2 persist in driving while hungover (Verster et al., 2014b). Given its costs and negative consequences, the need for an effective hangover treatment is evident (Verster, 2012). It is a persistent popular believe that the absence of an effective hangover cure helps prevent drinkers from consuming even more alcohol than they do already. According to this viewpoint, drinking in moderation is currently the only effective way to prevent hangover, and this helps many drinkers limit excessive alcohol use. Unfortunately, this popular belief has also been adopted by many physicians and researchers. In this context, researchers have suggested that having no hangovers can be a gateway to alcohol dependence or abuse (Rohsenow et al., 2012). It could then be hypothesized that if drinkers experi- ence less hangover symptoms they might drink more alcohol. However, this is not supported by a recent study that found hangover severity not to be signifi- cantly correlated to the amount of alcohol consumed or the achieved estimated peak blood alcohol concen- tration (BAC) (Hogewoning et al., 2016). Moreover, Huntley et al. (2015) examined the consequences of having a hangover for drinking on future occasions. They showed that more severe hangovers did not pre- dict the likelihood of not drinking later that day. However, they did find that the quantity of alcohol consumed on that occasion was lower than usual con- sumption levels. Other researchers reported that having hangovers does not prevent drinkers from consuming the same amounts of alcohol on future drinking occa- sions (Mallett et al., 2006). Taken together, the severity of intoxication or hang- over effects seems unrelated to the actual amount of alcohol consumed. Up to now, however, no research has directly investigated if drinkers would consume more alcohol if there was an effective and affordable hangover treatment. Given the lack of scientific data on the implications of developing an effective hangover treatment, the current study investigated whether drinkers who experience hangovers would (a) be willing to buy an effective hang- over treatment and (b) whether using such a product would affect the amount of alcohol they consume. Methods In December 2016, an online survey was held among Dutch students, 18-30 years old. The survey was designed using www.surveymonkey.com and advertised via www.facebook.com. Online informed consent was obtained from all participants; no formal ethics approval was required to conduct this research, accord- ing to the Central Committee on Research Involving Human Subjects (CCMO). As a reward for participat- ing, subjects could win a 100 Euro gift voucher. Data Drug Science, Policy and Law 0(0) collection was conducted by NeuroClinics, and funded by Sen-Jam Pharmaceutical. Unrestricted use of the data was granted to the authors. Demographic data on age, gender, and weight were collected. Weekly alcohol consumption was recorded, and the number of alcoholic drinks they consumed the day before their latest past-month hangover. Using a modified Widmark formula, taking into account gender and drinking time, the estimated peak BAC was calculated (Watson et al., 1981). Overall hangover severity (i.e. a single one-item rating) and the severity of 22 individual symptoms were rated on an 11-point scale ranging from 0 (absent) to 10 (extreme) (Hogewoning et al., 2016). Subjects were asked whether they would buy an effective hangover treatment if it was available. The answering possibilities where "yes", "no", and "don't know", and a text box was provided to leave com- ments. Subjects were divided into three groups ("yes", "no", and "don't know") according to their answer on the question whether they would buy an effective hang- over product, and alcohol consumption-related vari- ables were compared using nonparametric statistics. Next, subjects were asked whether they would con- sume more alcohol if an effective hangover treatment was available. Again, the answering possibilities where "yes", "no", and "don't know", and a text box was provided to leave comments. Subjects were divided into three groups ("yes", "no", and "don't know") according to their answer on the question