Differences in Next-Day Adverse Effects and Impact on Mood of an Evening of Heavy Alcohol Consumption between Hangover-Sensitive Drinkers and Hangover-Resistant Drinkers

The combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero, are collectively referred to as the alcohol hangover. Previous research revealed that 10 to 20% of drinkers claim not to experience next-day hangovers. Past studies were usually limited to single timepoint assessments. The aim of the current semi-naturalistic study was to compare the next-day effects of an evening of alcohol consumption of self-reported hangover-resistant drinkers (n = 14) with those of a group of self-reported hangover-sensitive drinkers (n = 15) at hourly timepoint throughout the day (09:30 until 15:30). Assessments of 23 hangover symptoms, mood (Profiles of Mood States-Short Form), and daytime sleepiness (Karolinska Sleepiness Scale) were made hourly after both an alcohol day and an alcohol-free control day. Additional morning assessments were made for mood (State-Trait Anxiety Inventory-Y, Beck’s Depression Inventory-II), risk-taking behavior (RT-18), past night sleep (Groningen Sleep Quality Scale), alcohol consumption, and activities during the test days. No significant differences were found regarding the amount of alcohol consumed and the total sleep time of the two groups. The hangover-sensitive group reported having a hangover as well as the presence of a variety of hangover-related symptoms, which were most severe in the morning and then gradually decreased during the day. The most frequently reported and most severe symptoms were sleepiness and fatigue, concentration problems, and headache. In contrast, the hangover-resistant group reported the absence of a hangover and the presence and severity of next-day symptoms did not significantly differ from the control day, except for increased fatigue and reduced vigor. The next-day effects on sleepiness-related complaints and vigor were significantly more pronounced among hangover-sensitive drinkers compared to hangover-resistant drinkers. In conclusion, contrary to hangover-resistant drinkers, hangover-sensitive drinkers report a variety of hangover symptoms that gradually ease during the day, but are still present in the afternoon.


Introduction
The alcohol hangover refers to the combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero [1]. Among the most frequently reported adverse effects are being tired, sleepiness, concentration problems, and headache [2][3][4]. There is increasing research into the pathology of alcohol hangovers [5][6][7]. Current theories suggest that the alcohol hangover comprises an inflammatory response to Participants were included in the study if they had Dutch nationality, were between 18 and 30 years old, and consumed alcohol. Participants had to be healthy (i.e., no physical or mental disease), non-smoking, and not using illicit or medicinal drugs (except contraception). Health status was verified by the study physician, and sex, age, weight, and height were recorded. At screening, and on each test day, the absence of illicit drug use (including amphetamines (including 3,4-Methylenedioxymethamphetamine, MDMA), barbiturates, cannabinoids, benzodiazepines, cocaine, and opiates) was verified via a urine drug screen (AlfaScientic Designs Inc., Poway, CA, USA) and female participants completed a urine β-human chorionic gonadotropin (HCG) pregnancy test. None of the participants tested positive on these tests. A breath alcohol test was performed using an Alcotest 7410 Breath Alcoholmeter (Dräger, Hoogvliet, The Netherlands) to verify the absence of alcohol consumption on the control day and possible residual alcohol on the alcohol day. On the test days, participants were not allowed to take any treatments to prevent or relieve hangover symptoms or medicinal drugs that may potentially reduce hangover symptoms such as painkillers (e.g., acetaminophen or aspirin).
At screening, potential participants were thoroughly interviewed about their drinking behaviors and history of presence or absence of alcohol hangovers. The purpose of the study was to compare hangover-resistant drinkers with hangover-sensitive drinkers. Therefore, participants were included that reported consuming considerable amounts of alcohol on a regular drinking occasion. Although recent research revealed that hangovers can occur after consuming any amount of alcohol [12], for the current study participants were included only if-according to their dinking history interview-they consumed alcohol on a regular drinking occasion that resulted in a corresponding peak BAC of at least 0.08%. The peak BAC was determined by using a modified Widmark formula [27,28], which takes drinking time and the amount of alcohol consumed into account and controls for sex and body weight. When participants reported the absence of an alcohol hangover the day after such a drinking occasion, they were allocated to the hangover-resistant group and when they reported a hangover, they were allocated to the hangover-sensitive group.
Baseline sleep was assessed with the SLEEP-50 questionnaire [29]. The SLEEP-50 comprises 50 items that form nine subscales. The subscales assess sleep apnea, insomnia, narcolepsy, restless legs/periodic leg movement disorder, circadian rhythm sleep disorder, sleepwalking, nightmares, factors influencing sleep, and the impact of sleep complaints on daily functioning. Each item is scored on a 4-point scale: 1 (not at all), 2 (somewhat), 3 (rather much), and 4 (very much). Higher scores on the scales indicate poorer sleep or poorer daytime functioning. Cut-off values for a positive screen for sleep disorders include ≥15 on the sleep apnea scale (sensitivity = 85%, specificity = 88%), ≥19 on the insomnia scale (sensitivity = 71%, specificity = 75%), ≥7 on the restless legs/periodic leg movement disorder scale (sensitivity = 83%, specificity = 72%), and ≥8 on the circadian rhythm sleep disorder scale (sensitivity = 83%, specificity = 69%). In addition to the SLEEP-50, 'common' average total sleep time was recorded, and usual sleep quality was rated on a scale ranging from 0 (very poor) to 10 (very good).

Procedures on Test Days
Visits were scheduled approximately one week apart. However, participants could (last-minute) decide not to drink alcohol on the planned alcohol test day. In that case, the alcohol test day was postponed. All participants completed an alcohol test day and a control test day. On both test days, participants arrived at Utrecht University at 09:00. They received a standardized breakfast (a currant bun and a glass of milk or water) and a similar lunch at midday. They were instructed not to consume caffeinated beverages on test days. Assessments were made throughout the days, at hourly intervals, starting at 09:30 until 15:30.

Single-Time Assessments at Arrival
Participants reported the amount of alcohol they consumed the previous evening, and the start and stop time of alcohol consumption. Guidance was provided on how to report the quantity of alcohol consumed and how to convert drink sizes or bottles to standard units (in The Netherlands, standard units of alcoholic drinks each contain 10 g of alcohol, independent of the type of alcoholic beverage). Bodyweight was measured on each test day, and estimated BAC was computed.
Activities and visited venues during the drinking session and the control evening were recorded. These varied between participants and were categorized as (a) being at home (not active), (b) in the pub (not active), or (c) party (dancing) or sports (active).
Depression was assessed on the alcohol and control day with the Beck's Depression Inventory-II (BDI-II) [23][24][25]. The BDI-II comprises 21 questions which can be scored on a 4-point scale ranging from 0 to 3 based on the severity of each item. The sum of items is computed to represent the overall depression score. Lower scores indicate less severe depressive symptoms. Cut-off ranges for the BDI-II include 29-63 for severe depression, 20-28 for moderate depression, 14-19 for mild depression, and 0-13 for minimal or no depression [25].
On both test days, risk-taking behavior was assessed with the 18-item risk-taking (RT-18) questionnaire [26]. The items have a yes/no answering format (scored 0 or 1, including reversed-scored items). The overall RT-18 score ranges from 0 (no risk-taking) to 18 (extreme risk-taking). The RT-18 has two subscales labeled factor 1 (risk-taking) and factor 2 (risk assessment), with scores ranging from 0 to 9. Higher scores on these scales indicate being engaged in more risk-taking behavior (factor 1) and a poorer assessment of risk (factor 2).
On both test days, the quality of the previous night's sleep was assessed with the Groningen Sleep Quality Scale (GSQS) [21]. Participants answered 14 items on sleep quality (yes/no format). The overall GSQS score ranges from 0 to 14, with higher scores indicating poorer sleep quality. Also recorded was the time to fall asleep and wake up (which enabled the calculation of total sleep time), and the number of nightly awakenings.

