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Mechanisms and Mediators

Robert Swift, M.D., Ph.D.; and Dena Davidson, Ph.D.

Hangovers are a frequent, though unpleasant, experience among people who to intoxication. Despite the prevalence of , however, this condition is not well understood scientifically. Multiple possible contributors to the hangover state have been investigated, and researchers have produced evidence that alcohol can directly promote hangover symptoms through its effects on urine production, the gastrointestinal tract, blood concentrations, sleep patterns, and biological rhythms. In addition, researchers postulate that effects related to alcohol’s absence after a drinking bout (i.e., withdrawal), alcohol , and other factors (e.g., biologically active, nonalcohol compounds in beverages; the use of other drugs; certain personality traits; and a family history of ) also may contribute to the hangover condition. Few of the treatments commonly described for hangover have undergone scientific evaluation. KEY WORDS: post AOD intoxication state; symptom; urinalysis; gastrointestinal disorder; hypoglycemia; sleep disorder; circadian rhythm; metabolite; disorder of fluid or or acid-base balance; nutrient intake; ; ; neurotransmitter receptors; congenors; multiple drug use; personality trait; family AODU (alcohol and other drug use) history; drug therapy; literature review

“My first return of sense or recol- he British writer William Hickey its aftereffects, or a combination of lection was upon waking in a wrote these words in the year both. Similarly, investigators are uncer- strange, dismal-looking room, my T1768, vividly describing the tain about the degree to which hangover head aching horridly, pains of a aftermath of a bout of heavy alcohol affects a person’s thinking and mentally violent nature in every limb, and drinking—an experience commonly controlled motor functions, a question deadly sickness at the stomach. referred to as a “hangover.” Similar with serious implications for activities From the latter I was in some descriptions of hangovers appear in the degree relieved by a very copious writings of ancient Egypt and Greece vomiting. Getting out of bed, I as well as in the Old Testament. No ROBERT SWIFT, M.D., PH.D., is associate looked out of the only window in doubt, prehistoric people also experi- professor in the Department of the room, but saw nothing but enced hangovers soon after they and Human Behavior at Brown Univer- the backs of old houses, from discovered alcohol. sity, Providence, Rhode Island, and which various miserable emblems Despite its long history, however, associate chief of staff for research and of poverty were displayed . . . . At hangover has received relatively scant education at Providence Veterans that moment I do not believe in formal attention from researchers. Affairs Medical Center. the world there existed a more Little is known about the wretched creature than myself. underlying the hangover condition. For DENA DAVIDSON, PH.D., is assistant I passed some moments in a example, it is unclear whether hangover professor of psychiatry at Indiana state little short of despair . . . .” are attributable University of Medicine, Indianapolis, —William Hickey (Spenser 1913) to alcohol’s direct effects on the body, Indiana.