whether they would consume more alcohol. Alcohol consump- tion-related variables of these three groups were com- pared using nonparametric statistics. In a follow-up survey, conducted one week after the first survey, those subjects who left their email address were contacted again and specifically asked via an open-ended question to explain why they answered "yes", "no", or "don't know" to the two questions posed in the first survey, i.e. (1) whether they would buy an effective hangover treatment if it was available and (2) whether they would consume more alcohol if an effective hangover treatment was available. Statistical analysis Only those subjects aged 18 to 30 years old who reported having a past-month hangover were included in the analyses. Statistical analyses were conducted with SPSS, version 24. For demographic variables and hangover severity scores, mean and standard deviation were computed. Using Independent Samples Mann-Whitney U tests, these variables we compared between those who would buy an effective hangover cure, those who do not know, and those who would not buy an effective Article 7 An effective hangover treatment: Friend or foe? Marlou Mackus', Marith van Schrojenstein Lantman', Aurora JAE van de Loo, David Nutt and Joris C Verster Independent Scientific Committee on Drugs Drug Science, Policy and Law Volume 3: 1-7 CC BY NC The Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2050324517741038 journals.sagepub.com/home/dsp SSAGE 2 Abstract Background: The purpose of this study was to examine whether drinkers would change their alcohol consumption behavior if an effective hangover treatment became available. Methods: An online survey was held among Dutch students, aged 18-30 years, who recently had a hangover. Participants were asked (1) whether they would buy an effective hangover treatment if it became available and (2) whether using such a product would increase their alcohol consumption. In a follow-up survey, the same partici- pants could clarify their answers in detail. Results: A total of 1837 subjects completed the survey: 69.9% of the participants indicated they would buy an effective hangover treatment if available, 8.1% answered no, and 22.1% did not know. Only 13.4% stated that using such a treatment would increase their alcohol consumption. The majority of 71.6% stated it would not increase their alcohol consumption and 15.1% did not know. The follow-up survey was completed by N=471 participants, of which 11.9% stated consuming more alcohol, 70.3% reported not to drink more alcohol, and 17.8% did not know. Motives for not consuming more alcohol were "The risk of having a hangover does not influence my drinking behavior" (24.2%), and "alcohol is a harmful substance (20.3%). Discussion: Social drinkers second the need for an effective hangover treatment. However, according to the vast majority of them, the availability of an effective hangover treatment would not result in an increase of alcohol consumption. Keywords alcohol, cure, hangover, treatment Introduction Lack of research attention for the alcohol hangover has resulted in the current absence of understanding of the pathology of the alcohol hangover and the lack of an effective treatment. Reviews note that the effective- ness of the majority of hangover treatments that are marketed has not been scientifically investigated. Those treatments that have been examined show no or little effectiveness, and the quality of most of these clin- ical trials have been criticized (Stephens et al., 2014; Verster and Penning, 2010). Although some products have been shown to bring relieve to certain hangover symptoms (e.g. reduce headache), other symptoms are not alleviated. Hence, still today the only effective way to prevent a hangover is to consume alcohol in moderation. As the costs of hangovers are largely underesti- mated, policy makers and health care campaigns have not drawn much attention to the alcohol hangover. The few studies that did try to calculate the socio-economic costs of hangovers revealed that billions of dollars glo- bally are lost annually due to absenteeism, reduced productivity, and increased risk of injury (Frone, 2006; Gjerde