Hourly Assessments
Hourly assessments started at 09:30 and ended at 15:30. Overall hangover severity was assessed using a single-item scale ranging from 0 (absent) to 10 (extreme) [30]. Using the same 11-point scale, the severity of 23 individual symptoms that are frequently related to the hangover state were assessed. The symptoms were a combination of the symptoms of three existing hangover scales [31][32][33] and included fatigue, sleepiness, apathy, concentration problems, headache, nausea, regret, heart pounding, heart racing, vomiting, shivering, clumsiness, weakness, dizziness, sweating, stomach pain, confusion, sensitivity to light, sensitivity to sound, thirst, anxiety, depression, and reduced appetite.
The Karolinska Sleepiness Scale (KSS) was completed to rate their current level of sleepiness [19]. Participants could choose one of nine statements, ranging from 'extremely alert' (score of 1) to 'extremely sleepy, fighting sleep' (score of 9). Mood was assessed using a Dutch version of the Profiles of Mood States-Short Form (POMS-SF) [20]. The Dutch POMS-SF consists of 32 items which are scored on a 5-point Likert scale. Scores range from 5 of 51 0 (not at all) to 4 (extremely). The Dutch POMS-SF has five subscales assessing tension, depression, anger, vigor, and fatigue.

Statistical Analysis
Statistical analyses were performed using IBM Statistical Package for the Social Sciences (SPSS), version 29. The analyses compared the outcomes of the hangover-sensitive group and the hangover-resistant group. For demographics and baseline assessments, the comparisons were made with the non-parametric independent-samples Mann-Whitney U test. Percentual data were compared with the Chi-square test (Fischer exact test, 2sided). Differences were considered significant if p < 0.05. For single timepoint assessments, comparisons within groups (alcohol day versus control day) were made with the Related-Samples Wilcoxon Signed Ranks Test. Differences were considered significant if p < 0.05. For multiple timepoint assessments, the groups were compared with the non-parametric Independent-Samples Kruskal-Wallis test. Differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group, after Bonferroni's correction for multiple comparisons, were considered significant if p < 0.0071. Data from the control day and the hangover day were compared within groups with the non-parametric Relatedsamples Friedman's Two-Way Analysis of Variance by Ranks Test. Differences (at the same timepoint) between the control day and the alcohol day, after Bonferroni's correction for multiple comparisons, were considered significant if p < 0.0071.

Results
N = 29 healthy volunteers participated in the study. Of them, 14 were allocated to the hangover-resistant group and 15 to the hangover-sensitive group.

Demographics and Baseline Sleep
Demographics and baseline sleep assessments are summarized in Table 1. The groups did not significantly differ in the assessed demographics or sleep outcomes. Mean and standard deviation (SD) are shown. No significant differences (p < 0.05) were found between the hangover-resistant group and the hangover-sensitive group. Abbreviations: BMI = body mass index, CRSD = circadian rhythm sleep disorder, RLS/PLMD = restless legs/periodic limb movement disorder.

Activity on the Test Days
Participants were free to engage in their usual activities on both test days. A summary of their activities is given in Table 2. On the control day, the majority of participants stayed at home (24 of 29 participants), whereas on the alcohol day about half of the participants went to a pub or party (15 of 29 participants). However, no significant differences were found between the alcohol day and the control day (p = 0.059 for both groups). Moreover, no significant differences in activity were found between the hangover-resistant group and the hangover-sensitive group on the control day (p = 0.481) or the alcohol day (p = 0.401). Table 2. Activity on the test days.

Hangover-Resistant Group
Hangover-Sensitive Group

Variable Control Day Alcohol Day Control Day Alcohol Day
At home (non-active) 13 8 11 6 In pub (non-active) 0 2 1 6 Party (dancing)/sports (active) 1 4 3 3 Number of participants engaged in the activity are listed. No significant differences between the hangover-resistant group and the hangover-sensitive group (p < 0.05) were found.

Estimated Alcohol Consumption
As instructed, participants consumed no alcohol on the control day. Alcohol consumption outcomes for the alcohol day are summarized in Table 3. These were estimated by the participants the morning following drinking. The hangover-resistant group and hangover-sensitive group did not significantly differ in the amount of alcohol consumed or the estimated BAC on the alcohol day. The latter is an important observation, as it warrants a fair comparison of other variables (e.g., the presence and severity of adverse effects) of both groups.

Sleep on Test Days
Sleep quality on the alcohol and control day was assessed with the Groningen Sleep Quality Scale (GSQS). The results are summarized in Table 4. In both groups, on the alcohol day time to bed (TTB), time lights out (TLO), and time falling asleep (TFA) were significantly later compared to the control day. As no significant differences were reported for wake-up time (WUT) on both test days, the corresponding total sleep time (TST) of both groups was significantly shorter on the alcohol day (~75 min shorter in both groups compared to the control day). Thus, for both groups drinking time goes at the expense of total sleep time. Whereas sleep quality was not significantly affected by alcohol consumption in the hangover-resistant group, hangover-sensitive drinkers had a significantly poorer sleep quality score on the alcohol day compared to the control day. On the control day, sleep quality did not differ between the groups. On the alcohol day, sleep quality was significantly poorer in the hangover-sensitive group than in the hangover-resistant group.

Mood Assessments (in the Morning after Arrival)
Directly after arrival in the morning, several mood assessments were made. The outcomes of these assessments on anxiety, depression, and risk-taking behavior are summarized in Table 5. Risk-taking did not differ between the groups or between the alcohol and control days. On the alcohol day, and increase in STAI-S was found for the hangoversensitive group. Mean and standard deviation (SD) are shown. Significant differences between the control day and the alcohol day (p < 0.05) are indicated by *. Significant differences between the hangover-resistant group and the hangoversensitive group (p < 0.05) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangoversensitive group, STAI-T = state train anxiety inventory-trait, STAI-S = state train anxiety inventory-state, BDI-II = Beck's Depression Inventory-II, RT-18 = 18-item risk-taking questionnaire, F1 = factor 1 (risk behavior), F2 = factor 2 (risk assessment).
On average, the anxiety scores on the STAI were below the cut-off of 37, corresponding to no or low anxiety [22]. Moreover, average depression scores on the BDI-II were below 9, indicating no or minimal depression [25]. The clinical relevance of the observed differences between the hangover-resistant group and the hangover-sensitive group is therefore unclear. In the hangover-resistant group, no significant differences in anxiety and depression were found between the control day and the alcohol day. The hangover-sensitive group had a small but significant increase in STAI-State score on the alcohol day. No significant effects on risk-taking behavior were found. Table A1 and Figure 1 summarize the overall hangover severity ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control day. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the overall hangover rating at 09:30 on the alcohol day was 6.1 and then gradually decreased during the day. For all timepoints hangover severity ratings on the alcohol day were significantly higher than those on the control day. On the control day, overall hangover severity ratings were zero in both groups and thus did not significantly differ between the groups. On the alcohol day, for all timepoints, overall hangover severity ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group.

