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Background: Several studies have objectively quantified drinking through the use of Alcohol Monitoring System's (AMS) transdermal alcohol concentration (TAC) device known as SCRAM CAM. Criteria that AMS uses to detect drinking are known to be conservative and only reliably detect heavy drinking equivalent to 5 or more standard drinks. Our group has developed Research Rules used to process TAC data in a manner that will detect low-level and moderate drinking even though it is below the AMS criteria for detection., Methods: Sixteen male and 14 female paid research volunteers wore TAC monitors for 28 days in their natural environments and responded daily to text message prompts to self-report the previous day's drinking. Current analyses describe the Research Rules that we developed and how use of those rules impacts the detection of self-reported drinking treated as the standard in sensitivity/specificity analysis., Results: We observed 606 occurrences of positive TAC events over a total of 867 days and processed the TAC data to retain 345 as possible drinking events, even though AMS criteria confirmed drinking for only 163 of these events. The kinds of TAC events removed or retained by our rules are illustrated as cases of low and moderate drinking days that were detected by our rules but not by the conservative AMS criteria. AMS-confirmed TAC events have a high specificity (99.8%) to detect primarily heavy drinking, but have a poor sensitivity to detect lower-level drinking and a poor specificity as an indicator of alcohol abstinence. In contrast, our Research Rules detected 100% of TAC events detected by AMS but also detected 31% of the lower-level drinking events not detected by AMS, with 91% specificity., Conclusions: Reliance upon the AMS criteria for alcohol detection affords a high specificity for detection of heavy drinking but is a poor indicator of abstinence rates. In contrast, use of our Research Rules provides more sensitive means to quantify either any drinking or low-moderate levels of drinking while still maintaining good specificity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to characterize the pharmacokinetics of the phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated human blood samples taken from 18 participants in a clinical laboratory setting after consumption of 2 standard doses of ethanol (EtOH)., Methods: Male and female participants received either 0.4 or 0.8 g/kg oral doses of EtOH during a 15-minute period. Blood samples were collected before and throughout 6 hours immediately after alcohol administration and then again at days 2, 4, 7, 11, and 14 of the follow-up period. PEth 16:0/20:4 levels were quantified by high-performance liquid chromatography with tandem mass spectrometry detection., Results: (i) The increase in PEth 16:0/20:4 from baseline to maximum concentration was less than that of PEth 16:0/18:1 or PEth 16:0/18:2 homologs during the 6-hour period after EtOH administration; (ii) the mean half-life of PEth 16:0/20:4 was 2.1 ± 3 (SD) days, which was shorter than the mean half-life of either PEth 16:0/18:1 or PEth 16:0/18:2, 7.6 ± 3 (SD) or 6.8 ± 4 (SD) days, respectively., Conclusions: The pharmacokinetics of PEth 16:0/20:4 in whole blood samples is detectable after alcohol consumption and differs in amount synthesized and rate of elimination versus PEth 16:0/18:1 and 16:0/18:2. Measuring the concentrations of these 3 homologs has the potential to provide more information about the amount and time frame of alcohol consumption than any one alone., (© 2018 by the Research Society on Alcoholism.)

Alcohol consumption is typically assessed via self-report methods, though there are concerns over the accuracy of this information. Transdermal alcohol monitoring can passively and continuously measure alcohol consumption with minimal interference in daily life. The current study examines the correspondence between daily self-reported alcohol consumption and transdermal alcohol monitors. Thirty-two healthy men (n = 16) and women (n = 16) wore a transdermal alcohol monitor for 28 days. Participants were instructed to drink as they usually do and prompted daily with a survey link to report yesterday's drinking. Data analyses focused on the following comparisons: (1) the overall correspondence between self-reported drinking and TAC readings; (2) the sensitivity of various TAC criteria thresholds to detect self-reported drinking (TAC thresholds of none, low, moderate, and heavy); and (3) the risks of false positive TAC findings using self-reported drinking as the Gold Standard. Participants self-reported drinking a total of 324 days, of which, TAC events were detected on 212 days (65.4%). When participants self-reported not drinking (399 days), zero TAC was also found on 366 days (92%). The correspondence between self-reported drinking and transdermal concentrations tended to be good: overall, when self-reported drinking was reported, TAC also detected drinking 65.4% of the time., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers., Methods: A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in 15 minutes. Blood and breath samples were collected before, at various times up to 360 minutes postconsumption, and 2, 4, 7, 11, and 14 days after alcohol consumption. Initial rates of PEth synthesis, 360 minutes area under the PEth pharmacokinetic curves (AUCs), and elimination half-lives were determined., Results: (i) Nonzero PEth levels were observed before alcohol dosing for most participants, despite 7 days of alcohol use monitoring; (ii) 0.4 and 0.8 g/kg doses of alcohol produced proportional increases in PEth levels in all but 1 participant; (iii) the initial rate of synthesis of both PEth homologues did not differ between the 2 doses, but was greater for PEth 16:0/18:2 than PEth 16:0/18:1 at both doses; (iv) the mean AUC of both PEth homologues was higher at 0.8 g/kg than at 0.4 g/kg; (v) the mean AUC of 16:0/18:2 was greater than that of PEth 16:0/18:1 at both alcohol doses; (vi) the mean half-life of PEth 16:0/18:1 was longer than that of PEth 16:0/18:2 (7.8 ± 3.3 [SD] days and 6.4 ± 5.0 [SD] days, respectively); and (vii) there were no sex differences in PEth 16:0/18:1 or 16:0/18:2 pharmacokinetics., Conclusions: The results of this study support the use of PEth 16:0/18:1 and 16:0/18:2 as biomarkers for alcohol consumption. Because of consistent pharmacokinetic differences, the levels of these 2 PEth homologues may provide more information regarding the quantity and recentness of alcohol consumption than either alone., (Copyright © 2018 by the Research Society on Alcoholism.)