54 Alcohol Health & Research World Alcohol Hangover

such as job performance and driving. toms include ; a sense of the zero were tested following alcohol In addition, researchers know little room spinning (i.e., vertigo); and intoxication with peak BAC’s in the about hangover prevention and treat- possible cognitive and mood distur- range of 50 to 100 milligrams per ment. Although folk remedies for bances, especially , , deciliter (mg/dL), most of them did hangovers abound, their efficacy in and . The particular set of not show significant impairments in reducing the intensity and duration symptoms experienced and their inten- the performance of simple mental of a hangover has not received system- sity may vary from person to person tasks, such as reaction time (Lemon et atic study. In fact, some researchers and from occasion to occasion. In al. 1993). Similarly, several studies and clinicians question whether finding addition, hangover characteristics may that investigated the hangover effects an effective treatment for hangovers depend on the type of alcoholic beverage on a more complex mental task (i.e., is desirable, given that the hangover consumed and the amount a person simulated automobile driving) did not experience may deter some people . Typically, a hangover begins report impaired performance (Streufert from engaging in subsequent episodes within several hours after the cessation et al. 1995; Tornros and Laurell 1991). of heavy drinking. of drinking, when a person’s blood In contrast, a study of military pilots Although gaps clearly remain in alcohol concentration (BAC) is falling. completing a simulated flying task scientific knowledge about hangovers, Symptoms usually peak about the revealed significant decrements in research has elucidated several aspects. time BAC is zero and may continue some performance measures (particu- This article describes what is known for up to 24 hours thereafter. larly among older pilots) 8 to 14 hours about the hangover condition, the Overlap exists between hangover and after they had consumed enough alco- possible physiological factors contribut- the symptoms of mild alcohol with- hol to be considered legally drunk ing to it, and treatment options. drawal (AW), leading to the assertion (Yesavage and Leirer 1986). that hangover is a manifestation of mild withdrawal. Hangovers, how- What Is a Hangover? ever, may occur after a single bout of Prevalence of Hangover drinking, whereas withdrawal occurs A hangover is characterized by the usually after multiple, repeated bouts. Generally, the greater the amount constellation of unpleasant physical Other differences between hangover and duration of alcohol consumption, and mental symptoms that occur after and AW include a shorter period of the more prevalent is the hangover, a bout of heavy alcohol drinking (see impairment (i.e., hours for hangover although some people report experi- table 1). Physical symptoms of a versus several days for withdrawal) encing a hangover after drinking low hangover include , headache, and a lack of hallucinations and seizures levels of alcohol (i.e., one to three increased sensitivity to light and in hangover. alcoholic drinks), and some heavy sound, redness of the eyes, muscle People experiencing a hangover feel drinkers do not report experiencing aches, and thirst. Signs of increased ill and impaired. Although a hangover hangovers at all. A survey by Harburg sympathetic nervous system activity may impair task performance and and colleagues (1993) on the preva- can accompany a hangover, including thereby increase the risk of injury, lence of hangovers found that approx- increased systolic blood pressure, equivocal data exist on whether hang- imately 75 percent of the subjects rapid heartbeat (i.e., tachycardia), over actually impairs complex mental who drank to intoxication reported tremor, and sweating. Mental symp- tasks. When subjects with a BAC of experiencing a hangover at least some of the time. In a study of 2,160 Finnish men, researchers found an association Table 1 Symptoms of Hangover between increased weekly alcohol consumption and the frequency of Class of Symptoms Type hangover: 43.8 percent of the group of heaviest drinkers (i.e., study subjects Constitutional Fatigue, weakness, and thirst who drank more than 106 grams [g] Pain Headache and muscle aches of alcohol per week or approximately Gastrointestinal , vomiting, and stomach pain 9 drinks) reported experiencing a hang- Sleep and biological rhythms Decreased sleep, decreased REM,1 over monthly or more often, compared and increased slow-wave sleep with 6.6 percent of the remaining Sensory Vertigo and sensitivity to light and sound study subjects (Kauhanen et al. 1997). Cognitive Decreased attention and concentration Mood Depression, anxiety, and irritability Similarly, in a study of 1,041 drinkers Sympathetic hyperactivity Tremor, sweating, and increased pulse in New York State, 50 percent of the and systolic blood pressure subjects who drank two or more drinks per day reported experiencing hang- 1REM = rapid eye movements. overs in the previous year, whereas subjects who consumed lower levels