et al., 2010; Kim et al., 2010; Roche et al., 2016, 2008). Recent studies also showed that although during the hangover state driving is signifi- cantly impaired (Verster et al., 2014a), yet most drivers 'Division of Pharmacology, Utrecht University, The Netherlands 2Division of Pharmacology, Utrecht University, The Netherlands; Institute for Risk Assessment Sciences (IRAS), Utrecht University, The Netherlands Department of Psychiatry, Imperial College London, UK *Division of Pharmacology, Utrecht University, The Netherlands; Institute for Risk Assessment Sciences (IRAS), Utrecht University, The Netherlands; Centre for Human Psychopharmacology, Swinburne University, Australia Corresponding author: Joris C Verster, Division of Pharmacology, Utrecht University, Universiteitsweg 99, Utrecht 3584 CG, The Netherlands. Email: j.c.verster@uu.nl Drug Science, Policy and Law 0(0) 6 interested in using such a product, at the same time they attest that using it will not increase their alcohol consumption. From the analysis it became clear that the risk of having a hangover does not appear to influence drink- ing behavior. Drinkers did, however, attest that they were not planning to increase their alcohol consump- tion as alcohol is a harmful substance and they do not want to become more drunk than they already are when drinking. Alcohol consumption is viewed as part of a social gathering and has the purpose to have a good time. Hence, most drinkers are happy with the current amount of alcohol they consume and have no reason to increase this amount. In contrast, those who state that a hangover cure might make them drink more alcohol explained their decision by the fact that they currently moderate their alcohol consumption to prevent having a hangover, including the risk of reduced productivity. This idea is supported by drinkers who are unsure about the effect on their drinking behavior who stated that an effective hangover cure would make it tempting to increase their alcohol consumption. Although one can argue that it is a minority of drinkers who held these views, they still represent a substantial number of drinkers. When looking at the amount of alcohol consumed prior to their latest hangover, all groups (hangover cure buyers versus non-buyers and users versus non-users) show comparable alcohol consumption levels (around 12 units, reaching an estimated peak BACs around 0.19%) that are significantly unhealthy. In terms of prevention and education, this type of heavy alcohol use deserves attention per se. The findings of this study are supported by a recent naturalistic study (Hogewoning et al., 2016) where similar amounts of alcohol were consumed resulting in a comparable esti- mated peak BAC. In general, for health reasons mod- eration of alcohol consumption should be advocated, and plans to further increase alcohol consumption should be discouraged. The study has several limitations that need to be addressed. First, the sample that completed the survey were young volunteers, aged 18 to 30 years old. While this is a population that is overrepresented in those indulging in heavy drinking and experiencing hang- overs, it is not known from the current data if older adults and elderly drinkers would have similar views. Second, as we asked for respondents' intentions regard- ing future behavior, the current data does not prove that this behavior would actually materialize. In this context it should be noted that the intentions of our respondents contrasted with the observation made by Huntley et al. (2015) who found reduced alcohol intake the day after having a severe hangover. To further investigate the potential protective effects of having Drug Science, Policy and Law 0(0) hangovers with regard to future alcohol intake, pro- spective studies should be conducted to demonstrate that the use of an effective hangover treatment would indeed not affect drinking behavior of the vast majority of social drinkers. Finally, the data clearly show there is an interest for an effective hangover treatment. The most mentioned motives to buy such a product were to prevent experi- encing hangover symptoms and to increase productiv- ity the day after heavy