function; or history of drug or alcohol 
dependence. Because evidence suggests chronic smoking is associated with adverse 
changes in brain structure and neurobehavioral function (Boissoneault et al., 2011; 
Durazzo et al., 2013), participants must be non-smokers. Alcohol naïve individuals will 
also be excluded. To increase ecological validity and improve feasibility of recruitment, 
use of prescription and over-the-counter (OTC) medications will be allowed provided 
they do not contraindicate alcohol use (Boissoneault et al., 2014; Gilbertson et al., 
2009).  
 
Screening Procedure. Individuals will complete an initial screen upon contacting the 
Center for Pain Research and Behavioral Health via phone or email. During the initial 
screen, the PI or a trained research assistant will describe the study and general entry 
criteria. Individuals who qualify and remain interested will be scheduled for a formal 
screening in the laboratory. During this screening session, additional information 
regarding demographics, personal and FH of drug and alcohol use (including nicotine), 
affective and personality measures, attitudes about pain, alcohol-related expectancies, 
and medical history will be collected (see Table 1). Individuals reporting at least one 
parent with a history of alcohol problems on the FTQ will be considered to have a family 
history of alcoholism (FH+; Mann et al., 1985). Notably, in addition to measures of 
typical consumption, the Alcohol Use Questionnaire (AUQ) includes an assessment of 


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the maximum quantity of alcohol they have consumed in a single setting in the last 6 
months. Although not  
 exclusionary, this maximum 
quantity will be considered in 
exploratory analyses given 
evidence it may modulate 
the acute effects of alcohol 
on cognitive performance 
(Lewis and Nixon, 2013). 
Expectancy of pain relief 
from alcohol intake will be 
measured using item 11 of 
the Alcohol Expectancy 
Questionnaire (Brown, et al., 
1987) based on participants’ 
responses to the item, 
“Alcohol can act as an 
anesthetic for me; that is, it 
can deaden the pain”, 
expectancy will range from -
10 (strong disbelief that 
alcohol relieves pain) to 10 
(strong belief). We will also 
measure expectancy of pain 
relief from alcohol using the 
Expectancies for Alcohol 
Analgesia Inventory (Ditre 
et al., 2018) and a simple 
two item visual analog 
scale measure.  
 
All participants will be 
provided with a pamphlet 
containing information about local mental health services; if desired, the PI or research 
assistant will facilitate contact with clinical services. Any subjects endorsing suicidal or 
homicidal intent during screening will be withdrawn from the study. Dr. Robinson, who is 
a licensed clinical psychologist, will then provide appropriate referral.  
  
Participants who continue to qualify will be given a detailed description of the two 
laboratory sessions, the tasks and measures to be collected, and reasons for urine 
samples (drug and pregnancy testing). Baseline quantitative sensory testing (QST) 
measures of pain sensitivity and tolerance will be taken after participants’ eligibility is 
confirmed and they indicate their willingness to continue. Participants will provide their 
own transportation to screening sessions. Participants will be paid $15 for completing 
the screening phase of the study, which will require approximately 1-2 hours.  
 
Screening 
Measure  
Domain  
Exclusionary Cutoff  
BDI-II  
Depressive 
Symptomology  
≥ 20 (moderate 
depression)  
STAI  
State/Trait Anxiety  
Not Exclusionary  
AEQ  
Alcohol Expectancies  
Not Exclusionary  
AUQ  
Alcohol Use Pattern  
Not Exclusionary  
AUDIT  
Alcohol Use Disorder 
Sx 
≥ 8 
PILL 
Somatic preoccupation 
/neuroticism  
Not Exclusionary  
FTQ  
FH Assessment  
Not Exclusionary  
PSQI 
Sleep Quality 
Not Exclusionary 
BRS 
Resilience to stressors 
Not Exclusionary 
DIS 
Ability to tolerate 
physical discomfort 
Not Exclusionary 
EAA 
Expectancies regarding 
pain relief from alcohol 
Not Exclusionary 
PCS 
Pain catastrophizing 
Not Exclusionary 
PASS-20 
Pain-related Anxiety 
Not Exclusionary 
IRI 
Empathy 
Not Exclusionary 
Table 1. Screening Measures. BDI-II: Beck Depression Inventory (Beck et al., 1996); STAI: 
State-Trait Anxiety Inventory (Spielberger, 1983); AEQ: Alcohol Expectancies Questionnaire 
(Brown et al., 1987); AUQ: Alcohol Use Questionnaire (Cahalan et al., 1969); AUDIT: Alcohol 
Use Disorders Identification Test (Saunders et al., 1993); PILL: Pennebaker Inventory of 
Limbic Languidness; FTQ: Family Tree Questionnaire (Mann et al., 1985); PSQI: Pittsburgh 
Sleep Quality Index (Buysse et al., 1989). BRS: Brief Resilience Scale (Smith et al., 2008); 
DIS: Discomfort Intolerance Scale (Schmidt et al., 2006); EAA: Expectancies for Alcohol 
Analgesia Inventory (Ditre et al., 2018); PCS: Pain Catastrophizing Scale (Sullivan et al., 
1995); PASS-20: Pain Anxiety Symptoms Scale (Short Version; McCracken and Dhingra, 
2002); IRI: Interpersonal Reactivity Inventory (Davis, 1980). 


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Laboratory Sessions. Consistent with previous work (Boissoneault, et al., 2014; Lewis, et 
al., 2013), participants will be asked to fast for at least 4 hours prior to their scheduled 
session and abstain from consuming any alcohol in the 24 hours before laboratory 
sessions. Taking normal morning medications will be permitted, but no other OTC or 
prescribed medications (including allergy medications and analgesics) will be allowed on 
the day of testing. Following provision of a urine sample, a drug screening will be 
performed. 
This 
screen 
will 
test 
for 
tetrahydrocannabinol, 
cocaine, 
benzodiazepines, morphine, and methamphetamine (Innovacon, Inc., San Diego, 
CA). Participants testing positive for any of these drugs will be discontinued. A 
baseline breath alcohol concentration (BrAC) measure will be taken, which must 
be 0 g/dL. Women will complete a brief questionnaire regarding their menstrual cycle, 
including: 1) if they are currently menstruating or if they are post-menopausal; 2) the 
length of their menstrual cycle; 3) how many days have elapsed since their last menses 
began; 4) how long their menses typically lasts; and 5) if they use any hormonal 
preparations (e.g., birth control). Women of child bearing potential will also be given 
a pregnancy test; should a woman’s pregnancy test be positive, she will be 
excluded from the study with a recommendation to contact her physician. Women 
who are currently breastfeeding will also be excluded. All testing will be conducted in 
private rooms within the Center for Pain Research and Behavioral Health. Participants 
will be provided with a light breakfast one hour before alcohol administration (~200 kcal). 
Following breakfast, participants will repeat affective measures (BDI-II/STAI) as well as 
an Irritability Questionnaire (IRQ; Craig et al., 2008). Lunch will be provided following 
testing, as well as another light meal should a participant be retained in the Center during 
dinner hours while their BrAC levels drop. For laboratory sessions, the PI or a research 
assistant will schedule a ride with Uber or Lyft to drive participants home after the completion 
of the session. Research assistants will use the GPS features of the rideshare app to ensure 
that participants make it home safely. If the rideshare app indicates that the participant was 
dropped off somewhere other than the vicinity of their home, the attending researcher will call 
the number left by the participant and speak with the participant. If the participant does not 
answer the phone, the researcher will contact the IRB to report the protocol deviation. 
Participants will be paid $120 for completing each laboratory session (or $15/hour up to 
$120 for non-completers). Laboratory sessions will be separated by at least 48 hours.  
 