Vol. 22, No. 1, 1998 55 of alcohol reported fewer hangovers (i.e., antidiuretic hormone, these factors can result in the upper (Smith and Barnes 1983). Other reports, or vasopressin) from the pituitary gland. abdominal pain, nausea, and vomiting however, claim that hangovers occur In turn, reduced levels of antidiuretic experienced during a hangover. less often in heavy drinkers. In a study hormone prevent the kidneys from of 43 alcoholic drinkers admitted for reabsorbing (i.e., conserving) water Low Blood Sugar. Several alterations inpatient treatment, 50 percent of the and thereby increase urine production. in the metabolic state of the and subjects reported experiencing no hang- Additional mechanisms must be at other organs occur in response to the overs within the previous year and 23 work to increase urine production, presence of alcohol in the body and percent reported never experiencing a however, because antidiuretic hormone can result in low blood sugar levels hangover (Pristach et al. 1983). levels increase as BAC levels decline to (i.e., low levels, or hypoglycemia) zero during hangover (Eisenhofer et al. (National Institute on 1985). Sweating, vomiting, and and Alcoholism 1994). Alcohol metab- Physiological Factors also commonly occur during a hang- olism leads to fatty liver (described Contributing to Hangover over, and these conditions can result in earlier) and a buildup of an intermediate additional fluid loss and electrolyte metabolic product, lactic acid, in body Hangover symptoms have been imbalances. Symptoms of mild to mod- fluids (i.e., ). Both of these attributed to several causes (see table erate include thirst, weak- effects can inhibit glucose production. 2), including the direct physiological ness, of mucous membranes, Alcohol-induced hypoglycemia effects of alcohol on the brain and dizziness, and lightheadedness— all generally occurs after other organs; the effects of the removal commonly observed during a hangover. over several days in alcoholics who have of alcohol from these organs after alco- not been eating. In such a situation, hol exposure (i.e., withdrawal); the Gastrointestinal Disturbances. Alcohol prolonged alcohol consumption, cou- physiological effects of compounds directly irritates the stomach and pled with poor nutritional intake, not produced as a result of alcohol’s intestines, causing inflammation of only decreases glucose production but metabolism (i.e., metabolites), espe- the stomach lining (i.e., ) and also exhausts the reserves of glucose cially ; and nonalcohol delayed stomach emptying, especially stored in the liver in the form of glyco- factors, such as the toxic effects of when beverages with a high alcohol gen, thereby leading to hypoglycemia. other biologically active chemicals (i.e., concentration (i.e., greater than 15 Because glucose is the primary energy congeners) in the beverage, behaviors percent) are consumed (Lieber 1995). source of the brain, hypoglycemia can associated with the alcohol-drinking High levels of alcohol consumption contribute to hangover symptoms bout (e.g., other drug use, restricted also can produce fatty liver, an accu- such as fatigue, weakness, and mood food intake, and disruption of normal mulation of fat compounds called disturbances. Diabetics are particularly sleep time), and certain personal char- and their components sensitive to the alcohol-induced alter- acteristics (e.g., temperament, person- (i.e., free fatty acids) in liver cells. In ations in blood glucose. However, it ality, and family history of alcoholism). addition, alcohol increases the produc- has not been documented whether Although current evidence suggests that tion of gastric acid as well as pancreatic low blood sugar concentrations con- more than one factor most likely con- and intestinal secretions. Any or all of tribute to hangover symptomatically. tributes to the overall hangover state, the following sections address each of the postulated causes in turn. Table 2 Possible Contributing Factors to Hangover

Direct Alcohol Effects Direct effects of alcohol ¥ Dehydration Alcohol may directly contribute to a ¥ hangover in several ways, including ¥ Gastrointestinal disturbances the following. ¥ Low blood sugar ¥ Sleep and biological rhythm disturbances

Dehydration and Electrolyte Imbal- Alcohol withdrawal ance. Alcohol causes the body to increase urinary output (i.e., it is a ). Alcohol metabolism (i.e., acetaldehyde toxicity) The consumption of 50 g of alcohol in 250 milliliters (mL) of water (i.e. approx- Nonalcohol effects imately 4 drinks) causes the elimination ¥ Compounds other than alcohol in beverages, especially of 600 to 1,000 mL (or up to 1 quart) ¥ Use of other drugs, especially of water over several hours (Montastruc ¥ Personality type 1986). Alcohol promotes urine pro- ¥ Family history for alcoholism duction by inhibiting the release of a