alcohol consumption. Only 5% of participants chose the option to prefer consuming less alcohol as alternative means to prevent the alcohol hangover and its functional consequences. Those who said they would to buy a hangover treatment do not differ in alcohol consumption or hangover experience from those who were not interested in buying a hang- over treatment. The latter implies that other factors than alcohol consumption are important when making this decision. In this regard, the willingness of drinkers to use chemical or synthetic products as opposed to natural products, pricing, and whether pos- sible adverse effects of using the product are known and its safety is proven were mentioned as relevant. Declaration of conflicting interests Joris Verster has received grants/research support from the Dutch Ministry of infrastructure and the Environment, Janssen Research and Development, Nutricia, Red Bull, Sequential, and Takeda. He has acted as a consultant for the Canadian Beverage Association, Centraal Bureau Drogisterijbedrijven, Coleman Frost, Danone, Deenox, Eisai, Janssen, Jazz, Purdue, Red Bull, Sanofi-Aventis, Sen- Jam Pharmaceutical, Sepracor, Takeda, Transcept, Trimbos Institute, and Vital Beverages. The other authors have no potential conflicts of interest to disclose. References Frone MR (2006) Prevalence and distribution of alcohol use and impairment in the workplace: A U.S. national survey. Journal of Studies on Alcohol 67: 147156. Gjerde H, Christophersen AS, Moan IS, et al. (2010) Use of alcohol and drugs by Norwegian employees: A pilot study using questionnaires and analysis of oral fluid. Journal of Occupational Medicine and Toxicology 5: 13. Hogewoning A, Van de Loo AJAE, Mackus M, et al. (2016) Characteristics of social drinkers with and without a hang- over after heavy alcohol consumption. Substance Abuse and Rehabilitation 7: 161167. Huntley G, Treloar H, Blanchard A, et al. (2015) An event- level investigation of hangovers' relationship to age and drinking. Experimental and Clinical Psychopharmacology 23: 314-323. Kim J, Chung W, Lee S, et al. (2010) Estimating the socio- economic costs of alcohol drinking among adolescents in Korea. Journal of Preventive Medicine and Public Health 43: 341-351. Mackus et al 7 50.0 4 Drug Science, Policy and Law 0(0) Table 2. Characteristics of drinkers who would buy an effective hangover treatment, non-buyers, and those who don't know Number (%) of respondents % Men Would not buy an effective hangover treatment (C) 148 (8.1%) 47.4 Would buy an effective hangover treatment (A) Don't know (B) 1284 (69.9%) 20.7 (2.3) 405 (22.0%) 61.5 21.1 (2.4) 21.0 (2.4) Age Number of alcoholic drinks per week 13.8 (10.0) 12.4 (9.6) 14.5 (11.1)a Number of alcoholic drinks before latest hangover 12.6 (5.4) 12.2 (5.4) 13.4 (6.7)a,b 0.19 (0.1) 0.18 (0.09)a 0.20 (0.1)a,b Estimated peak BAC (%) Overall hangover severity 6.4 (1.8) 5.8 (1.8) 5.0 (2.2)a,b 7.0 (2.3) 6.7 (2.3) 6.1 (2.7)a,b Tired 6.7 (2.4) 6.3 (2.4) 5.6 (2.9)a,b Sleepiness 6.7 (2.6) 6.3 (2.7)a 5.9 (2.1)b Thirst 6.2 (2.6) 6.0 (2.4) 5.1 (2.9)a,b Concentration problems 5.4 (2.8) 5.0 (2.7) 4.4 (3.1)a,b Headache 5.2 (3.0) 4.3 (3.0) 3.6 (3.1)a,b Nausea 5.1 (3.1) 4.3 (3.1) 3.6 (3.2)a,b Apathy 5.0 (2.8) 4.4 (2.8) 3.3 (2.8)a,b Weakness 4.3 (2.9) 3.8 (3.0) 2.8 (2.9) a,b Clumsy 4.3 (3.3) 3.8 (3.2) 3.1 (3.2)a,b Reduced appetite 3.5 (3.2) 2.8 (2.7) 2.7 (3.2) Regret 3.3 (3.0) 2.5 (2.7) 2.1 (2.7)a,b Dizziness 3.0 (3.0) 2.4 (2.7) 1.9 (2.6) a,b Stomach pain 3.0 (2.9) 2.6 (2.8) 2.2 (2.8)a,b Sweating 2.6 (2.8) 2.3 (2.7) 1.7 (2.7)a,b Sensitivity to light 2.5 (2.8) 1.9 (2.6) 1.7 (2.6)b Confusion 2.4 (2.9) 1.9 (2.6) 1.5 (2.5) a,b Heart racing 2.3 (2.9) 2.1 (2.7) 1.4 (2.5) a,b Shivering 1.9 (2.6) 1.5 (2.4) 1.3 (2.4)b Heart pounding 1.6 (3.0) 1.0 (2.5)a 1.4 (2.8) Vomiting 1.4 (2.4) 1.1 (2.0) 1.1 (2.5)b Depression 0.8 (1.9) 0.6 (1.5) 0.6 (1.8) Anxiety BAC: blood alcohol concentration. "Significantly different (p < 0.05, Independent Samples Mann-Whitney U test) from B. Significantly different (p < 0.05, Independent Samples Mann-Whitney U test) from A. No significant difference in overall hangover severity was found between groups categorized with regard to whether