Figure 1.
Overall hangover severity. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A2 and Figure 2 summarize the fatigue ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days, except for a small significant increase at 10:30. The average ratings on both test days remained below 3 (out of 10). For the hangover-sensitive group, the fatigue rating at 09:30 on the alcohol day was 6.0 and then gradually decreased during the day. For all timepoints except 15:30, fatigue ratings on the alcohol day were significantly higher than those on the control day. On the control day, fatigue ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints fatigue ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Overall hangover severity. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A2 and Figure 2 summarize the fatigue ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days, except for a small significant increase at 10:30. The average ratings on both test days remained below 3 (out of 10). For the hangover-sensitive group, the fatigue rating at 09:30 on the alcohol day was 6.0 and then gradually decreased during the day. For all timepoints except 15:30, fatigue ratings on the alcohol day were significantly higher than those on the control day. On the control day, fatigue ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints fatigue ratings of the hangover-sensitive group were significantly higher than those of the hangoverresistant group. Fatigue. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A3 and Figure 3 summarize the sleepiness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 3 (out of 10). For the hangover-sensitive group, the sleepiness rating at 09:30 on the alcohol day was 6.0 and then gradually decreased during the day. For all timepoints except 13:30 and 15:30 sleepiness ratings on the alcohol day were significantly higher than those on the control day. On the control day, sleepiness ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints sleepiness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Fatigue. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A3 and Figure 3 summarize the sleepiness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 3 (out of 10). For the hangover-sensitive group, the sleepiness rating at 09:30 on the alcohol day was 6.0 and then gradually decreased during the day. For all timepoints except 13:30 and 15:30 sleepiness ratings on the alcohol day were significantly higher than those on the control day. On the control day, sleepiness ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints sleepiness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group.

Apathy
Table A4 and Figure 4 summarize the apathy ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the apathy rating at 09:30 on the alcohol day was 3.0 and then gradually decreased during the day. For the timepoints 09:30 to 12:30, apathy ratings on the alcohol day were significantly higher than those on the control day. On the control day, apathy ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints apathy ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Sleepiness. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Apathy
Table A4 and Figure 4 summarize the apathy ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the apathy rating at 09:30 on the alcohol day was 3.0 and then gradually decreased during the day. For the timepoints 09:30 to 12:30, apathy ratings on the alcohol day were significantly higher than those on the control day. On the control day, apathy ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints apathy ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group.  Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Concentration Problems
Table A5 and Figure 5 summarize the concentration problems ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 2 (out of 10). For the hangover-sensitive group, the concentration problems rating at 09:30 on the alcohol day was 5.8 and then gradually Apathy. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Concentration Problems
Table A5 and Figure 5 summarize the concentration problems ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 2 (out of 10). For the hangover-sensitive group, the concentration problems rating at 09:30 on the alcohol day was 5.8 and then gradually decreased during the day. For the timepoints 09:30 to 12:30, concentration problems ratings on the alcohol day were significantly higher than those on the control day. On the control day, concentration problems ratings did not significantly differ between the hangoverresistant group and the hangover-sensitive group. On the alcohol day, for all timepoints concentration problems ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Weakness
Table A6 and Figure 6 summarize the weakness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the weakness rating at 09:30 on the alcohol day was 3.8 and then gradually decreased during the day. For all timepoints except 15:30 weakness ratings on the alcohol day were significantly higher than those on the control day. On the control day, weakness ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints except 15:30 weakness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Weakness
Table A6 and Figure 6 summarize the weakness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the weakness rating at 09:30 on the alcohol day was 3.8 and then gradually decreased during the day. For all timepoints except 15:30 weakness ratings on the alcohol day were significantly higher than those on the control day. On the control day, weakness ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints except 15:30 weakness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Weakness. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Clumsiness
Table A7 and Figure 7 summarize the clumsiness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the clumsiness rating at 09:30 on the alcohol day was 4.2 and then gradually decreased during the day. For all timepoints except 15:30, clumsiness ratings on the alcohol day were significantly higher than those on the control day. On the control day, clumsiness ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints clumsiness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Weakness. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Clumsiness
Table A7 and Figure 7 summarize the clumsiness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the clumsiness rating at 09:30 on the alcohol day was 4.2 and then gradually decreased during the day. For all timepoints except 15:30, clumsiness ratings on the alcohol day were significantly higher than those on the control day. On the control day, clumsiness ratings did not significantly differ between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, for all timepoints clumsiness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group.

Confusion
Table A8 and Figure 8 summarize the confusion ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the confusion rating at 09:30 on the alcohol day was 2.1 and then gradually decreased during the day. However, no significant differences were found between the alcohol and control day. On both the control and alcohol day, no significant differences in confusion ratings were found between the hangover-resistant group and the hangover-sensitive group, except at 12:30 on the alcohol day when the confusion rating was significantly higher in the hangover-sensitive group. Clumsiness. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Confusion
Table A8 and Figure 8 summarize the confusion ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the confusion rating at 09:30 on the alcohol day was 2.1 and then gradually decreased during the day. However, no significant differences were found between the alcohol and control day. On both the control and alcohol day, no significant differences in confusion ratings were found between the hangover-resistant group and the hangover-sensitive group, except at 12:30 on the alcohol day when the confusion rating was significantly higher in the hangover-sensitive group. Confusion. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Headache
Table A9 and Figure 9 summarize the headache ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both Confusion. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Headache
Table A9 and Figure 9 summarize the headache ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. The average ratings on both test days remained below 1 (out of 10). For the hangover-sensitive group, the headache rating at 09:30 on the alcohol day was 4.4 and then gradually decreased during the day. Significant differences were found between the alcohol and control days from 09:30 to 11:30 and at 13:30. On the control day, no significant differences in headache ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, at each timepoint headache ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Headache. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Stomach Pain
Table A10 and Figure 10 summarize the stomach pain ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average stomach pain ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the stomach pain rating at 09:30 on the alcohol day was 3.1 and then gradually decreased during the day. On the control day, no significant differences in stomach pain ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, at each timepoint except 14:30 stomach pain ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Headache. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Stomach Pain
Table A10 and Figure 10 summarize the stomach pain ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average stomach pain ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the stomach pain rating at 09:30 on the alcohol day was 3.1 and then gradually decreased during the day. On the control day, no significant differences in stomach pain ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, at each timepoint except 14:30 stomach pain ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Figure 10. Stomach pain. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A11 and Figure 11 summarize the nausea ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average nausea ratings of the hangover-resistant group remained below 2 (out of 10). For the hangover-sensitive group, the nausea rating at 09:30 on the alcohol day was 4.5 and then gradually decreased during the day. Significantly higher nausea ratings on the alcohol day were found for each timepoint except at 12:30. On the control day, no significant differences in nausea ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, at each timepoint nausea ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. Figure 10. Stomach pain. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A11 and Figure 11 summarize the nausea ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average nausea ratings of the hangover-resistant group remained below 2 (out of 10). For the hangover-sensitive group, the nausea rating at 09:30 on the alcohol day was 4.5 and then gradually decreased during the day. Significantly higher nausea ratings on the alcohol day were found for each timepoint except at 12:30. On the control day, no significant differences in nausea ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, at each timepoint nausea ratings of the hangover-sensitive group were significantly higher than those of the hangoverresistant group.