Alcohol Administration. Alcohol administration procedures are consistent with those 
used by Drs. Boissoneault and Nixon in their previous work, as well as NIAAA 
guidelines for the safe and ethical administration of alcohol in experimental settings 
(Brown et al., 2014). Participants will complete two laboratory sessions in which they will 
be administered one of two beverages: placebo (0.00 g/dL target BrAC) or active 
alcohol (0.08 g/dL target BrAC). Session order will be counterbalanced across 
participants. For laboratory sessions in which a participant will be given the active dose, 
the quantity of medical grade alcohol (100% or 95% ethanol) needed to achieve 0.08 
g/dL will be calculated using a modification of the Widmark formula. The medical 
(United States Pharmacoepia) grade ethanol used in this study will be obtained from 
standard laboratory supply providers (e.g., Fisher Scientific). The Widmark formula 


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utilizes age and weight measures for men and height and weight measures for women 
(Watson, et al., 1981; Widmark, 1932). Only research assistants over the age of 21 will 
be involved in drink mixing/administration procedures, and all research assistants will be 
trained by the PI in drink mixing/administration procedures. In order to maintain the 
study’s double blind, a researcher not involved in QST will be responsible for calculating 
alcohol doses and mixing drinks, and the dose calculation and mixing procedure 
confirmed by a second research assistant. Alcohol will be mixed with ice-cold sugar-free 
lemon-lime soda in a 1:3 ratio and split into two servings (Boissoneault, et al., 2014; 
Gilbertson, et al., 2009; Harrison et al., 2007). Placebo beverages will consist of only 
vehicle. Participants will consume both servings within 5 minutes, and both active and 
placebo drinks will be misted with alcohol to enhance placebo effectiveness. A small 
amount of alcohol will be placed on the rim of the glass and the surface of the drink in 
order to further mask the study condition. Participants will rinse their mouths thoroughly 
with water once their beverage has been consumed. To avoid influencing participants’ 
expectations regarding alcohol analgesia, no suggestion regarding the potential pain-
relieving effects of alcohol will be provided before or after beverage administration.  
 
BrAC/BAC Assessment. Blood alcohol concentration (BAC) will be estimated using two 
methods. Following beverage administration, breath alcohol concentration (BrAC) 
measures will be obtained every 10 minutes using standard a handheld breath analysis 
device (e.g., Intoxylizer 400PA, CMI, Inc., Owensboro, KY) until the participant is placed 
in the MRI device (i.e., 2 measurements). After this point, BAC will be approximated 
using salivary alcohol testing strips (QED Saliva Alcohol Test, OraSure Technologies, 
Inc. Bethlehem, PA), with collection occurring after each scan is completed (resulting in 
3 measurements occurring over the duration of scanning). Following scanning, breath 
measures will again be taken periodically until the participant’s BrAC is ≤ 0.02, 
consistent with NIAAA guidelines (Brown et al., 2014). They will then be transported 
home.  
 
Subjective Intoxication and Placebo Effectiveness. Participants will complete 10cm VAS 
measures of subjective intoxication (anchored from ‘not at all intoxicated’ to ‘most 
intoxicated imaginable’) (Harrison, et al., 2007). These assessments will be 
administered concurrently with each BrAC assessment, as well as immediately before 
and after QST assessments and functional image acquisitions. In order to assess the 
contribution of subjective stimulatory and depressant effects of alcohol to alcohol 
analgesia, the Subjective Effects of Alcohol Scale (SEAS; Morean et al., 2013) will also 
be administered immediately prior to QST assessments and the fMRI heat pain 
paradigm, providing measures of positive and negative aspects of stimulation and 
sedation (i.e., HIGH+/- and LOW+/-). At the conclusion of testing, participants will be 
asked whether they believe they received an alcoholic beverage; those who indicate 
they did not receive a beverage will be asked when they made that determination.  
 
QST Procedure. QST testing will occur in a private room within the Center for Pain 
Research and Behavioral Health during screening procedures and within the scanner 
suite during laboratory sessions. First, during screening, all subjects will undergo a set 
of calibration trials to establish individualized temperatures to be used during laboratory 


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sessions so that degree of analgesia achieved from beverage consumption can be 
assessed relative to a personalized baseline. These calibration trials will consist of an 
ascending series of thermal pulses starting at 43ºC and increasing by 1ºC until the 
participant’s tolerance is reached. After each pulse, participants will rate pain intensity 
using a visual analog scale (VAS). The lowest temperature with a VAS score of 5 will be 
used for thermal stimuli during laboratory sessions. Next, during both screening and 
laboratory sessions, we will employ a slowly ramping thermal stimulus (.5°C per second 
starting at 32°C) delivered to the glabrous skin of the foot. Pain ratings (using a 10 cm 
VAS ranging from “no pain” to “most intense pain imaginable”) will be collected every 5 
seconds during this process until the participant’s tolerance is reached in order to 
determine temperatures associated with pain threshold (i.e., temperature at which the 
stimulus first becomes painful) and tolerance (i.e., temperature at which the stimulus 
becomes unbearable). This protocol also allows for the examination of pain after-
sensation following removal of the thermal probe, a construct related to the clinical 
experience of chronic pain (Staud et al., 2007). To this end, participants will report 
current pain levels at 15 and 30 seconds following stimulus removal. VASs are 
considered the “gold standard” for laboratory and clinical pain assessment given that 
they have a ratio scale (Price et al., 1983) and are able to effectively separate the 
sensory (i.e., intensity) and affective (i.e., unpleasantness) components of the pain 
experience. The investigative team has extensive experience with these procedures, 
and is confident they can be completed safely and effectively. All thermal stimuli will be 
delivered using a computer-controlled Q-Sense fMRI Compatible thermal stimulator 
(Ramat Yishai, Israel), a Peltier-element based device. We propose to utilize a thermal 
stimulus paradigm because the processing of such stimuli is particularly well 
understood. Such paradigms have been demonstrated in the broader pain literature to 
be sensitive to group differences (e.g., chronic pain patients vs. healthy controls), as 
well as experimental manipulations like acute opioid analgesic treatment and placebo 
induction (e.g., Chung et al., 2007; Sevel et al., 2015; Staud et al., 2012). Furthermore, 
its use in this study will enhance comparability to previous work. Following each QST 
measure during laboratory sessions, participants will be provided with a 10 cm VAS 
assessing perceived relief from pain resulting from beverage consumption (anchored 
from “No relief at all” to “Most profound relief imaginable”). QST procedures will require 
approximately 10 minutes. During laboratory sessions, QST procedures will be 
administered prior to alcohol consumption to function as a point of reference for 
participants and again approximately 15 minutes after beverage consumption to allow 
for absorption of alcohol (Boissoneault et al., 2014).  
 