an effective hangover product would increase their alcohol consumption. Also, severity of the major- ity of hangover symptoms did not differ between those who reported that they would consume more alcohol and those who do not. An invitation to take part in a follow-up survey was send to N=950 of the participants (those who provided their email in the original survey). Approximately half of them completed the follow-up survey (N=471, 49.6%). Of these, N=56 (11.9%) reported they would consume more alcohol if an effective hangover treatment was available, N = 331 (70.3%) reported they would not drink more alcohol, and N = 84 (17.8%) did not know. The responses given by the follow-up sample to the two questions did not differ significantly with the answer distribution, gender, or age of the original full sample that was surveyed. These participants were specifically asked why they would or would not con- sume more alcohol when an effective hangover treat- ment was available. Primary motives for consuming more alcohol if an effective treatment was available were "I currently drink less alcohol because of the risk of having an alcohol hangover" (57.8%) and "I currently drink less Mackus et al. hangover cure. Using the same test, these variables were also compared between those who state they would consume more alcohol when an effective hangover treatment was available, those who do not know, and those who state that they would not consume more alcohol. Results A total of 1837 subjects (50.4% men) who reported having had an alcohol hangover recently completed the survey. Their mean (SD) age was 20.8 (2.3) years old, and they reported consuming 13.6 (10.1) alcoholic beverages per week. Over a mean (SD) time period of 5.8 (2.0) hours of alcohol consumption, they reported consuming 12.6 (5.5) alcoholic drinks on the day before their latest alcohol hangover, which resulted in an esti- mated peak BAC of 0.19 (0.1)%. Mean (SD) overall hangover severity was 6.1 (1.9). The presence and sever- ity of individual hangover symptoms is summarized in Table 1. Would you buy it? When asked whether drinkers would buy an effective hangover treatment was available, 69.9% answered yes. A minority of 8.1% answered no and 22.0% did not Table I. Presence and severity of alcohol hangover symptoms. Reported by (%) Overall hangover severity 100.0 Tired 98.3 Sleepiness 97.1 Mean (SD) severity score 6.1 (1.9) 6.9 (2.3) 6.5 (2.4) Thirst 96.0 6.5 (2.6) Concentration problems 95.7 6.0 (2.6) Headache 92.8 5.3 (2.8) Nausea 88.0 4.9 (3.1) Apathy 82.3 4.8 (3.2) Weakness 86.7 4.7 (2.9) Clumsy 80.8 Reduced appetite 73.0 4.1 (3.0) 4.1 (3.3) Regret 71.1 3.3 (3.1) Dizziness 68.5 3.0 (2.9) Sweating 63.2 2.8 (2.9) Stomach pain 62.0 2.8 (2.9) Sensitivity to light 59.4 2.5 (2.8) Confusion 54.7 2.3 (2.8) Heart racing 51.6 2.2 (2.8) 3 know. Demographics and hangover characteristics of the three groups are summarized in Table 2. The analyses revealed that buyers do not signifi- cantly differ from non-buyers on weekly alcohol con- sumption or the amount of alcohol consumed the day before their latest hangover. However, buyers do report a significantly higher overall hangover sever- ity score when compared to non-buyers. Except for vomiting and anxiety, buyers also score significantly higher on each of the individual hangover symptom severity scores. Most commonly reported motives for buying an effective hangover treatment were I suffer from severe hangovers, so this product is welcome" (40.5%) and "it may help to be productive the day after drinking" (24.8%). Most commonly reported motives for not buying an effective hangover treatment were "the hangover is a part of the drinking experience. I have to bear the consequences" (23.6%), I am afraid I would drink more alcohol/the hangover prevents me from drinking more alcohol" (21.8%), "I do not suffer that much from hangovers" (15.5%), and "I do not want to use chemical/synthetic products, only natural treatments (12.7%). Those who did not made a choice stated "would only use it if adverse effects are known and safety proven (32.2%), if the price of the product is reasonable" (13.6%), and "I would only use it if the product consists of