Vomiting
Table A12 and Figure 12 summarize the vomiting ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and hangover-sensitive group, no significant differences were found between the alcohol and control day. On both test days, the average vomiting rating of the hangover-resistant group remained below 2 (out of 10), and the average vomiting rating for the hangover-sensitive group remained below 1. On both the control day and the alcohol day, no significant differences in vomiting ratings were found between the hangover-resistant group and the hangover-sensitive group. Figure 11. Nausea. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A12 and Figure 12 summarize the vomiting ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and hangover-sensitive group, no significant differences were found between the alcohol and control day. On both test days, the average vomiting rating of the hangover-resistant group remained below 2 (out of 10), and the average vomiting rating for the hangoversensitive group remained below 1. On both the control day and the alcohol day, no significant differences in vomiting ratings were found between the hangover-resistant group and the hangover-sensitive group. Figure 11. Nausea. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Vomiting. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Shivering
Table A13 and Figure 13 summarize the shivering ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant Vomiting. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A13 and Figure 13 summarize the shivering ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average shivering ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the shivering rating at 09:30 on the alcohol day was 2.4 and then gradually decreased during the day. Significantly higher shivering ratings on the alcohol day compared to the control day were found at 09:30 and 11:30. On the control day, no significant differences in shivering ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, the shivering ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group from 10:30 to 14:30. Shivering. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Dizziness
Table A14 and Figure 14 summarize the dizziness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average dizziness ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the dizziness rating at 09:30 on the alcohol day was 3.1 and then gradually decreased during the day. Significantly higher dizziness ratings on the alcohol day compared to the control day were found from 09:30 to 12:30. On the control day, no significant differences in dizziness ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, the dizziness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group at each timepoint except 09:30 and 14:30. Shivering. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A14 and Figure 14 summarize the dizziness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average dizziness ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the dizziness rating at 09:30 on the alcohol day was 3.1 and then gradually decreased during the day. Significantly higher dizziness ratings on the alcohol day compared to the control day were found from 09:30 to 12:30. On the control day, no significant differences in dizziness ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, the dizziness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group at each timepoint except 09:30 and 14:30. Dizziness. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Sensitivity to Light
Table A15 and Figure 15 summarize the sensitivity to light ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average sensitivity to light ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the sensitivity to light rating at 09:30 on the alcohol day was 2.9 and then gradually decreased during the day. Significantly higher sensitivity to light ratings on the alcohol day compared to the control day were found from 09:30 to 11:30. On the control day, no significant differences in the sensitivity to light ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, the sensitivity to light ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group from 09:30 to 12:30. Dizziness. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Sensitivity to Light
Table A15 and Figure 15 summarize the sensitivity to light ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average sensitivity to light ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the sensitivity to light rating at 09:30 on the alcohol day was 2.9 and then gradually decreased during the day. Significantly higher sensitivity to light ratings on the alcohol day compared to the control day were found from 09:30 to 11:30. On the control day, no significant differences in the sensitivity to light ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, the sensitivity to light ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group from 09:30 to 12:30.

Sensitivity to Sound
Table A16 and Figure 16 summarize the sensitivity to sound ratings of the hangoverresistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average sensitivity to sound ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the sensitivity to sound rating at 09:30 on the alcohol day was 2.4 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in sensitivity to sound ratings were found between the hangover-resistant group and the hangover-sensitive group. Figure 15. Sensitivity to light. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Sensitivity to Sound
Table A16 and Figure 16 summarize the sensitivity to sound ratings of the hangoverresistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average sensitivity to sound ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the sensitivity to sound rating at 09:30 on the alcohol day was 2.4 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in sensitivity to sound ratings were found between the hangover-resistant group and the hangover-sensitive group. . Sensitivity to sound. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A17 and Figure 17 summarize the sweating ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average sweating ratings of the hangover-resistant Figure 16. Sensitivity to sound. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A17 and Figure 17 summarize the sweating ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average sweating ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the sweating rating at 09:30 on the alcohol day was 1.3 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in sweating ratings were found between the hangover-resistant group and the hangover-sensitive group. Sweating. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Heart Pounding
Table A18 and Figure 18 summarize the heart-pounding ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control day. On both test days, the average heart-pounding ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the heart-pounding rating at 09:30 on the alcohol day was 1.5 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in heart-pounding ratings were found between the hangover-resistant group and the hangover-sensitive group. Sweating. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Heart Pounding
Table A18 and Figure 18 summarize the heart-pounding ratings of the hangoverresistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control day. On both test days, the average heart-pounding ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the heart-pounding rating at 09:30 on the alcohol day was 1.5 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in heart-pounding ratings were found between the hangover-resistant group and the hangover-sensitive group. Figure 18. Heart pounding. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A19 and Figure 19 summarize the heart-racing ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average heart-racing ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the heart racing rating at 09:30 on the alcohol day was 1.3 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in heart-racing ratings were found between the hangover-resistant group and the hangoversensitive group. Figure 18. Heart pounding. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A19 and Figure 19 summarize the heart-racing ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average heart-racing ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the heart racing rating at 09:30 on the alcohol day was 1.3 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in heart-racing ratings were found between the hangover-resistant group and the hangover-sensitive group.

Thirst
Table A20 and Figure 20 summarize the thirst ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average thirst ratings of the hangover-resistant group remained below 2 (out of 10). For the hangover-sensitive group, the thirst rating at 09:30 on the alcohol day was 5.3 and then gradually decreased during the day. Significantly higher thirst ratings on the alcohol day compared to the control day were found at 09:30 and 10:30. On the control day, no significant differences in thirst ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, the thirst ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group from 09:30 to 11:30 and at 13:30 and 14:30. Figure 19. Heart racing. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Thirst
Table A20 and Figure 20 summarize the thirst ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average thirst ratings of the hangover-resistant group remained below 2 (out of 10). For the hangover-sensitive group, the thirst rating at 09:30 on the alcohol day was 5.3 and then gradually decreased during the day. Significantly higher thirst ratings on the alcohol day compared to the control day were found at 09:30 and 10:30. On the control day, no significant differences in thirst ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, the thirst ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group from 09:30 to 11:30 and at 13:30 and 14:30. Figure 19. Heart racing. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Regret
Table A21 and Figure 21 summarize the regret ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average regret ratings of the hangover-resistant group

Regret
Table A21 and Figure 21 summarize the regret ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangoversensitive group, no significant differences were found between the alcohol and control days. On both test days, the average regret ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the regret rating at 09:30 on the alcohol day was 1.9 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in regret ratings were found between the hangover-resistant group and the hangover-sensitive group. Regret. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Anxiety
Table A22 and Figure 22 summarize the anxiety ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average anxiety ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the anxiety rating at 09:30 on the alcohol day was 1.2 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in anxiety ratings were found between the hangover-resistant group and the hangover-sensitive group. Regret. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Anxiety
Table A22 and Figure 22 summarize the anxiety ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average anxiety ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the anxiety rating at 09:30 on the alcohol day was 1.2 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in anxiety ratings were found between the hangover-resistant group and the hangover-sensitive group. Figure 22. Anxiety. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Depression
Table A23 and Figure 23 summarize the depression ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average depression ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the depression rating at 09:30 on the alcohol day was 1.2 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in depression ratings were found between the hangover-resistant group and the hangover-sensitive group. Anxiety. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found.