Background: Several studies demonstrate the utility of Alcohol Monitoring Systems' (AMS) transdermal alcohol concentration (TAC) monitor to objectively quantify drinking. AMS standard criteria (i.e., TAC >0.02 g/dl) used for drinking detection are deliberately conservative, but consequently only detect drinking equivalent to 5 or more standard drinks. Our study sought to characterize the sensitivity of TAC measurement to detect low-level drinking defined as the consumption of 1 to 3 beers., Methods: Data were pooled from 3 studies giving controlled doses of 1, 2, 3, 4, and 5 Corona© beers (12 oz = 0.92 standard units) to 32 male and 29 female research volunteers wearing TAC monitors under controlled conditions. Analyses describe the sensitivity to detect drinking at various peak TAC thresholds beginning with any positive reading >0 g/dl, and then using TAC thresholds of 0.02 and 0.03 g/dl., Results: Nearly 40% of participants drinking 1 beer did not have a positive TAC reading. However, positive TAC readings were observed in more than 95 and in 100% of participants drinking 2 and 3 or more beers, respectively. The probability of peak TAC detection was a positive function of the number of beers consumed and a negative function of the minimum TAC threshold for detection. Drinking was somewhat more likely to be detected in females than males drinking 2 to 5 beers, but not after 1 beer. Use of AMS standard criteria only reliably detected the consumption of 5 beers, and 45.9% of all occasions of drinking 1 to 3 beers were undetected using 0.02 g/dl as a threshold., Conclusions: Peak TAC levels between 0 and 0.02 g/dl must be considered to detect the low-level drinking of 1 to 3 standard drinks, and such thresholds are necessary when researchers and clinicians want to detect low-level drinking., (Copyright © 2015 by the Research Society on Alcoholism.)

Background: Recently, we demonstrated that transdermal alcohol monitors could be used in a contingency management procedure to reduce problematic drinking; the frequency of self-reported heavy/moderate drinking days decreased and days of no to low drinking increased. These effects persisted for three months after intervention. In the current report, we used the transdermal alcohol concentration (TAC) data collected prior to and during the contingency management procedure to provide a detailed characterization of objectively measured alcohol use., Methods: Drinkers (n=80) who frequently engaged in risky drinking behaviors were recruited and participated in three study phases: a 4-week Observation phase where participants drank as usual; a 12-week Contingency Management phase where participants received $50 each week when TAC did not exceed 0.03g/dl; and a 3-month Follow-up phase where self-reported alcohol consumption was monitored. Transdermal monitors were worn during the first two phases, where each week they recived $105 for visiting the clinic and wearing the monitor. Outcomes focused on using TAC data to objectively characterize drinking and were used to classify drinking levels as either no, low, moderate, or heavy drinking as a function of weeks and day of week., Results: Compared to the Observation phase, TAC data indicated that episodes of heavy drinking days during the Contingency Management phase were reduced and episodes of no drinking and low to moderate drinking increased., Conclusions: These results lend further support for linking transdermal alcohol monitoring with contingency management interventions. Collectively, studies to date indicate that interventions like these may be useful for both abstinence and moderation-based programs., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Rationale: Previously, we reported methods to estimate peak breath alcohol concentrations (BrAC) from transdermal alcohol concentrations (TAC) under conditions where alcohol consumption was controlled to produce similar BrAC levels in both sexes., Objective: This study characterized differences in the relationship between BrAC and TAC as a function of sex and developed a model to predict peak BrAC that accounts for known sex differences in peak BrAC., Methods: TAC and BrAC were monitored during the consumption of a varying number of beers on different days. Both men (n=11) and women (n=10) consumed one, two, three, four, and five beers at the same rate in a 2-h period. Sex and sex-related variables were considered for inclusion in a multilevel model to develop an equation to estimate peak BrAC levels from TAC., Results: While peak BrAC levels were significantly higher in women than men, sex differences were not significant in observed TAC levels. This lack of correspondence was evidenced by significant sex differences in the relationship between peak TAC and peak BrAC. The best model to estimate peak BrAC accounted for sex-related differences by including peak TAC, time-to-peak TAC, and sex. This model was further validated using previously collected data., Conclusions: The relationship between peak TAC and actual peak BrAC differs between men and women, and these differences can be accounted for in a statistical model to better estimate peak BrAC. Further studies are required to extend these estimates of peak BrAC to the outpatient environment where naturalistic drinking occurs.