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Disruption of Sleep and Other the most common type of headache AW overlap considerably. The revised Biological Rhythms. Although alcohol reported (Rasmussen and Olesen 1992). Clinical Institute Withdrawal Assess- has effects that can promote results in vasodi- ment for Alcohol (CIWA-Ar) scale, an sleep onset, the fatigue experienced latation, which may induce . instrument widely used to assess the during a hangover results from alcohol’s Alcohol has effects on several neuro- severity of a withdrawal episode in disruptive effects on sleep. Alcohol- transmitters and that are alcohol-dependent patients, measures induced sleep may be of shorter duration implicated in the pathogenesis of head- 10 withdrawal-associated items: nausea and poorer quality because of rebound aches, including , , and vomiting; tremor; sweating; anxi- excitation (see the section “Effects of and (Parantainen 1983). ety; agitation; headache; disturbances Alcohol Withdrawal”) after BAC’s fall, However, the etiology of hangover in the sense of touch, hearing, and leading to insomnia (Walsh et al. 1991). headache remains unknown. vision (e.g., hallucinations); and orien- Furthermore, when drinking behavior tation (e.g., awareness of the date and takes place in the evening or at night Effects of Alcohol Withdrawal location) (Sullivan et al. 1989, see also (as it often does), it can compete with p. 8 of the article by Saitz for a sample sleep time, thereby reducing the length The AW syndrome following the of the assessment form). Several of of time a person sleeps. Alcohol also cessation of excessive drinking results these items also are usually present disrupts the normal sleep pattern, from compensatory changes in the during a hangover, including nausea decreasing the time spent in the dream- central nervous system that take place and vomiting, tremor, sweating, anxiety, ing state (i.e., rapid eye movement [REM] in response to chronically administered headache, and sensory disturbances. sleep) and increasing the time spent depressant substances (in this case, Second, Begleiter and colleagues in deep (i.e., slow-wave) sleep. In alcohol, or more specifically, ethanol). (1974) present evidence that the addition, alcohol relaxes the throat These changes include alterations in hangover condition is actually a state muscles, resulting in increased snoring two types of receptors embedded in of central nervous system excitation, and, possibly, periodic cessation of nerve cell membranes. One despite the perceived sedation and breathing (i.e., sleep apnea). type binds with an important chemi- . Support for this view comes Alcohol interferes with other biolog- cal messenger (i.e., neurotransmitter) from the research of Pinel and Mucha ical rhythms as well, and these effects called gamma-aminobutyric acid (1980), which shows that single doses persist into the hangover period. For (GABA), and the other type binds of alcohol decrease seizure thresholds example, alcohol disrupts the normal with another neurotransmitter, gluta- in animals several hours later. Their 24-hour (i.e., circadian) rhythm in body mate. Both GABA and glutamate are finding indicates rebound excitation, temperature, inducing a body temper- critical in regulating nerve cell activity: a phenomenon noted to occur after ature that is abnormally low during GABA is the body’s primary means short-term administration of some intoxication and abnormally high during of inhibiting nerve cell activity, and that can quickly clear the a hangover. Alcohol intoxication also glutamate is the primary means of body, including alcohol and certain interferes with the circadian nighttime exciting it. drugs. secretion of growth hormone, which Following chronic alcohol exposure, Third, the observation that alcohol is important in bone growth and the body decreases (i.e., downregulates) readministration alleviates the unpleas- protein synthesis. In contrast, alcohol the number or sensitivity of GABA antness of both AW syndrome and induces the release of adrenocortico- receptors and increases (i.e., upregulates) hangovers suggests that the two expe- tropic hormone from the pituitary the number or sensitivity of glutamate riences share a common process. gland, which in turn stimulates the receptors in an effort to counterbalance release of , a hormone that plays alcohol’s sedative effects. When alcohol Effects of Alcohol Metabolites a role in carbohydrate metabolism and is removed from the body, however, the stress response; alcohol thereby disrupts central nervous system and the portion Alcohol undergoes a two-step process the normal circadian rise and fall of of the nervous system that coordinates in its metabolism (see figure). First, an cortisol levels. Overall, alcohol’s disrup- response to stress (i.e., the sympathetic enzyme (i.e., alcohol ) tion of circadian rhythms induces a nervous system) remain in an unbal- metabolizes alcohol to an intermediate “jet lag” that is hypothesized to account anced “overdrive” state (Tsai et al. 1995). product, acetaldehyde; then a second for some of the deleterious effects of a Sympathetic nervous system hyperac- enzyme ( dehydrogenase hangover (Gauvin et al. 1997). tivity accounts for the tremors, sweating, [ALDH]) metabolizes acetaldehyde to and tachycardia observed in both hang- . Acetaldehyde is a chemically Alcohol and Headache over and AW syndrome. reactive substance that binds to pro- Several lines of evidence suggest that teins and other biologically important In a large epidemiological survey of a hangover is a mild manifestation of compounds. At higher concentrations, headache in Danish 25- to 64-year-olds, the AW syndrome in non-alcohol- it causes toxic effects, such as a rapid the lifetime prevalence of hangover dependent drinkers. First, the signs pulse, sweating, skin flushing, nausea, headache was 72 percent, making it and symptoms of hangover and mild and vomiting. In most people, ALDH