Depression
Table A23 and Figure 23 summarize the depression ratings of the hangover-resistant group and the hangover-sensitive group. For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol and control days. On both test days, the average depression ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the depression rating at 09:30 on the alcohol day was 1.2 and then gradually decreased during the day. On both the control day and the alcohol day, no significant differences in depression ratings were found between the hangover-resistant group and the hangover-sensitive group.

Reduced Appetite
Table A24 and Figure 24 summarize the reduced appetite ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average reduced appetite ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the reduced appetite rating at 09:30 on the alcohol day was 4.3 and then gradually decreased during the day. Significantly higher reduced appetite ratings on the alcohol day compared to the control day were found at 09:30, 10:30, 12:30, and 14:30. On the control day, no significant differences in reduced appetite ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, reduced appetite ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group from 09:30 to 12:30 and at 14:30. Depression. Mean and standard error (SE) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A24 and Figure 24 summarize the reduced appetite ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, no significant differences were found between the alcohol and control days. On both test days, the average reduced appetite ratings of the hangover-resistant group remained below 1 (out of 10). For the hangover-sensitive group, the reduced appetite rating at 09:30 on the alcohol day was 4.3 and then gradually decreased during the day. Significantly higher reduced appetite ratings on the alcohol day compared to the control day were found at 09:30, 10:30, 12:30, and 14:30. On the control day, no significant differences in reduced appetite ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, reduced appetite ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group from 09:30 to 12:30 and at 14:30.

Karoliska Sleepiness Scale (KSS)
Table A25 and Figure 25 summarize the KSS sleepiness ratings of the hangover-resistant group and the hangover-sensitive group. For the hangover-resistant group, KSS sleepiness ratings were higher on the alcohol day than on the control day; however, the difference was statistically significant only at 10:30. On both test days, KSS sleepiness rat- Figure 24. Reduced appetite. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Karoliska Sleepiness Scale (KSS)
Table A25 and Figure 25 summarize the KSS sleepiness ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, KSS sleepiness ratings were higher on the alcohol day than on the control day; however, the difference was statistically significant only at 10:30. On both test days, KSS sleepiness ratings of the hangover-resistant group remained below 6 (out of 10). For the hangoversensitive group, the KSS sleepiness rating at 09:30 on the alcohol day was 7.1, remained high until 12:30, and then gradually decreased. Significantly higher KSS sleepiness ratings on the alcohol day compared to the control day were found at all timepoints except 13:30 and 15:30. On the control day, no significant differences in KSS sleepiness ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, at all timepoints the KSS sleepiness ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group.  Table A26 and Figure 26 summarize the POMS-SF-Depression ratings of the hangover-resistant group and the hangover-sensitive group. For both groups, no significant differences were found between the alcohol day and the control day. On both test days, the POMS-SF-Depression ratings of both groups remained below 4 (out of 32). On both the control day and the alcohol day, no significant differences were found between the hangover-resistant group and the hangover-sensitive group. Figure 25. Karolinska Sleepiness Scale. Mean and standard error (SE) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A26 and Figure 26 summarize the POMS-SF-Depression ratings of the hangoverresistant group and the hangover-sensitive group. For both groups, no significant differences were found between the alcohol day and the control day. On both test days, the POMS-SF-Depression ratings of both groups remained below 4 (out of 32). On both the control day and the alcohol day, no significant differences were found between the hangover-resistant group and the hangover-sensitive group. Figure 26. POMS-SF-Depression. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A27 and Figure 27 summarize the POMS-SF-Anger ratings of the hangoverresistant group and the hangover-sensitive group. On both test days, the POMS-SF-Anger ratings of both groups remained below 1 (out of 28). For the hangover-resistant group, no significant differences were found between the alcohol day and the control day. For the hangover-sensitive group, the POMS-SF-Anger rating at 09:30 on the alcohol day was 3.4, and then gradually decreased during the day. However, a significant increase in POMS-SF-Anger ratings was found only at 10:30. On both the control day and the alcohol day, no significant differences were found between the hangover-resistant group and the hangover-sensitive group. Figure 26. POMS-SF-Depression. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A27 and Figure 27 summarize the POMS-SF-Anger ratings of the hangoverresistant group and the hangover-sensitive group. On both test days, the POMS-SF-Anger ratings of both groups remained below 1 (out of 28). For the hangover-resistant group, no significant differences were found between the alcohol day and the control day. For the hangover-sensitive group, the POMS-SF-Anger rating at 09:30 on the alcohol day was 3.4, and then gradually decreased during the day. However, a significant increase in POMS-SF-Anger ratings was found only at 10:30. On both the control day and the alcohol day, no significant differences were found between the hangover-resistant group and the hangover-sensitive group.