Background: Research on contingency management to treat excessive alcohol use is limited due to feasibility issues with monitoring adherence. This study examined the effectiveness of using transdermal alcohol monitoring as a continuous measure of alcohol use to implement financial contingencies to reduce heavy drinking., Methods: Twenty-six male and female drinkers (from 21 to 39 years old) were recruited from the community. Participants were randomly assigned to one of the two treatment sequences. Sequence 1 received 4 weeks of no financial contingency (i.e., $0) drinking followed by 4 weeks each of $25 and then $50 contingency management; Sequence 2 received 4 weeks of $25 contingency management followed by 4 weeks each of no contingency (i.e., $0) and then $50 contingency management. During the $25 and $50 contingency management conditions, participants were paid each week when the Secure Continuous Remote Alcohol Monitor (SCRAM-II™) identified no heavy drinking days., Results: Participants in both contingency management conditions had fewer drinking episodes and reduced frequencies of heavy drinking compared to the $0 condition. Participants randomized to Sequence 2 (receiving $25 contingency before the $0 condition) exhibited less frequent drinking and less heavy drinking in the $0 condition compared to participants from Sequence 1., Conclusions: Transdermal alcohol monitoring can be used to implement contingency management programs to reduce excessive alcohol consumption., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Transdermal alcohol sensors continuously collect reliable and valid data on alcohol consumption in vivo over the course of hours to weeks. Transdermal alcohol readings are highly correlated with breath alcohol measurements, but transdermal alcohol levels lag behind breath alcohol levels by one or more hours owing to the longer time required for alcohol to be expelled through perspiration. By providing objective information about alcohol consumption, transdermal alcohol sensors can validate self-report and provide important information not previously available. In this article, we describe the development and evaluation of currently available transdermal alcohol sensors, present the strengths and limitations of the technology, and give examples of recent research using the sensors., (Copyright © 2012 by the Research Society on Alcoholism.)

Binge drinking is a public health concern due to its association with negative health outcomes as well as increased legal and social consequences. Previous studies have frequently used self-reported alcohol consumption to classify binge drinking episodes; however, these measures are often limited in both detail and accuracy. Some researchers have begun using additional measures such as blood (BAC) and breath (BrAC) alcohol concentrations to supplement self-report data. Transdermal alcohol testing, or the detection of alcohol expiration through the skin, offers advantages over BAC and BrAC measures by allowing for continuous and noninvasive monitoring of an individual's drinking behavior in real time. Despite these advantages, this technology has not been widely used or studied outside of forensic applications. The present research compares transdermal alcohol concentration (TAC) and BrAC readings during the consumption of alcohol ranging from moderate drinking to binge drinking in 22 adult regular drinkers in order to investigate the sensitivity and specificity of the TAC monitors. We observed that BrAC and TAC measures were broadly consistent. Additionally, we were able to develop an equation that could predict BrAC results using TAC data, indicating TAC data would be an appropriate substitute in research and clinical contexts where BrAC readings are typically used. Finally, we were able to determine a cutoff point for peak TAC data that could reliably predict whether a participant had engaged in moderate or more-than-moderate drinking, suggesting TAC monitors could be used in settings where moderate or reduced drinking is the goal.