Neuroimaging Protocol. Neuroimaging data will be acquired using a research-dedicated, 
whole-body scanner within the McKnight Brain Institute. Using a standard 32-channel 
RF head coil, we will collect both structural and functional neuroimaging data. A high-
resolution, 3D structural scan will first be conducted using a T1- weighted MP-RAGE 
protocol. This T1-weighted structural image will predominately be used in pre-
processing all functional data. Although not a primary aim, assuming sufficient time in a 
scanning session, we will also collect magnetic resonance spectroscopy (MRS) data 
using a brief sequence (~3-4 minutes) so that brain neurotransmitter and ethanol levels 
can be measured in regions relevant to pain processing and alcohol intoxication. 


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Following these structural scans, functional imaging data acquisition will occur using two 
paradigms described below: 1) resting-state scanning, and 2) noxious thermal 
stimulation protocol. In total, participants will complete two resting-state scans and three 
task-based fMRI runs, amounting to a one-hour scanning session. Of particular 
importance is minimizing head motion during scanning when participants are 
intoxicated, as head motion has been shown to affect data quality (Goto et al., 2015). 
We will ensure that participants’ heads are heavily padded inside the head coil prior to 
scanning, and will use the Artifact Detection Tool to remove confounds of motion during 
pre-processing of data. Participants will be reminded of the importance of staying awake 
throughout the scanning process, and we will check in with participants between each 
scan to ensure they did not fall asleep. Dr. Lai will work with Dr. Boissoneault to 
continually monitor data quality throughout the project.  
 
Resting-State Scanning. First, participants will complete two resting-state (i.e., task-
free) scans while keeping their eyes open and focused on a fixation cross. Resting-state 
fMRI is a powerful tool used to elucidate large- scale neural networks underlying human 
brain architecture (Biswal et al., 2010). Of these intrinsic connectivity networks, the 
subcortical limbic network is most relevant to the current project. Although previous 
studies have examined this resting-state network in the context of heroin (Schmidt et al., 
2015) and tobacco (Janes et al., 2012) dependence, intrinsic connectivity of this 
network has yet to be explored in the context of acute alcohol effects. This project will 
use a resting-state fMRI protocol to examine differences in subcortical limbic system 
connectivity (as well as other pain- and reward-related resting state networks) between 
groups at baseline, as well as between conditions to determine whether acute alcohol 
consumption differentially disrupts this network in individuals with a family history of 
alcoholism. One resting state scan will use a conventional BOLD-sensitive T2* weighted 
sequence. The other will use a partial-continuous arterial spin labeling (pCASL) 
sequence because these scans yield estimates of cerebral blood flow (CBF) which can 
be used as covariates in BOLD analysis of subsequent task-based scans, accounting 
for the cerebrovascular effects of alcohol administration (Marinkovic et al., 2013). Each 
resting state scan will require approximately 9 minutes.  
 
fMRI Heat Pain Protocol. Three task-based fMRI runs will be conducted subsequent to 
resting-state scanning using a noxious thermal stimulation protocol. This protocol has 
been previously used in an NIH-funded study in which MER is a co-investigator 
(R01AT006334). For this task, a long MR-compatible thermal probe attached to a 
Medoc Q-Sense fMRI compatible thermal stimulator will be used to deliver noxious 
thermal stimuli. Blocks of thermal stimuli will be delivered to the glabrous skin of the foot 
at the individually calibrated temperature determined during the screening visit. 
Following each thermal stimulation block, participants will rate levels of pain intensity 
and perceived relief from alcohol. Each block will be preceded and/or followed by a 30-
second rest blocks. An electronic VAS will be presented following each thermal 
stimulation block for the purposes of rating pain intensity (anchored from “No pain at all” 
to “Most intense pain imaginable”). After each run, participants will rate their perceived 
degree of relief from pain as a result of consuming their beverage using an electronic 


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VAS anchored from “No relief at all” to “Most profound relief imaginable”. Runs will last 
for approximately 6 minutes, and will take place consecutively.  
 
Power Analysis. Power analysis and recruitment goals are based on results of our pilot 
study (see attached grant document for a detailed description of results). Power 
analyses were performed assuming two-tailed hypothesis tests. Effect sizes are 
reported as Cohen’s d, r, or f
2 (Cohen, 1988).  
Our pilot data suggested statistically large increases in pain threshold temperature (d = 
1.16) associated with BrACs ~.052 g/dL. Effects on pain tolerance temperature and 
intensity ratings were smaller (d = .28); however, our targeted sample of 110 completers 
will provide ~ 80% power these effects, and > 99% power to detect effects of alcohol on 
pain threshold.  
FH of alcoholism was associated with greater expectancy of pain relief from alcohol 
intake in our pilot work (d = 1.12), as well as lower ratings of pain relief (d = .54). Effects 
of sex on these measures were large (d > .88). Sex also appeared to be a potent 
moderator of alcohol analgesia (d > .90), with women showing stronger analgesic 
effects. Our sample will provide > 80% power to detect these effects. FH was 
associated with smaller effects on alcohol-related reductions in pain intensity (d = .42), 
as well as pain threshold and tolerance (d < .26), resulting in ~54% power to detect 
interactive effects of FH and dose on these measures.  
Across participants, preliminary data suggested small-to-moderate correlations between 
expectancy of pain relief from alcohol, ratings of pain relief, and typical daily drinking 
and reductions in pain sensitivity (.26 < r < .44). We anticipate ~80-99% power to detect 
these effects. However, our data also suggested that sex and FH may moderate these 
relationships. The interaction of sex and expectancy of pain relief strongly predicted 
increases in pain threshold and tolerance associated with alcohol intake (f
2 > 1.11). A 
similar effect was detected for the interaction of FH and expectancy of pain relief (f
2 > 
.81). A weaker interaction of FH and ratings of relief on QST measures was also 
detected (f
2 > .37). Likewise, interactions of sex with typical daily drinking and ratings of 
relief showed some relation to QST changes (f
2 < .21). We anticipate > 94% power to 
detect each of these interactions. There was little evidence of Sex or FH interactions 
with typical drinking on alcohol analgesia (f
2 < .04). Effect sizes of FH X Sex X 
expectancy/relief/typical drinking interactions could not be assessed given our limited 
sample; however, we anticipate sensitivity to detect an interactive f
2 > .14 with 80% 
power given our recruitment target.  
Data Analysis Strategy. Data will be analyzed using SPSS 24 (IBM Corp., Armonk, NY). 
 
Aim 1. Test competing hypotheses regarding the effects of family history of 
alcoholism on alcohol analgesia. To assess hypotheses related to Aim 1, FH status 
will be included as an independent variable in repeated measures general linear models 
analyses (rmGLM; SPSS GLM procedure; repeated: dose), with pain 
threshold/tolerance and intensity ratings, associated relief ratings, expectancy of pain 


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relief from alcohol, and SEAS measures (i.e., HIGH+, HIGH-, LOW+, and LOW-; 
Morean et al., 2013, 2015) as dependent variables. Demographic, personality/affective 
(i.e., BDI/STAI/IRQ/NEO-derived neuroticism), and biomedical (i.e., menstrual phase for 
female participants, sleep quality) variables will be included as covariates should any be 
found to correlate significantly with magnitude of alcohol analgesia or relief ratings. A 
main effect of FH status such that FH+ individuals have greater magnitude of alcohol 
analgesia (i.e., greater increases in pain threshold/tolerance and decreases in pain 
intensity ratings), more positive/fewer negative subjective alcohol effects, and stronger 
expectancy of pain relief from alcohol consumption will be interpreted as evidence in 
support of H1 and H3. Lower ratings of alcohol-related relief from pain in FH+ 
individuals will provide support for H2.  
 