Vol. 22, No. 1, 1998 57 metabolizes acetaldehyde quickly and One specific implicated metabolism and thereby slow the pro- efficiently, so that this intermediate in hangover effects is methanol, which duction of and . metabolite does not accumulate in high is an alcohol compound found in Certain people develop headaches concentrations, although small amounts alcoholic beverages along with ethanol. soon after drinking red but not are present in the blood during alcohol The two compounds differ slightly in after drinking or . intoxication. In some people, however, chemical structure in that methanol Recent research finds that , but genetic variants of the ALDH enzyme contains one less carbon atom and two not white wine or vodka, can increase permit acetaldehyde to accumulate. fewer hydrogen atoms than ethanol. plasma serotonin and plasma histamine Those people routinely flush, sweat, The same enzymes that metabolize levels. The specific agents in wine and become ill after consuming small ethanol, , and responsible for these increased levels amounts of alcohol. aldehyde dehydrogenase also metabo- are not known. Increased plasma sero- Because of the similarity between lize methanol; however, the products tonin and histamine can trigger head- the acetaldehyde reaction and a hang- of methanol metabolism (i.e., formalde- aches in susceptible people (Pattichis over, some investigators have suggested hyde and formic acid) are extremely et al. 1995; Jarisch and Wantke 1996). that acetaldehyde causes hangovers. toxic and in high concentrations may Although free acetaldehyde is not pre- cause blindness and death. Use of Other Drugs. The use of other sent in the blood after BAC’s reach Support for methanol’s contribution drugs often accompanies heavy alcohol zero, the toxic effects of acetaldehyde to hangovers comes from several sources. consumption. Most heavy drinkers produced during alcohol metabolism For example, distilled spirits that are smoke cigarettes, and some also use may persist into the hangover period. more frequently associated with the marijuana, , or other drugs. development of a hangover, such as Although certain drugs can themselves and whiskeys, contain the produce hangover symptoms and affect Effects of Factors Other highest concentrations of methanol. alcohol intoxication, the effects of the Than Alcohol Moreover, in an experimental study various alcohol and other drug combina- Factors other than alcohol also may with four subjects who consumed red tions on alcohol hangover are unknown. contribute to a hangover. These factors wine containing 100 milligrams per include the following possibilities. liter (mg/L) of methanol, Jones (1987) Personal Influences. Some evidence found that elevated blood levels of exists that increased hangover symptoms Congeners. Among other reasons, methanol persisted for several hours occur more often in people possessing people consume alcoholic beverages after ethanol was metabolized, which certain personality traits, such as neu- for their ethanol content. Most alcoholic corresponded to the time course of roticism, anger, and defensiveness. beverages contain smaller amounts of hangover symptoms. Methanol lingers Negative life events and feelings of guilt other biologically active compounds, after ethanol levels drop, because ethanol about drinking also are associated with however, including other . competitively inhibits methanol metab- experiencing more hangovers (Harburg These compounds, known as congeners, olism. The fact that ethanol readmin- et al. 1993). In addition, Earleywine contribute to the , smell, and istration fends off hangover effects (1993a,b) reports greater hangover appearance of alcoholic beverages. may be further evidence of methanol’s symptoms in people who have a higher Congeners may be produced along contribution to the hangover condition, personality risk for the development of with ethanol during , given ethanol’s ability to block methanol alcoholism (as measured by the Mac- generated during aging or processing through the degradation of the bever- age’s organic components, or added Ð CH3CH2OH ADH CH3CHO ALDH CH3COO to the beverage during the production Ethanol Acetaldehyde Acetate process. Investigators now believe that congeners may contribute to a beverage’s intoxicating effects and to a subsequent hangover. Research has shown that beverages composed of more pure ethanol, such as NAD NADH NAD NADH or vodka, induce fewer hangover effects than do beverages containing a large number of congeners, such The metabolism of beverage alcohol (i.e., ethanol) by the alcohol dehydrogenase (ADH) pathway. as whiskey, , or red wine (Chapman 1970; Pawan 1973). A NOTE: ADH = alcohol dehydrogenase; ALDH = aldehyde dehydrogenase; NAD = nicotinamide adenine hangover also may occur when pure dinucleotide; NADH = reduced NAD. ethanol is administered, however.