POMS-SF-Tension
Table A28 and Figure 28 summarize the POMS-SF-Tension ratings of the hangoverresistant group and the hangover-sensitive group. On both test days, the POMS-SF-Tension ratings of both groups were ≤2 (out of 24). For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol day and the control day. On the control day, no significant differences were found between the groups. For the alcohol day, the POMS-SF-Tension rating of the hangoversensitive group was significantly higher than that of the hangover-resistant group at 12:30, but no significant differences between the groups were found at other timepoints. Figure 27. POMS-SF-Anger. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Table A28 and Figure 28 summarize the POMS-SF-Tension ratings of the hangoverresistant group and the hangover-sensitive group. On both test days, the POMS-SF-Tension ratings of both groups were ≤2 (out of 24). For both the hangover-resistant group and the hangover-sensitive group, no significant differences were found between the alcohol day and the control day. On the control day, no significant differences were found between the groups. For the alcohol day, the POMS-SF-Tension rating of the hangoversensitive group was significantly higher than that of the hangover-resistant group at 12:30, but no significant differences between the groups were found at other timepoints. . POMS-SF-Tension. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A29 and Figure 29 summarize the POMS-SF-Fatigue ratings of the hangoverresistant group and the hangover-sensitive group. On both test days, the POMS-SF-Fatigue ratings of the hangover-resistant group were below 2 (out of 24). For the hangover- Figure 28. POMS-SF-Tension. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A29 and Figure 29 summarize the POMS-SF-Fatigue ratings of the hangoverresistant group and the hangover-sensitive group. On both test days, the POMS-SF-Fatigue ratings of the hangover-resistant group were below 2 (out of 24). For the hangoversensitive group, the POMS-SF-Fatigue rating at 09:30 on the alcohol day was 10.3 and then gradually decreased during the day. Significantly higher POMS-SF-Fatigue ratings on the alcohol day compared to the control day were found at all timepoints except 15:30. On the control day, no significant differences in POMS-SF-Fatigue ratings were found between the hangover-resistant group and the hangover-sensitive group. On the alcohol day, at all timepoints POMS-SF-Fatigue ratings of the hangover-sensitive group were significantly higher than those of the hangover-resistant group. . POMS-SF-Fatigue. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A30 and Figure 30 summarize the POMS-SF-Vigor ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, on both test days, the POMS-SF-Vigor ratings were highest in the morning and then gradually decreased during the day. From 09:30 to 11:30 the POMS-SF-Vigor ratings on the alcohol day were significantly lower compared to the control day. For the hangover-sensitive group, the POMS-SF-Vigor ratings of the control day did not significantly differ from those of the hangover-resistant group. However, the POMS-SF-Vigor rating at 09:30 on the alcohol day was 2.8 and then gradually increased to 4.6 at 15:30. Significantly lower POMS-SF-Vigor ratings on the alcohol day compared to the control day were found at all timepoints except 15:30. On the alcohol day, at all timepoints except 13:30 and 15:30 the POMS-SF-Vigor ratings of the hangover-sensitive group were significantly lower than those of the hangover-resistant group. Figure 29. POMS-SF-Fatigue. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡. Table A30 and Figure 30 summarize the POMS-SF-Vigor ratings of the hangoverresistant group and the hangover-sensitive group. For the hangover-resistant group, on both test days, the POMS-SF-Vigor ratings were highest in the morning and then gradually decreased during the day. From 09:30 to 11:30 the POMS-SF-Vigor ratings on the alcohol day were significantly lower compared to the control day. For the hangover-sensitive group, the POMS-SF-Vigor ratings of the control day did not significantly differ from those of the hangover-resistant group. However, the POMS-SF-Vigor rating at 09:30 on the alcohol day was 2.8 and then gradually increased to 4.6 at 15:30. Significantly lower POMS-SF-Vigor ratings on the alcohol day compared to the control day were found at all timepoints except 15:30. On the alcohol day, at all timepoints except 13:30 and 15:30 the POMS-SF-Vigor ratings of the hangover-sensitive group were significantly lower than those of the hangover-resistant group. Figure 30. POMS-SF-Vigor. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Predictors of Overall Hangover Severity
It is evident from the previous sections that both the overall hangover severity and the severity of individual items reported by hangover-sensitive drinkers vary during the day. Overall, the intensity of symptoms is greatest in the morning assessments and then gradually declines during the day. There is, however, a difference in the rate of decline between symptoms, and whereas the severity of some symptoms is still significantly greater at 15:30 on the alcohol day compared to the control day, this is not the case for other symptoms. With the latter in mind, a series of stepwise linear regression analyses were conducted to identify predictors of overall hangover severity for each timepoint. Only participants of the hangover-sensitive group were included. Included independent variables were all 23 individual symptoms, KSS sleepiness, the POMS-SF mood subscales, sleep quality (assessed with the Groningen Sleep Quality Scale), the amount of alcohol consumed, and estimated BAC. The results of the analyses for the morning, midday, and afternoon assessments are summarized in Figures A1-A3, respectively.
Comparing the analyses of the different timepoints reveals that in the morning and midday, the predictors that explain the most variance in overall hangover severity are clumsiness, concentration problems, and headache (See Figures A1 and A2). In contrast, in the afternoon the most contributing predictors include nausea and vomiting, sleepiness (assessed with the KSS), and previous night sleep quality (See Figure A3). The outcomes confirm that previous night sleep quality, daytime sleepiness, headache, and nausea are core determinants of overall hangover severity.
Interestingly, mood factors, either assessed as individual items or via the POMS-SF, have no or only a very small contribution to the models that predict overall hangover severity. This finding is in line with the fact that mood changes during the hangover state are usually only modest and reported by a minority of drinkers [4]. Also of interest are Figure 30. POMS-SF-Vigor. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡.

Predictors of Overall Hangover Severity
It is evident from the previous sections that both the overall hangover severity and the severity of individual items reported by hangover-sensitive drinkers vary during the day. Overall, the intensity of symptoms is greatest in the morning assessments and then gradually declines during the day. There is, however, a difference in the rate of decline between symptoms, and whereas the severity of some symptoms is still significantly greater at 15:30 on the alcohol day compared to the control day, this is not the case for other symptoms. With the latter in mind, a series of stepwise linear regression analyses were conducted to identify predictors of overall hangover severity for each timepoint. Only participants of the hangover-sensitive group were included. Included independent variables were all 23 individual symptoms, KSS sleepiness, the POMS-SF mood subscales, sleep quality (assessed with the Groningen Sleep Quality Scale), the amount of alcohol consumed, and estimated BAC. The results of the analyses for the morning, midday, and afternoon assessments are summarized in Figures A1-A3, respectively.
Comparing the analyses of the different timepoints reveals that in the morning and midday, the predictors that explain the most variance in overall hangover severity are clumsiness, concentration problems, and headache (See Figures A1 and A2). In contrast, in the afternoon the most contributing predictors include nausea and vomiting, sleepiness (assessed with the KSS), and previous night sleep quality (See Figure A3). The outcomes confirm that previous night sleep quality, daytime sleepiness, headache, and nausea are core determinants of overall hangover severity.
Interestingly, mood factors, either assessed as individual items or via the POMS-SF, have no or only a very small contribution to the models that predict overall hangover severity. This finding is in line with the fact that mood changes during the hangover state are usually only modest and reported by a minority of drinkers [4]. Also of interest are the findings regarding thirst. Although thirst is one of the most frequently reported symptoms with a high severity score, only at one timepoint (11:30) thirst appeared to be a minor determinant of overall hangover severity (contributing 12.7% to the model).

Discussion
In this semi-naturalistic study, a comprehensive and detailed comparison was made between the next-day effects of an evening of alcohol consumption between hangoversensitive drinkers and hangover-resistant drinkers. As a start, it is important to note that the two groups did not significantly differ from each other on demographic characteristics and baseline sleep. On the alcohol test day, both groups consumed a considerable amount of alcohol that should be sufficient to elicit a hangover in sensitive drinkers. Of importance for a fair comparison between the hangover-sensitive group and the hangover-resistant group, no significant differences were found in the amount of alcohol consumed on the alcohol day, the estimated BAC, and the start and stop time of alcohol consumption. The groups did also not differ in reported activities on the test days. Both groups slept significantly shorter on the alcohol day compared to the control day. Although no significant differences were found on any of the sleep outcomes (e.g., time to bed, total sleep time) between the two groups on either the alcohol or the control day, the hangover-sensitive group did report a significantly poorer sleep quality on the alcohol day compared to the hangover-resistant group. The morning assessments also reported no clinically relevant differences between the alcohol and control day or between the groups for anxiety (STAI-Y), depression (BDI-II), and risk-taking behavior (RT-18). Taken together, a fair comparison between the next-day effects of an evening of alcohol consumption between the hangover-sensitive group and the hangover-resistant group is warranted.
The outcomes of the next-day symptom assessments revealed significant differences between the two groups. In the hangover-sensitive group, a variety of symptoms were reported the day following alcohol consumption. Their presence and severity are summarized in Figure 31. the findings regarding thirst. Although thirst is one of the most frequently reported symptoms with a high severity score, only at one timepoint (11:30) thirst appeared to be a minor determinant of overall hangover severity (contributing 12.7% to the model).