To determine the independent contributions of expectancies and typical drinking 
behavior to alcohol analgesia, these measures will be included as independent 
variables in separate multiple regression analyses including interaction vectors with sex 
and FH, with magnitude of alcohol analgesia (e.g., increased pain threshold or reduction 
in pain intensity ratings) as the dependent variable. They will then be entered into 
simultaneous regression analysis to assess independence of their effects. A positive 
association between typical drinking and analgesic response to alcohol will provide 
support for H4. Risk of Type I error will be mitigated through the use of Tukey’s HSD. 
Although not a primary aim, the relationship between individuals’ rate of rise of BAC 
following alcohol consumption and magnitude of alcohol analgesia will be examined in 
exploratory analyses. For FH+ participants, potential effects of the sex of affected 
parents and concordance with the participants’ sex (i.e., sex-matched vs. unmatched 
pairs) will also be assessed.  
 
Aim 2. Imaging functional correlates of alcohol analgesia and its modulating 
factors.  
H5, that alcohol administration will be associated with disruption of BOLD activation 
in/between regions associated with affective and cognitive aspects of pain processing 
during application of heat pain stimuli, and H6, that this disruption will be stronger 
among FH+ individuals, especially within motivation-related structures/circuits, will be 
evaluated using a two-part process. For all analyses described, motion will be controlled 
for at the individual subject level (i.e., first level) by including all six movement 
parameters (x/y/z translation, pitch/roll/yaw) and outlier volumes (determined using the 
Artifact Reduction Toolbox) as nuisance covariates. We will also co-vary for mean 
cerebral blood flow measured using pCASL-based resting state scans. Familywise error 
will be controlled for all analyses using false discovery rate correction (FDR; Benjamini 
and Hochberg, 1995) at p < .05.  
 
Resting-state analyses: Pre-processed resting-state data will be analyzed using hybrid 
ICA-seed-based fcMRI analyses (Kelly et al., 2010). For this approach, independent 
components analysis (ICA) and seed- based correlations are used in tandem. First, ICA 
will be used to empirically derive a priori regions of interest (ROIs) based on resting-
state networks identified from the study’s participants. Networks of particular interest in 
this study include those associated with processing of nociceptive stimuli and those that 


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are disrupted in chronic pain, including default mode network (DMN), salience network 
(SN), executive control network (ECN), and subcortical limbic network (LN) (Martucci 
and Mackey, 2016). ICA will be conducted using the voxel-to- voxel processing stream 
in the CONN toolbox, which involves back-projection of ICs identified across subject 
and condition to identify spatial components, followed by back-projection of these 
components to individual subjects (Calhoun et al., 2001). ICs most closely matching 
networks of interest will be identified based on masks derived from NeuroSynth (Yarkoni 
et al., 2011). Second, seed-based fcMRI analyses will examine Fishers’ r-to-z 
transformed correlations between the ICA-derived seed ROIs and all other voxels in the 
brain. Seed-based correlation analyses will be conducted in the Conn Toolbox 
(Whitfield-Gabrieli & Nieto-Castanon, 2012). Hybrid ICA-seed-based fcMRI has been 
shown to yield accurate and reproducible results (Franco et al., 2013; Kelly et al., 2010). 
We will examine interactions of group and condition on connectivity of these resting- 
state networks using repeated measures GLM, followed by simple main effects 
decomposition. 
  
Task-based analyses: Alcohol-related changes in BOLD activity in pain- and reward-
related brain structures during painful stimulation will be evaluated using a GLM-based 
approach in SPM12. Following convolution of the canonical hemodynamic response 
function with the heat stimulation paradigm at the single subject level, group-level 
effects of dose, sex, and FH on pain-related activations in ROIs and in whole brain will 
be assessed. To examine the changes in functional connectivity associated with alcohol 
analgesia, task-based data will be analyzed using the psychophysiological interaction 
(PPI) pipeline within the Conn Toolbox. PPI is a method of examining task-modulated 
increases in functional connectivity through GLM by yielding an interaction term (i.e., 
PPI regressor) from the product of a task’s convolved time course (e.g., blocks of 
noxious thermal stimulation) and the time course from a seed ROI (O’Reilly et al., 
2012). Relevant seed ROIs for this analysis will be generated using ICA as described 
above. We will examine task-dependent functional connectivity in pain- and reward-
related networks, both between groups and within conditions, using rmGLM.  
 
Aim 3. Test sex as a moderator of alcohol and FH effects.  
To evaluate Aim 3, sex will be included as a factor of interest in rmGLM analyses 
described under Aims 1 and 2. A sex by dose interaction such that alcohol consumption 
produces greater reductions in pain sensitivity and higher VAS ratings of relief for 
women than men will provide support for H7. Presence or absence of a significant sex 
by family history by dose interactions on metrics of alcohol analgesia will inform 
Empirical Question 1. Sex will also be included as a factor of interest in analyses of 
functional neuroimaging data to determine whether sex and FH of alcoholism interact to 
determine the effects of acute alcohol administration on pain-related brain processes.  
 
7.    Possible Discomforts and Risks: 
 
Psychological Discomforts and Risks. Some aspects of the questionnaires utilized in 
this proposal may make study participants uncomfortable, especially those dealing with 
affect or medical history. To ameliorate this possibility, participants will be informed they 


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can withdraw from the study at any time or skip individual questions that may be 
upsetting to them.  
 
Acute Alcohol Intake. Alcohol intake may result in dizziness, nausea, and vomiting 
should a participant tolerate the active dose of alcohol poorly. The risk of these as well 
as more serious consequences may increase if a participant uses medications that 
contraindicate the use of alcohol (e.g. benzodiazepines/opioid analgesics). Should a 
participant experience any of these symptoms, they will be allowed to rest until 
symptoms subside and will be allowed to withdrawal from the study if desired. We have 
attempted to minimize this risk by recruiting only those who are regular moderate 
drinkers and excluding those regularly taking prescription medications that 
contraindicate the use of alcohol. Ss will be rescheduled if they report having taken 
prescription or over-the-counter medications that contraindicate alcohol use on the day 
of testing.  
 
Pregnancy: Alcohol intake is an unacceptable risk in pregnancy. Therefore, anyone of 
childbearing potential will be tested for pregnancy on the morning of the laboratory 
session. Positive pregnancy tests will result in exclusion from study and lab staff will 
assist in making a referral as appropriate. Finally, any documents associated with a 
participant testing positive for pregnancy will be destroyed without reference to a 
specific cause.  
 
Breath Analyzer Testing: Breath analyzer testing may result in dizziness or 
lightheadedness for some individuals. However, the PI has administered many of these 
tests and never observed a significant negative consequence. Staff will be trained to 
recognize discomfort resulting from breath analyzer testing and will assist participants in 
ameliorating symptoms should they occur (eg., discontinue testing, place head between 
knees, etc.).  
 