Background: Acute alcohol administration affects impulsive behavior, although these effects vary as a function of alcohol dose, assessment instrument, and time of measurement following administration., Methods: We concurrently examined the dose-dependent effects of alcohol on three distinct types of impulsivity tasks (continuous performance [IMT], stop-signal [GoStop], and delay-discounting [SKIP] tasks). Ninety healthy alcohol drinkers were assigned to one of the three task groups (n=30 each), each group experienced placebo, 0.2, 0.4, 0.6, and 0.8 g/kg alcohol doses across 5 experimental days, and task performance was assessed at 0.5h before and 0.25, 1.0, and 2.0 h after alcohol administration. We hypothesized that impulsive responding on all tasks would be increased by acute alcohol administration both across time and during the peak BrAC, but the magnitude would depend on the task being tested. Analyses included the time course and the peak BrAC effects. Task comparisons of peak behavioral changes following each dose are illustrated using standardized scores., Results: While alcohol consumption increased impulsive responding during all three tasks to some extent, our hypothesis was only partially supported. During the IMT, the 0.6 and 0.8 g/kg doses produced increased impulsive responding across time and at the peak BrAC. However, during the GoStop and SKIP, impulsivity increased across time regardless of the alcohol dose size, with no differences in impulsive responding among dose conditions at peak BrAC., Conclusions: This study demonstrated alcohol-induced changes in impulsivity are not uniformly affected by alcohol. These data, in conjunction with previous studies, further support that impulsivity is not a unitary construct.

Background: Alcohol produces biphasic effects of both stimulation and sedation. Sensitivity to these effects may increase the risk for the development of alcoholism. Alcohol-induced changes in stimulation and sedation are commonly assessed with self-report questionnaires in human research and with physical activity monitoring in animal research. However, little is known about the effects of alcohol on physical activity or the relationship between physical activity and subjective self-report measures of stimulation and sedation following alcohol consumption in humans., Methods: Thirty healthy men and women (n = 15 each) from 21 to 38 years old completed daily measurements of physical activity and self-reports of stimulation and sedation following alcohol or placebo consumption. Across each of the four experimental days, all participants consumed a placebo, 0.4, 0.6, or 0.8 g/kg dose of 95% alcohol in a counterbalanced order. Breath alcohol concentrations, physical activity levels, and self-reported stimulation and sedation were measured at baseline and on the ascending and descending limbs of the breath alcohol concentration (BrAC) curve., Results: All alcohol doses increased physical activity, but these increases were time- and dose-dependent. Increases in physical activity lasted across both ascending and descending limbs of the BrAC curve. Following the 0.6 g/kg dose, both physical activity and self-reported stimulation increased during the ascending BrAC. Separate analyses of self-reported sedation scores indicated that alcohol consumption also increased sedation for the 0.6 and 0.8 g/kg doses. Physical activity was not significantly correlated with either self-reported stimulation or sedation at any time point., Conclusions: These findings suggest that assessments of subjectively measured stimulation and sedation and objectively measured physical activity each assess unique aspects of the effects of alcohol. Used simultaneously, these measures may be useful for examining underlying mechanisms of the effects of alcohol on behavior.

Rationale: Indirect evidence supports a link between serotonergic activity and individual differences in the behavioral response to alcohol, but few studies have experimentally demonstrated that an individual's biological state can influence the sensitivity to alcohol-induced behaviors., Objective: Our purpose was to temporarily modify serotonin synthesis in healthy individuals to determine how altered biological states may interact with alcohol administration to affect impulsive behavior., Materials and Methods: In a repeated-measures design, 18 normal controls consumed a 50-g L: -tryptophan (Trp) depleting (ATD) or loading (ATL) amino-acid beverage that temporarily decreased or increased (respectively) serotonin synthesis before receiving either a moderate dose of alcohol (0.65 g/kg) or placebo. All participants completed three impulsivity testing sessions on each of the five experimental days. Session one was a baseline session. Session two included testing after ATD-only or ATL-only. Session three included: (1) placebo after ATL (ATL+PBO); (2) placebo after ATD (ATD+PBO); (3) alcohol after ATL (ATL+ALC); (4) alcohol after ATD (ATD+ALC); and (5) Alcohol-only conditions. Impulsivity was assessed using the Immediate Memory Task (Dougherty et al., Behav Res Methods Instrum Comput 34:391-398, 2002), a continuous performance test yielding commission errors that have been previously validated as a component of impulsive behavior., Results: Primary findings were that ATD-only increased impulsive responding compared to ATL-only, and ATD+ALC increased commission errors to levels higher than either the ATL+ALC or Alcohol-only conditions., Conclusions: These findings demonstrate that reduced serotonin synthesis can produce increased impulsivity even among non-impulsive normal controls, and that the behavioral effects of alcohol are, in part, dependent on this biological state.