Discussion
In this semi-naturalistic study, a comprehensive and detailed comparison was made between the next-day effects of an evening of alcohol consumption between hangoversensitive drinkers and hangover-resistant drinkers. As a start, it is important to note that the two groups did not significantly differ from each other on demographic characteristics and baseline sleep. On the alcohol test day, both groups consumed a considerable amount of alcohol that should be sufficient to elicit a hangover in sensitive drinkers. Of importance for a fair comparison between the hangover-sensitive group and the hangover-resistant group, no significant differences were found in the amount of alcohol consumed on the alcohol day, the estimated BAC, and the start and stop time of alcohol consumption. The groups did also not differ in reported activities on the test days. Both groups slept significantly shorter on the alcohol day compared to the control day. Although no significant differences were found on any of the sleep outcomes (e.g., time to bed, total sleep time) between the two groups on either the alcohol or the control day, the hangover-sensitive group did report a significantly poorer sleep quality on the alcohol day compared to the hangover-resistant group. The morning assessments also reported no clinically relevant differences between the alcohol and control day or between the groups for anxiety (STAI-Y), depression (BDI-II), and risk-taking behavior (RT-18). Taken together, a fair comparison between the next-day effects of an evening of alcohol consumption between the hangover-sensitive group and the hangover-resistant group is warranted.
The outcomes of the next-day symptom assessments revealed significant differences between the two groups. In the hangover-sensitive group, a variety of symptoms were reported the day following alcohol consumption. Their presence and severity are summarized in Figure 31.  The most frequently reported symptoms by hangover-sensitive drinkers at 09:30 are sleepiness, concentration problems, and thirst. These symptoms had also the highest severity scores. Other symptoms with high presence and severity were fatigue, clumsi-ness, weakness, nausea, and headache. The least frequently reported symptom, with the lowest severity score, was anxiety. The severity of symptoms declined throughout the day. However, for most symptoms throughout the day, significantly higher severity scores were reported on the alcohol day compared to the control day. The KSS assessment revealed a significantly increased sleepiness throughout the alcohol day. In line, the POMS-SF mood assessments revealed significantly increased fatigue scores and significantly reduced vigor. No significant effects were found for depression and tension, whereas a significant increase in anger on the alcohol day was found only at 10:30. No significant differences between the alcohol and control day were found for confusion, stomach pain, vomiting, sensitivity to sound, sweating, heart pounding, heart racing, regret, anxiety, and depression. On first thought, it could be questioned if these symptoms should be considered hangover-related. Alternatively, one could argue that these symptoms are indeed less frequently reported, but that severity scores of these symptoms by those who do report them are comparable to those of other symptoms. Figure 32 shows the average severity scores of only those participants of the hangoversensitive group that reported the corresponding symptom. It is evident that the severity scores of most symptoms are in the range of 3 to 6, corresponding to moderate intensity. Given this, one should conclude that these symptoms are also relevant, though less frequently reported. Whereas research usually reports results at the group level (e.g., averages), the data presented in Figure 32 advocate that it is also important to look at individual study participants. Whereas at the group level, an average symptom may be low, individual drinkers may experience such symptoms with high intensity.
The most frequently reported symptoms by hangover-sensitive drinkers at 09:30 are sleepiness, concentration problems, and thirst. These symptoms had also the highest severity scores. Other symptoms with high presence and severity were fatigue, clumsiness, weakness, nausea, and headache. The least frequently reported symptom, with the lowest severity score, was anxiety. The severity of symptoms declined throughout the day. However, for most symptoms throughout the day, significantly higher severity scores were reported on the alcohol day compared to the control day. The KSS assessment revealed a significantly increased sleepiness throughout the alcohol day. In line, the POMS-SF mood assessments revealed significantly increased fatigue scores and significantly reduced vigor. No significant effects were found for depression and tension, whereas a significant increase in anger on the alcohol day was found only at 10:30. No significant differences between the alcohol and control day were found for confusion, stomach pain, vomiting, sensitivity to sound, sweating, heart pounding, heart racing, regret, anxiety, and depression. On first thought, it could be questioned if these symptoms should be considered hangover-related. Alternatively, one could argue that these symptoms are indeed less frequently reported, but that severity scores of these symptoms by those who do report them are comparable to those of other symptoms. Figure 32 shows the average severity scores of only those participants of the hangover-sensitive group that reported the corresponding symptom. It is evident that the severity scores of most symptoms are in the range of 3 to 6, corresponding to moderate intensity. Given this, one should conclude that these symptoms are also relevant, though less frequently reported. Whereas research usually reports results at the group level (e.g., averages), the data presented in Figure 32 advocate that it is also important to look at individual study participants. Whereas at the group level, an average symptom may be low, individual drinkers may experience such symptoms with high intensity. The presence and severity of most next-day symptoms of the hangover-resistant group are summarized in Figure 33. In contrast, none of the next-day symptoms at 09:30 reported by the hangover-resistant group differed significantly between the alcohol and The presence and severity of most next-day symptoms of the hangover-resistant group are summarized in Figure 33. In contrast, none of the next-day symptoms at 09:30 reported by the hangover-resistant group differed significantly between the alcohol and control days. At other timepoints, only fatigue at 10:30 was significantly higher on the alcohol day (1.64) than on the control day (0.57). Most symptom scores were below 1 on the 0 to 10 severity scale. The presence and severity of most next-day symptoms were significantly lower compared to those reported by the hangover-sensitive group. control days. At other timepoints, only fatigue at 10:30 was significantly higher on the alcohol day (1.64) than on the control day (0.57). Most symptom scores were below 1 on the 0 to 10 severity scale. The presence and severity of most next-day symptoms were significantly lower compared to those reported by the hangover-sensitive group. On the KSS, sleepiness scores on the alcohol day were significantly increased at 10:30. At other timepoints, the increase did not reach statistical significance. Regarding the POMS-SF mood assessments, no significant differences between the alcohol and control days were found for depression, anger, fatigue, and tension. However, significant reductions in vigor were reported on the alcohol day at 09:30, 10:30, and 11:30.
Taken together, the next-day adverse effects reported by hangover-resistant drinkers, if any, are limited to mild sleepiness-related effects and reduced vigor in the morning. These effects can be due to alcohol, but it is more likely that these are related to the sleep loss associated with the alcohol day.
Our findings are in line with the study conducted by Hogewoning et al. [16]. The current study extends these findings by conducting assessments at multiple timepoints throughout the day. The outcomes of these assessments reveal that symptom severity is most severe in the morning hours and then gradually decreases. However, in the afternoon at 15:30, hangover-sensitive drinkers still report a great number of symptoms that are significantly more severe on the alcohol day compared to the control day. Moreover, at that time, overall hangover severity is still evident (a score of 3.2 out of 10). These findings demonstrate that hangovers are not limited to the morning hours. Although the intensity of experienced symptoms and overall hangover severity declines during the day, they persist throughout the day.
The observation that symptoms such as sleepiness and concentration problems persist up to 15 h after alcohol consumption may have significant implications for daytime functioning. For example, previous studies found that driving ability is significantly impaired in the hangover state [34,35]. These studies assessed simulated driving performance in the morning. The fact that symptoms persist throughout the day may imply that On the KSS, sleepiness scores on the alcohol day were significantly increased at 10:30. At other timepoints, the increase did not reach statistical significance. Regarding the POMS-SF mood assessments, no significant differences between the alcohol and control days were found for depression, anger, fatigue, and tension. However, significant reductions in vigor were reported on the alcohol day at 09:30, 10:30, and 11:30.