MRI Scanner. The MRI scanner generates a very powerful magnetic field. To avoid all 
potential harm to participants as a result of exposure to this field, we will follow all UF 
CTSI Human Imaging Core screening procedures. By following the Human Imaging 
Core checklist, we will ensure no participants have metal of any kind implanted in their 
body, have any pacing devices (i.e., heart pacemaker), metal in their eyes, or certain 
types of heart valves or brain aneurysm clips. Some participants may also feel anxious 
about the confined space in the MRI. To attenuate this possibility, participants will be 
reassured that they can communicate with researchers and MRI staff through a speaker 
system. They will also be given the option to stop the experiment at any time during 
scanning. Finally, the MRI system produces very loud noises, which – in very rare cases 
– can produce hearing loss. To reduce this risk, participants are required to use both 
earplugs and headphones.  
 
QST Discomfort and Risks. QST, by definition, will induce thermal pain in participants. 
However, risk of harm as a result of QST procedures is minimal for the following 
reasons: 1) the pain is transient in nature and generally subsides immediately after the 
procedure; 2) participants are instructed that they may stop any procedure at any time 


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with no adverse consequences; 3) the level of pain experienced by participants is below 
their tolerance level; and 4) although pain sensation may continue after thermode 
removal (at discretion of the participant), this is not expected to last longer than 90 
seconds. Furthermore, because QST instrumentation cannot produce thermal stimuli 
above 52ºC and is equipped with an automatic shutdown system (preventing prolonged 
delivery of high-intensity stimuli) the risk of burning the skin is very slight. Of over 800 
participants tested with QST procedures in the Center for Pain Research and 
Behavioral Health over several studies, less than 1.5% have suffered a first-degree 
burn, less than 0.5% have suffered a second-degree burn, and none have suffered a 
third-degree burn. Should a participant suffer a burn following thermal QST or continued 
pain 24 hours after pressure pain QST, an adverse event will be reported to the IRB.  
 
Participant Confidentiality Risks. The investigative team places a high priority on 
protection of patient confidentiality and will use the following procedures to protect 
patients. Unique participant identifiers will be generated in order to collect protected 
health information (i.e., from questionnaires) for research purposes. Paper 
questionnaires and forms will be stored in a locked storage space, digital information 
will be stored in encrypted, password protected files on secure servers, and the data 
that links the participants to their unique identifiers will be stored in a separate location. 
When the study is completed and all raw data is entered electronically, participant 
identifiers will be destroyed. Despite these efforts, it is possible that participant 
confidentiality may be breached. If a breach occurs, it will be reported to NIH and the 
IRB and appropriate measures will be taken. These measures include but are not 
limited to informing affected participants of the breach and assisting with protective 
measures once the breach is detected.  
 
Data and Safety Monitoring Plan  
Because the proposed study does not comprise a clinical trial, a formal Data and Safety 
Monitoring Board has not been planned. The investigative team, including Drs. 
Boissoneault, Nixon, Robinson, and Lai, will meet quarterly to discuss data and safety 
monitoring issues. Any issues identified during the course of these meetings will be 
handled in a manner consistent with the University of Florida’s policies.  
 
8.    Possible Benefits: There are no potential benefits to participants in this study. 
 
9.    Conflict of Interest: There is no conflict of interest involved with this study beyond 
the professional benefit from academic publication or presentation of the results. 
 
10.   References: 
 
Anderson, B. M., Stevens, M. C., Meda, S. A., Jordan, K., Calhoun, V. D., & Pearlson, 
G. D. (2011). Functional imaging of cognitive control during acute alcohol intoxication. 
Alcohol Clin Exp Res, 35, 156-165.  
Apkarian, A. V., Bushnell, M. C., Treede, R. D., & Zubieta, J. K. (2005). Human brain 


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mechanisms of pain perception and regulation in health and disease. Eur J Pain, 9, 
463-484.  
Apkarian, A. V., Neugebauer, V., Koob, G., Edwards, S., Levine, J. D., Ferrari, L., Egli, 
M., & Regunathan, S. (2013). Neural mechanisms of pain and alcohol dependence. 
Pharmacol Biochem Behav.  
Bartholow, B. D., Pearson, M., Sher, K. J., Wieman, L. C., Fabiani, M., & Gratton, G. 
(2003). Effects of alcohol consumption and alcohol susceptibility on cognition: a 
psychophysiological examination. Biol Psychol, 64, 167-190.  
Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Beck Depression Inventory, Second 
Edition. San Antonio: The Psychological Corporation.  
Benjamini, Y., & Hochberg, Y. (1995). Controlling the False Discovery Rate - a Practical 
and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society 
Series B-Methodological, 57(1), 289-300.  
Biswal, B. B., Mennes, M., Zuo, X. N., Gohel, S., Kelly, C., Smith, S. M., Beckmann, C. 
F., Adelstein, J. S., Buckner, R. L., Colcombe, S., Dogonowski, A. M., Ernst, M., Fair, 
D., Hampson, M., Hoptman, M. J., Hyde, J. S., Kiviniemi, V. J., Kotter, R., Li, S. J., Lin, 
C. P., Lowe, M. J., Mackay, C., Madden, D. J., Madsen, K. H., Margulies, D. S., 
Mayberg, H. S., McMahon, K., Monk, C. S., Mostofsky, S. H., Nagel, B. J., Pekar, J. J., 
Peltier, S. J., Petersen, S. E., Riedl, V., Rombouts, S. A., Rypma, B., Schlaggar, B. L., 
Schmidt, S., Seidler, R. D., Siegle, G. J., Sorg, C., Teng, G. J., Veijola, J., Villringer, A., 
Walter, M., Wang, L., Weng, X. C., Whitfield-Gabrieli, S., Williamson, P., 
Windischberger, C., Zang, Y. F., Zhang, H. Y., Castellanos, F. X., & Milham, M. P. 
(2010). Toward discovery science of human brain function. Proc Natl Acad Sci U S A, 
107, 4734-4739.  
Boissoneault, J., Gilbertson, R., Prather, R., & Nixon, S. J. (2011). Contrasting 
behavioral effects of acute nicotine and chronic smoking in detoxified alcoholics. Addict 
Behav, 36, 1344-1348.  
Boissoneault, J., Sklar, A. L., Prather, R., & Nixon, S. J. (2014). Acute effects of 
moderate alcohol on psychomotor, set shifting, and working memory function in older 
and younger social drinkers. Journal of Studies on Alcohol and Drugs, 75.  
Boissoneault, J., Letzen, J., Lai, S., O'Shea, A., Craggs, J., Robinson, M., & Staud, R. 
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IRB Project #: 201800992
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INFORMED CONSENT FORM
to Participate in Research, and
AUTHORIZATION 
to Collect, Use, and Disclose Protected 
Health Information (PHI)
INTRODUCTION
Name of person seeking your consent:
Place of employment & position: 
Please read this form which describes the study in some detail. A member of the research 
team will describe this study to you and answer all of your questions. Your participation is 
entirely voluntary. If you choose to participate you can change your mind at any time and 
withdraw from the study. You will not be penalized in any way or lose any benefits to which 
you would otherwise be entitled if you choose not to participate in this study or to withdraw.
We aim to create an environment of mutually respectful interactions between research staff 
and participants. We pledge that research staff will not engage in disrespectful behavior or 
use racist, sexist, or other inappropriate language, and ask the same of you. If you have 
questions about your rights as a research subject or have concerns regarding the conduct 
of our research staff during your participation, please call the University of Florida 
Institutional Review Board (IRB) office at (352) 273-9600.   
GENERAL INFORMATION ABOUT THIS STUDY
1.
Name of Participant ("Study Subject")
___________________________________________________________________ 
2.
What is the Title of this research study?
Characterizing Alcohol Analgesia
Study ID:IRB201800992   Date Approved: 4/5/2023