Monitors of transdermal alcohol concentration (TAC) provide an objective measurement of alcohol consumption that is less invasive than measurements in blood, breath or urine; however, there is a substantial time delay in the onset of TAC compared to blood or breath alcohol concentrations (BrACs). The current study examined the characteristics of the delay between peak TAC and peak BrAC.~Aims~Objective~Data was aggregated from three experimental laboratory studies (N = 61; 32 men, 29 women) in which participants wore a TAC monitor and BrAC was monitored while drinking one, two, three, four and five beers in the laboratory. Analyses examined the sex- and dose-related differences in peak BrAC and TAC, the time-to-peak BrAC and TAC, and time lag between the peak BrAC and TAC values.~Methods~Methods~The times-to-peak were an increasing function of the number of beers consumed. At each level of beer consumption the peak TAC averaged lower than peak BrAC and times-to-peak TAC were longer than for BrAC. The time-to-peak BrAC and TAC was longer for women than men. The congruence between peak TAC and BrAC increased as a function of the beers consumed. No sex difference in the time lag between peak BrAC and TAC was detected.~Results~Results~The congruence between TAC and BrAC and time lags between TAC and BrAC are related to the number of beers consumed. Peak values of TAC and BrAC became more congruent with higher doses but the time lag increased as a function of the amount of alcohol consumed.~Conclusions~Conclusions~The time delay (or lag) and congruence between transdermal vs. BrACs increases as the number of beers increases. Though sex differences are evident in peak transdermal and BrACs, no sex differences were evident in the time lag and the congruence between transdermal and breath alcohol concentrations.~Short Summary~Objective [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to characterize the pharmacokinetics of 2 homologues of phosphatidylethanol ( PEth) and their combined total in uncoagulated, whole blood samples taken from participants in a human clinical laboratory study after consumption of low doses of ethanol (EtOH). Methods As part of a larger study, 14 male and 13 female participants received either 0.25 or 0.50 g/kg oral doses of EtOH during a 15-minute period. Blood samples were collected before and throughout 6 hours after each EtOH dose on the day of consumption and then every 3 days during the next 14 days. PEth 16:0/18:1 and PEth 16:0/18:2 levels were quantified in blood samples by HPLC/ MS/ MS and reported separately or as their combined total (combined PEth). Breath alcohol concentrations (Br ACs) were measured concurrently with each blood collection. Transdermal alcohol concentrations were measured every 30 minutes during the entire 22-day study to confirm the absence of drinking during a 7-day period before and the 14-day period after EtOH consumption. Results (i) Single doses of 0.25 and 0.50 g EtOH/kg produced proportional increases in Br AC and combined PEth levels of all participants; (ii) the areas under the curve ( AUCs) for each participant's Br AC levels during the 6-hour period after EtOH administration were correlated with AUCs of cPEth (calculated as the AUC of the increase above baseline for combined PEth); (iii) the mean half-life of combined PEth, determined during the 14-day period after EtOH consumption, was 4.6 ± 3.5 ( SD) days (range: 1.0 to 13.1 days). Conclusions Combined PEth is a sensitive biomarker for the identification of relatively low levels of EtOH consumption. The measurement of these 2 homologues may provide additional sensitivity to identify low levels of drinking. [ABSTRACT FROM AUTHOR]

Background Transdermal alcohol monitoring is a noninvasive method that continuously gathers transdermal alcohol concentrations ( TAC) in real time; thus, its use is becoming increasingly more common in alcohol research. In previous studies, we developed models that use TAC data to estimate peak breath alcohol concentration (Br AC) and standard units consumed when the rate of consumption was tightly controlled. Methods Twenty-two healthy participants aged 21 to 52 who reported consuming alcohol on 1 to 4 days per week were recruited from the community. The final study sample included 11 men and 8 women. Both TAC and Br AC were monitored while each participant drank 1, 2, 3, 4, and 5 beers in the laboratory on 5 separate days. In contrast to previous studies, a self-paced alcohol administration procedure was used. Results While there was considerable variation in the times it took to consume each beer, key TAC parameters were not affected by pace of drinking. TAC data were then used in combination with the previously derived equations and estimated peak Br AC and standard units of alcohol consumed. Conclusions Transdermal alcohol monitoring can be used to reliably estimate peak Br AC and standard number of units consumed regardless of the rate of consumption, further demonstrating its usefulness in clinical research. [ABSTRACT FROM AUTHOR]