Taken together, the next-day adverse effects reported by hangover-resistant drinkers, if any, are limited to mild sleepiness-related effects and reduced vigor in the morning. These effects can be due to alcohol, but it is more likely that these are related to the sleep loss associated with the alcohol day.
Our findings are in line with the study conducted by Hogewoning et al. [16]. The current study extends these findings by conducting assessments at multiple timepoints throughout the day. The outcomes of these assessments reveal that symptom severity is most severe in the morning hours and then gradually decreases. However, in the afternoon at 15:30, hangover-sensitive drinkers still report a great number of symptoms that are significantly more severe on the alcohol day compared to the control day. Moreover, at that time, overall hangover severity is still evident (a score of 3.2 out of 10). These findings demonstrate that hangovers are not limited to the morning hours. Although the intensity of experienced symptoms and overall hangover severity declines during the day, they persist throughout the day.
The observation that symptoms such as sleepiness and concentration problems persist up to 15 h after alcohol consumption may have significant implications for daytime functioning. For example, previous studies found that driving ability is significantly impaired in the hangover state [34,35]. These studies assessed simulated driving performance in the morning. The fact that symptoms persist throughout the day may imply that driving will also be impaired in the afternoon. Up to now, only a few studies investigated alcohol hangover effects at different timepoints during the day, with mixed results on the impact of the hangover state on mood, cognition, and performance of psychometric tests [36][37][38]. Future studies should therefore also assess the impact of alcohol hangovers on daytime performance (e.g., driving, work) at different timepoints during the day.
An explanation for the differences between hangover-sensitive drinkers and hangoverresistant drinkers may be related to the fact that sleep quality on the alcohol day was reported as significantly poorer by the hangover-sensitive group than the hangover-resistant group. Previous research has linked poor sleep quality to hangover severity and next-day sleepiness-related symptoms [39][40][41][42][43][44][45]. However, poor sleep quality and sleep loss without alcohol consumption may also result in next-day sleepiness, fatigue, and concentration problems [46], and have also been associated with other frequently reported hangover symptoms such as headache [47,48] and nausea [49]. One could also argue that participants perceived their sleep quality as worse because they experienced daytime sleepiness-related symptoms at the time they completed the sleep scale in the morning. The latter may be a possible explanation, given the fact that no other significant differences were found between the groups on any of the other sleep outcomes, including total sleep time, time to bed, wake-up time, and the number of nightly awakenings.
Differences between hangover-sensitive drinkers and hangover-resistant drinkers in outcomes of biomarker assessment that were conducted among participants of the study by Hogewoning et al. [16] may provide an alternative explanation. In this study, saliva and urine were collected in the morning on the alcohol day and the control day. Potential biomarkers were assessed and compared between the hangover-sensitive group and the hangover-resistant group. For both test days, no significant differences between the groups were found for urine concentrations of methanol [50], urine concentrations of ethanol metabolites ethyl glucuronide (EtG) and ethyl sulfate (EtS) [51], and 5-hydroxytryptophol (5-HTOL), 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HTOL/5-HIAA ratio [52]. In both groups, the urine concentrations of these biomarkers were increased the morning after alcohol consumption, but their concentration did not correlate with hangover severity. In contrast, although both groups reported having consumed a comparable amount of alcohol, urine ethanol concentrations in the hangover-resistant group were significantly lower compared to those of the hangover-sensitive group [53]. This finding suggests that hangover-resistant drinkers may have an accelerated alcohol metabolism, which may explain why they experience no hangover symptoms [9]. Another study in a small sample of hangover-sensitive drinkers confirmed that their alcohol breakdown rate was significantly and negatively correlated with hangover severity [10]. Another study [10] found that more oxidative stress, measured as the presence of malondialdehyde in blood, in the first hours after alcohol consumption was associated with reporting less severe hangovers, whereas the presence of more malondialdehyde at a later timepoint was associated with having more severe hangovers. Thus, a quicker elimination of ethanol was associated with reporting less severe hangovers. However, a direct comparison between hangover-sensitive drinkers and hangover-resistant drinkers revealed no significant differences in alcohol breakdown rate after an alcohol challenge [54]. The amount of alcohol administered in this study was, however, low (resulting in a peak BAC of 0.05%). It might be that differences in alcohol metabolism between hangover-sensitive drinkers and hangover-resistant drinkers manifest only at higher BACs. In addition to alcohol metabolism, other analyses focused on the inflammatory response caused by alcohol. Saliva samples from the participants of the study of Hogewoning et al. [16] were analyzed to assess the concentration of a variety of cytokines [55]. Compared to the control day, on the alcohol day significant increases in saliva interleukin (IL)-6 and IL-10 concentrations were found in both groups. However, no significant differences were found between the groups. Moreover, changes in cytokine concentration (alcohol day-control day) did not significantly correlate with hangover severity [55]. These observations were unexpected, as previous survey research suggested that the perceived immune fitness of hangover-resistant drinkers was significantly better that that reported by hangover-sensitive drinkers [56]. Moreover, another study that conducted cytokine assessments in the blood instead of saliva found significant correlations between changes (alcohol day-control day) in IL-12 and interferon (IFN)-γ with overall hangover severity [57]. The course of biological parameters, including biomarkers of systemic inflammation, hormones, and physiological effects should be further evaluated in future studies.
Taken together, there is presently limited research with inconsistent findings on the role of alcohol metabolism and the inflammatory response to alcohol consumption in the pathology of alcohol hangovers. More research is needed to elucidate the pathology of the hangover and to investigate and explain why some drinkers are hangover resistant while others are hangover sensitive.  Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *.
Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.415). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *.
Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.161). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.404). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.123). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.   Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.131). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.102). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.102). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. No significant differences (at the same timepoint) between the hangover-resistant group and the hangoversensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.873). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.448). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.448). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *.
Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.163). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.448). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.448). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.  Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.065). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. No significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.996). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.929). Therefore, no paired comparisons were conducted (indicated by −). No significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) were found. Abbreviations: R = hangover-resistant group, S = hangover-sensitive group. Mean and standard deviation (SD) are shown. Significant differences (at the same timepoint) between the control day and the alcohol day (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by *. For the hangover-resistant group, the main effect of control vs. alcohol day was not significant (p = 0.108). Therefore, no paired comparisons were conducted (indicated by −). Significant differences (at the same timepoint) between the hangover-resistant group and the hangover-sensitive group (p < 0.0071, after Bonferroni's correction for multiple comparisons) are indicated by ‡ . Abbreviations: R = hangover-resistant group, S = hangover-sensitive group.    Figure A3. Predictors of overall hangover severity at different timepoints in the afternoon. Figure A3. Predictors of overall hangover severity at different timepoints in the afternoon.