IRB Project #: 201800992
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3.
Who do you call if you have questions about this research study?
Michael Robinson, PhD, Principal Investigator (352-273-6617)
Sara Nixon, PhD, Co-Investigator (352-294-4900)
Song Lai, PhD, Co-Investigator (352-294-5597)
4.  Who is paying for this research study? 
The sponsor of this study is the National Institute on Alcohol Abuse and Alcoholism 
(NIAAA).
5.  In general, what do you need to know about this Research Study?
Agreeing to become involved in any research is always voluntary.  By signing this 
form, you are not waiving any of your legal rights. If you decide not to participate in 
this research, you will not be penalized in any way and you will not lose any benefits 
to which you are entitled. If you have questions about your rights as a research 
subject, please call the University of Florida Institutional Review Board (IRB) office at 
(352) 273-9600.    
You are being asked to be in this research study because you are a healthy social 
drinker between the ages of 21 to 45. You should not be in this study if you:

Have a medical history or condition that would conflict with study participation, 
including chronic pain 

Are unable to speak and read English

Are currently participating in another research study that could interfere or 
influence the outcomes of this study

Are unable to provide informed consent

Have impaired mental function

Have a history or presence of psychiatric, psychological, or neurological 
disorder(s)

Have not consumed alcohol in the past

Have a serious medical illness (e.g., hepatitis, HIV/AIDS)

Have a history of drug or alcohol dependence

Smoke cigarettes or use other tobacco/nicotine products

Are pregnant or breastfeeding
a) In general, what is the purpose of the research, how long will you be 
involved?  
The purpose of this research study is to improve understanding of how alcohol use 
affects pain and sensory function. This study has 3 total sessions. Your screening 
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visit will take approximately 1 to 2 hours, and the laboratory sessions will require 4 
to 8 hours each.
b) What is involved with your participation, and what are the procedures to be 
followed in the research? 
Participating in this study involves 3 different visits to our laboratory, including this 
screening session. During screening, you will complete a number of 
questionnaires and undergo thermal/sensory pain testing. During the following two 
laboratory sessions, you will consume a beverage that may or may not contain 
alcohol and undergo thermal/sensory pain testing and MRI scanning. We provide 
transportation to and from laboratory sessions. See Item #7 below for additional 
details.
c) What are the likely risks or discomforts to you? 
Briefly, potential risks involved with participating in this study include alcohol 
intoxication, minor redness or swelling from the thermal probe, discomfort from the 
MRI noise, and potential uneasiness from the enclosed space in the MRI. Other 
potential risks and discomforts, including COVID-19 transmission, are described in 
detail in Item #10 below.
d) What are the likely benefits to you or to others from the research? 
There is no direct benefit to you for participating in this study. However, society-at-
large and the medical community may benefit by enhancing our understanding of 
how alcohol affects pain sensation and sensory function.
e) What are the appropriate alternative procedures or courses of treatment, if 
any, that might be helpful to you?  
Participating in this study is entirely optional. This is not a treatment study. If you 
are a faculty/staff member or student at the University of Florida, your decision 
whether to participate will have no impact on your employment or academic 
status.
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 CAN YOU EXPECT IF YOU PARTICIPATE IN THIS STUDY?
6.   What will be done as part of your normal clinical care (even if you did not 
participate in this research study)? 
Your normal clinical care will not be affected by participation in this study.
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7.  What will be done only because you are in this research study? 
The initial screening visit will include the following procedures:
a) After arriving at the Center for Pain Research and Behavioral Health (located 
on the ground floor of the UF Dental Tower in room DG-64), the Informed 
Consent form will be reviewed with you to make certain that you understand 
everything that is involved in the study procedures. 
b) You will complete several questionnaires about your demographics (age, 
education, etc.), family history of drug and alcohol use (including nicotine), 
typical drinking behavior, affect and personality, alcohol-related expectancies, 
and medical history.
c) You will undergo thermal sensory/pain testing using a testing machine 
commonly used in clinical settings. This device has a small square piece that is 
used to apply heat to the skin. The amount of heat is controlled by a computer 
and will be applied to the bottom of your foot. You will be asked to rate the 
intensity of your pain experience. Although uncomfortable and/or painful, the 
amount of heat applied to your skin will not be sufficient to cause a burn. You 
can discontinue the procedures at any time so that you do not experience pain 
you find intolerable. 
Visits 2 and 3 are laboratory sessions:
a) Laboratory sessions will occur in our laboratory (DG-64) and the McKnight 
Brain Institute at the University of Florida. You will be asked to fast for at least 
4 hours prior to your scheduled session and abstain from alcohol consumption 
24 hours before each session. You may take your normal morning 
medications, but you should not take any OTC medications (including allergy 
medications and analgesics) the morning before your session. If you are not 
able to meet these requirements, please let us know so your laboratory 
session can be rescheduled.
b) We will provide transportation to and from the laboratory sessions.
c) You will be screened via urine analysis for illicit drug use, including marijuana, 
cocaine, benzodiazepines, morphine, and methamphetamine. 
d) You will also be initially screened for your breath alcohol concentration, which 
must be negative upon your arrival to the laboratory. If results of this test or the 
urine drug screen are positive, you will be discontinued, or your session will be 
rescheduled at the PI’s discretion.
e) If you are of childbearing potential, you will be given a pregnancy test. If the 
test is positive, the results will be destroyed, and you will be discontinued from 
the study.
f)
You may undergo repeated thermal stimulation testing in our laboratory (DG-
64). Thermal stimulation testing will be done before beverage consumption, 15 
minutes after beverage consumption, and after MRI scans. 
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g) You will be provided with breakfast and a light lunch.
h) You will complete paper/pencil mood assessments of your mood. 
i)
You will be given your beverage, which will consist of alcohol (if any) mixed 
with sugar-free lemon-lime soda. Once finished, you will be asked to rinse your 
mouth thoroughly with water.
j)
You will then be asked to complete assessments regarding your intoxication 
level and periodically breathe into a breathalyzer.
k) You will complete structural and functional MRI scans of your brain. Functional 
MRI scans will involve thermal stimulation testing.
l)
After testing is completed and your breath alcohol concentration is at or below 
0.02 g/dL, you will be transported home via Uber or Lyft. If the GPS feature of 
the rideshare app indicates that you were dropped off somewhere other than 
the vicinity of your home, the attending researcher will call to check in with you.
If you experience a physical or mental emergency during your screening or laboratory 
session, we will request emergency services by dialing 911. 
Once this research study is completed, any information that could identify you might 
be removed from any identifiable private information or identifiable biospecimens 
collected and that, after such removal, the information or biospecimens could be 
used for future research studies or distributed to another investigator for future 
research studies without additional informed consent from you or your legally 
authorized representative. 
If you have any questions now or at any time during the study, please contact one of 
the research team members listed in question 3 of this form.
8.
How long will you be in this research study?
This study has 3 total sessions. Your screening visit will take approximately 1 to 2 
hours, and the laboratory sessions will require 4 to 8 hours each.
9.
How many people are expected to take part in this research study?
Up to 220 people may participate in this study. We plan for at least 110 people to 
complete the study. 
10. What are the possible discomforts and risks from taking part in this research 
study?
This study might involve the following risks and discomforts to you:
WHAT ARE THE RISKS AND BENEFITS OF THIS STUDY AND 
WHAT ARE YOUR OPTIONS?
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
You may feel intoxicated after consuming the alcohol dose used in this study. 
Alcohol consumption may result in nausea and/or vomiting, as well as 
drowsiness, impaired memory and concentration, and decreased inhibitions. 
This may result in impairment to your normal function. However, the alcohol 
effects will have worn off by the end of the treatment day and assurance will be 
made that you are not intoxicated before you are transported home from the 
laboratory.