natural ingredients" (12.7%). As these motives were voluntarily listed in a comment box and not specifically asked for, the percentages should be interpreted as illustrative only. Impact on alcohol consumption When asked whether drinkers would consume more alcohol if an effective hangover treatment was available only 13.4% answered yes. The vast majority answered "no" (71.6%) and 15.1% did not know. A comparison between these three groups regarding demographics, drinking characteristics, and hangover experience is summarized in Table 3. Drinkers who answered "yes" consumed signifi- cantly less alcohol during the latest hangover session when compared to drinkers who said "no" to the ques- tion whether an effective hangover treatment would increase their alcohol consumption (p=0.03, 12.1 versus 12.8 alcoholic drinks). Alternatively, drinkers who answered "yes" report significantly more weekly alcohol consumption when compared to drinkers who said "no" to the question whether an effective hangover treatment would increase their alcohol consumption (p=0.05, 14.1 versus 13.7 alcoholic drinks). As the dif- ferences are less than one alcoholic drink (-0.7 and +0.5 drink, respectively), the relevance of these differ- ences is unclear. Mackus et al. Table 3. Characteristics of drinkers who would consume more alcohol if an effective hangover treatment was available, those who don't and those who don't know Would not consume more Would consume more alcohol (A) Don't know (B) 245 (13.4%) Number (%) of respondents % Men 46.5 277 (15.1%) 51.1 alcohol (C) 1313 (71.5%) 50.2 20.6 (2.1) 20.7 (2.3) 20.9 (2.4) Age 12.6 14.1 Number of alcoholic drinks per week 13.7 12.8a 11.8 Number of alcoholic drinks before latest hangover 12.1 0.19 (0.1) 0.18 (0.1) 0.19 (0.1) Estimated peak BAC (%) 6.3 (1.8) 6.2 (1.8) 6.1 (1.9) Overall hangover severity 7.1 (2.2) 7.1 (2.4) 6.8 (2.3)a,b Tired 6.7 (2.4) 6.8 (2.4) 6.4 (2.5) Sleepiness 6.6 (2.6) 6.6 (2.5) 6.5 (2.7) Thirst 6.3 (2.5) 6.2 (2.5) 6.0 (1.6) Concentration problems 5.3 (3.0) 5.1 (3.1) 4.6 (3.2)a,b Apathy 5.2 (3.0) 5.2 (3.1) 4.8 (3.0) Nausea 5.1 (2.8) 5.0 (2.7) 4.6 (2.9)b Weakness 5.1 (2.9) 5.5 (2.7) 5.3 (2.8) Headache 4.3 (3.0) 4.6 (2.8) 4.0 (3.0) Clumsy 4.1 (3.3) 4.4 (3.2) 4.0 (3.3) Reduced appetite 3.5 (3.2) 4.1 (3.2) 3.0 (3.0) Regret 3.2 (2.9) 3.5 (3.0) 2.9 (2.9) Dizziness 3.0 (3.1) 3.3 (2.9) 2.7 (2.9) Sweating 2.9 (3.0) 2.9 (2.9) 2.8 (2.9) Stomach pain 2.5 (2.9) 2.4 (2.6) 2.1 (2.8) a,b Heart racing 2.5 (2.7) 2.7 (2.7) 2.4 (2.8) Sensitivity to light 2.4 (3.0) 2.7 (2.8) 2.2 (2.7) Confusion 2.2 (2.9) 2.4 (2.8) 2.1 (2.8) Shivering 2.0 (2.7) 2.0 (2.6) 1.6 (2.5)a,b Heart pounding 1.9 (3.1) 1.4 (2.9) 1.4 (2.9)b Vomiting 1.8 (2.7) 1.8 (2.6) Depression 0.9 (1.8) 1.1 (2.1) 1.1 (2.2)a,b 0.6 (1.7)a,b Anxiety 6 BAC: blood alcohol concentration. Significantly different (p < 0.05, Independent Samples Mann-Whitney U test) from A. bSignificantly different (p < 0.05, Independent Samples Mann-Whitney U test) from B. alcohol because the hangover reduces my productivity (28.9%). For those stating not to consume more alco- hol, main reasons were "The risk of having a hangover does not influence my drinking behavior" (24.2%), "alcohol is a harmful substance" (20.3%), "I do not want to become more drunk than I already am when drinking" (18.2%), "I can not consume more alcohol than I already do" (11.7%), "I consume alcohol to have a good time, so no reason to increase the amount (10.9%), and "I am happy with the amount of alcohol I currently consume" (7.8%). Those who do not know if an effective hangover treatment will affect their drink- ing behavior stated to be not sure because "alcohol is harmful" (22.2%), it is tempting to drink more alco- hol if there are no negative consequences" (18.3%), and "because the hangover prevents excessive alcohol con- sumption (15.1%). Discussion One of the ongoing concerns, regarding potential effect- ive hangover treatment is the idea that drinkers may increase their alcohol consumption once such a product becomes available. The current study reveals, however, that this concern may be unjustified. Although the vast majority of social drinkers confirm that they are Drug Science, Policy and Law 0(0)