There are minimal risks associated with the thermal stimulation protocol. This 
includes minor redness that goes away within a few minutes to hours. Burns 
are very rare, and you may stop the testing procedure at any time without 
penalty. The heat testing procedure may be uncomfortable or unpleasant. 
However, if the pain is greater than you wish to tolerate, you can discontinue to 
the procedures at any time.

This study uses MRI. MRI is a procedure that allows researchers to look inside 
your body using a scanner that sends out a strong magnetic field and radio 
waves. The risks of MRI are:
o
The MRI scanner contains a very strong magnet. Therefore, you should 
not have the MRI if you have certain types of metal implanted in your 
body. For example, any pacing device (like a heart pacer), any metal in 
your eyes, or certain kinds of heart valves or brain aneurysm clips.
o
There is not much room inside the MRI scanner. You may be 
uncomfortable if you do not like to be in enclosed spaces 
(“claustrophobia”).
o
The MRI scanner produces loud noises, which have produced hearing 
loss in a very small number of patients. You will be given earplugs to 
reduce this risk.
o
If you are of childbearing potential, there may be unknown risks to the 
fetus. Therefore, you will be given a pregnancy test before each MRI 
scan.
o
MRI performed for research purposes only may not be reviewed with 
the same scrutiny as would be done for your specific health care needs.

Certain medications may have harmful interactions with alcohol. For this 
reason, you will not be allowed to participate in the study if you use 
prescription medications that cause drowsiness (for example, benzodiazepines 
or opioids for pain). 

You may feel uncomfortable answering questions about private topics during 
screening and laboratory sessions. However, you may choose not to answer 
any questions that make you feel uncomfortable. You will not be allowed to 
participate in the study if you use prescription medications that cause 
drowsiness (for example, benzodiazepines or opioids for pain). 

You may experience dizziness or lightheadedness from breathalyzer testing.
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
There is a risk of spreading or contracting COVID-19 during participation in this 
study.  We take the following steps to limit spread of COVID-19:
o
Research personnel will wear a disposable Level 1 surgical mask 
during all interactions with you or other personnel during screening 
visits. Screening visits do not involve use of a breathalyzer device. 
During laboratory visits, which do involve breathalyzer use and thus 
production of aerosols, research staff will wear a KN95 mask. If you do 
not have a mask, you will be met at the door upon arrival for each 
session and provided a disposable Level 1 surgical mask that you are 
required to wear for the duration of all sessions, except when 
otherwise instructed (for example, while drinking a beverage or 
providing a breath sample).

If you are not willing to wear a mask, we ask that you do not 
participate in this study.
o
All screening material documents will be presented to you at the 
beginning of each study session. You will be instructed when to flip to 
the next page to reduce the number of times forms are passed 
between people. Writing utensils will be designated for participants 
and disinfected between study sessions.
o
All study equipment will be sanitized before and after each use. Study 
equipment includes but is not limited to: tabletops, door knobs, thermal 
stimulator for QST procedures, laptops, and breathalyzers for 
measuring breath alcohol concentrations. While in the MRI suites, we 
will follow guidelines for safety provided by the AMRIS facility.
We will take appropriate steps to protect any information collected about you. 
However, there is a slight risk that information about you could be revealed 
inappropriately or accidentally. Depending on the nature of the information, such a 
release could upset or embarrass you, or possibly affect your insurability or 
employability.
Questions 17-21 in this form discuss what information about you will be collected, 
used, protected, and shared.
This study may include risks that are unknown at this time.
Participation in more than one research study or project may further increase the risks 
to you.  If you are already enrolled in another research study, please inform one of the 
research team members listed in question 3 of this form or the person reviewing this 
consent with you before enrolling in this or any other research study or project.
Throughout the study, the researchers will notify you of new information that may 
become available and might affect your decision to remain in the study. 
If you wish to discuss the information above or any discomforts you may experience, 
please ask questions now or call one of the research team members listed in question 
3 in this form.
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11a. What are the potential benefits to you for taking part in this research study?
There is no direct benefit to you for participating in this study.
11b. How could others possibly benefit from this study?
Society-at-large and the medical community may benefit by enhancing our 
understanding of how alcohol affects pain sensation and sensory function.
11c. How could the researchers benefit from this study?
In general, presenting research results helps the career of a scientist. Therefore, the 
Principal Investigator listed in question 3 of this form may benefit if the results of this 
study are presented at scientific meetings or in scientific journals.
12. What other choices do you have if you do not want to be in this study? 
Participation in this study is entirely optional. This is not a treatment study.
13a. Can you withdraw from this study?
You are free to withdraw your consent and to stop participating in this study at any 
time.  If you do withdraw your consent, you will not be penalized in any way and you 
will not lose any benefits to which you are entitled. If you decide to stop participation 
after you have consumed a beverage containing alcohol, we ask that you remain in 
the laboratory until your breath alcohol concentration is ≤ .02 g/dL for safety reasons.  
If you decide to withdraw your consent to participate in this study for any reason, 
please contact one of the research team members listed in question 3 of this form.  
They will tell you how to stop your participation safely.
If you have any questions regarding your rights as a research subject, please call the 
Institutional Review Board (IRB) office at (352) 273-9600.
13b.If you withdraw, can information about you still be used and/or collected?
If you choose to withdraw from the study, no new information will be collected. The 
information already collected could still be used to complete the study.
13c. Can the Principal Investigator withdraw you from this study? 
You may be withdrawn from the study without your consent for the following reasons:

The study is cancelled and/or discontinued, or other administrative reasons.

You have an adverse reaction to the alcohol dose or pain sensitivity testing.

You have recently used medications or drugs that are not allowed, or you are 
pregnant or breastfeeding

You have not followed pre-test instructions.
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WHAT ARE THE FINANCIAL ISSUES IF YOU PARTICIPATE?
14. If you choose to take part in this research study, will it cost you anything?
There will be no cost to you for participating in this research study.
15. Will you be paid for taking part in this study?
Yes. You will receive a $15 gift card for completing the screening session. You will 
also receive a $120 gift card for each laboratory session. The total amount you will be 
paid for completing all study procedures is $255. You will receive partial payment if 
you do not complete all study procedures.
Your payment for participation in this research study is handled through the University 
of Florida’s Human Subject Payment (HSP) Program. Your information, which will 
include your name, address, and date of birth, is protected. Access to the (HSP) 
Program site is limited to certain staff with the assigned security role. You will be 
randomly assigned a specific identification (ID) number to protect your identity.  The 
study team will provide you with an informational form called the Prepaid Card Facts 
document. If you have any problems regarding your payment call the HSP Office 
(352) 392-9057. 
If you are paid more than $75 for taking part in this study, your name and social 
security number will be reported to the appropriate University employees for purposes 
of making and recording the payment as required by law. You are responsible for 
paying income taxes on any payments provided by the study. Payments to 
nonresident aliens must be processed through the University of Florida Payroll and 
Tax Services department. If the payments total $600 or more in a calendar year, the 
University must report the amount you received to the Internal Revenue Service 
(IRS). The IRS is not provided with the study name or its purpose. If you have 
questions about the collection and use of your Social Security Number, please visit: 
http://privacy.ufl.edu/SSNPrivacy.html. 
16. What if you are injured because of the study?  
If you are injured as a direct result of your participation in this study, only the 
professional services that you receive from any University of Florida Health Science 
Center healthcare provider will be provided without charge. These healthcare 
providers include physicians, physician assistants, nurse practitioners, dentists or 
psychologists. Any other expenses, including Shands hospital expenses, will be billed 
to you or your insurance provider. 
You will be responsible for any deductible, co-insurance, or co-payments. Some 
insurance companies may not cover costs associated with research studies or 
research-related injuries. Please contact your insurance company for additional 
information. 
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The Principal Investigator will determine whether your injury is related to your 
participation in this study. 
No additional compensation is routinely offered. The Principal Investigator and others 
involved in this study may be University of Florida employees. 
As employees of the University, they are protected under state law, which limits 
financial recovery for negligence.
Please contact one of the research team members listed in question 3 of this form if 
you experience an injury or have questions about any discomforts that you 
experience while participating in this study.
17. How will your health information be collected, used and shared?
If you agree to participate in this study, the Principal Investigator will create, collect, 
and use private information about you and your health. This information is called 
protected health information or PHI. In order to do this, the Principal Investigator 
needs your authorization. The following section describes what PHI will be collected, 
used and shared, how it will be collected, used, and shared, who will collect, use or 
share it, who will have access to it, how it will be secured, and what your rights are to 
revoke this authorization. 
Your protected health information may be collected, used, and shared with others to 
determine if you can participate in the study, and then as part of your participation in 
the study. This information will be gathered only through your self-report, participation 
in study procedures, or from your study visits or telephone calls. More specifically, the 
following information may be collected, used, and shared with others: 
a) Your name, research record number, contact information, and dates associated 
with tests related to your participation.  
b) Social security number (for payment purposes)
c) Date/time of negative drug and pregnancy tests (results of positive tests are 
destroyed) 
d) Demographic and health status information  
e) Responses to questionnaires  
f)
Results of laboratory tests
g) Results of MRI scans
This information will be stored in locked filing cabinets or on computer servers with 
secure passwords or encrypted electronic storage devices. 
Some of the information collected could be included in a "limited data set" to be used 
for other research purposes. If so, the limited data set will only include information that 
does not directly identify you. For example, the limited data set cannot include your 
name, address, telephone number, social security number, photographs, or other 
codes that link you to the information in the limited data set. If limited data sets are 
created and used, agreements between the parties creating and receiving the limited 
data set are required in order to protect your identity and confidentiality and privacy.
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18. For what study-related purposes will your protected health information be 
collected, used, and shared with others?
Your PHI may be collected, used, and shared with others to make sure you can 
participate in the research, through your participation in the research, and to evaluate 
the results of the research study. More specifically, your PHI may be collected, used, 
and shared with others to help improve understanding of mechanisms underlying the 
effects of alcohol on pain and sensory function.
Once this information is collected, it becomes part of the research record for this 
study.  
19. Who will be allowed to collect, use, and share your protected health 
information?
Only certain people have the legal right to collect, use and share your research 
records, and they will protect the privacy and security of these records to the extent 
the law allows. These people include:

the study Principal Investigator (listed in question 3 of this form) and research 
staff associated with this project.

other professionals at the University of Florida or Shands Hospital that provide 
study-related treatment or procedures.

the University of Florida Institutional Review Board (IRB; an IRB is a group of 
people who are responsible for looking after the rights and welfare of people 
taking part in research).  
20. Once collected or used, who may your protected health information be shared 
with?
Your PHI may be shared with:

Research staff at the University of Florida associated with this project.

The study sponsor (listed in Question 4 of this form).

United States governmental agencies who are responsible for overseeing 
research, such as the Food and Drug Administration, the Department of Health 
and Human Services, and the Office of Human Research Protections.
To help us protect your privacy, we have been granted a Certificate of Confidentiality 
from the National Institutes of Health. With this Certificate, the researchers cannot be 
forced to disclose information that may identify you, even by a court subpoena, in any 
federal, state, or local civil, criminal, administrative, legislative, or other proceedings. 
The researchers will use the Certificate to resist any demands for information that 
would identify you, except as explained below.
The Certificate cannot be used to resist a demand for information from personnel of 
the United States Government that is used for auditing or evaluation of federally 
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funded projects or for information that must be disclosed in order to meet the 
requirements of the federal Food and Drug Administration (FDA).
You have been informed that a Certificate of Confidentiality does not prevent you from 
voluntarily releasing information about yourself or your involvement in this research. If 
an insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers may not use the Certificate to withhold that 
information. That is, if you give written consent for the release of information, we 
cannot withhold that information and we cannot hold responsibility for how that person 
may use your information. 
The Certificate of Confidentiality does not prevent the researchers from disclosing 
voluntarily, without your consent, information that would identify you as a participant in 
the research project under the following circumstances. If we learn about child abuse, 
elder abuse, or intent to harm yourself or others, we will report that information to 
appropriate authorities.
It is possible that once this information is shared with authorized persons, it could be 
shared by the persons or agencies who receive it and it would no longer be protected 
by the federal medical privacy law.  
21. If you agree to take part in this research study, how long will your protected 
health information be used and shared with others?
Your PHI will be used and shared with others until the end of the study.
You are not required to sign this consent and authorization or allow researchers to 
collect, use and share your PHI. Your refusal to sign will not affect your treatment, 
payment, enrollment, or eligibility for any benefits outside this research study. 
However, you cannot participate in this research unless you allow the collection, use 
and sharing of your protected health information by signing this consent and 
authorization.
You have the right to review and copy your protected health information.  However, 
we can make this available only after the study is finished.
You can revoke your authorization at any time before, during, or after your 
participation in this study. If you revoke it, no new information will be collected about 
you. However, information that was already collected may still be used and shared 
with others if the researchers have relied on it to complete the research. You can 
revoke your authorization by giving a written request with your signature on it to the 
Principal Investigator.
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SIGNATURES
As an investigator or the investigator’s representative, I have explained to the participant 
the purpose, the procedures, the possible benefits, and the risks of this research study; 
the alternative to being in the study; and how the participant’s protected health 
information will be collected, used, and shared with others: 
Signature of Person Obtaining Consent and Authorization
Date
You have been informed about this study’s purpose, procedures, possible benefits, and 
risks; the alternatives to being in the study; and how your protected health information will 
be collected, used and shared with others. You have received a copy of this Form. You 
have been given the opportunity to ask questions before you sign, and you have been told 
that you can ask questions at any time.  
You voluntarily agree to participate in this study. You hereby authorize the collection, use 
and sharing of your protected health information as described in sections 17-21 above. By 
signing this form, you are not waiving any of your legal rights.
Signature of Person Consenting and Authorizing
Date
 
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