58 Alcohol Health & Research World Alcohol Hangover

Andrew Scale [MacAndrew 1965]). Attentiveness to the quantity and enhances acetaminophen’s toxicity to Those studies suggest that people who quality of alcohol consumed can have the liver (Girre et al. 1993). have an elevated personality risk for a significant effect on preventing hang- , a beta-adrenergic alcoholism experience more acute over. Hangover symptoms are less antagonist1 used to treat high blood withdrawal and hangover symptoms likely to occur if a person drinks only pressure and headaches, re- and may initiate further drinking in an small, nonintoxicating amounts. Even duces the sympathetic hyperactivity effort to find relief. among people who drink to intoxication, of AW; however, a small, double-blind, Research has shown that a history those who consume lower amounts of placebo-controlled study did not find of alcoholism in a person’s family (i.e., alcohol appear less likely to develop a propranolol to be effective in reducing a positive family history) is associated hangover than those who drink higher hangover symptoms, including headache with a decreased sensitivity to the intox- amounts. Hangovers have not been (Bogin et al. 1987). Antagonists at the icating effects of alcohol and a greater associated with drinking beverages with serotonin-3 receptor,2 such as ondan- risk for developing alcoholism (Schuckit a low alcohol content or with drinking setron and tropisetron, are and Smith 1996). Newlin and Pretorius nonalcoholic beverages. (i.e., they control nausea and vomiting) (1990) suggested that a positive family The type of alcohol consumed also and block certain alcohol effects; how- history for alcoholism may be associated may have a significant effect on reduc- ever, a small clinical trial did not show with a tendency for increased hangover ing hangover (Chapman 1970; Pawan efficacy in alleviating hangover (Muh- symptoms as well. Their research 1973). Alcoholic beverages that contain onen et al. 1997). (often taken compared the self-reported hangover few congeners (e.g., pure ethanol, vodka, as coffee) is commonly used to counter- symptoms in college-age sons of alco- and gin) are associated with a lower act the fatigue and malaise associated holic fathers with symptoms in sons incidence of hangover than are beverages with the hangover condition. Although of nonalcoholic fathers and found that contain a number of congeners this traditional practice lacks scientific that the subjects with a positive fam- (e.g., brandy, whiskey, and red wine). support, William Hickey, quoted at the ily history for alcoholism had had Other interventions may reduce the beginning of this article, wrote that greater hangover symptoms during the intensity of a hangover but have not “very strong coffee proved of infinite previous year. The amount of drink- been systematically studied. Consump- benefit” (Spenser 1913). ing was comparable between the two tion of fruits, fruit , or other Readministration of alcohol—the groups, although the subjects with a -containing foods is reported “ that bit you” remedy— positive family history reported con- to decrease hangover intensity, for reportedly cures a hangover, but people suming significantly more mixed example (Seppala et al. 1976). Also, experiencing a hangover should avoid drinks than the group with a negative bland foods containing complex car- further alcohol use. Additional drink- family history. bohydrates, such as toast or crackers, ing will only enhance the existing can counter low blood sugar levels in toxicity of the alcohol consumed during people subject to hypoglycemia and the previous bout and may increase the Treatments for Hangover can possibly relieve nausea. In addition, likelihood of even further drinking. adequate sleep may ease the fatigue Many treatments are described to pre- associated with , and vent hangover, shorten its duration, drinking nonalcoholic beverages during Areas for Future Study and reduce the severity of its symptoms, and after alcohol consumption may including innumerable folk remedies reduce alcohol-induced dehydration. Several topics related to hangovers and recommendations. Few treatments Certain medications may provide warrant research attention. The effect have undergone rigorous investigation, symptomatic relief for hangover symp- of congeners, especially methanol, on however. Conservative management toms. For example, may alleviate the occurrence of hangover needs closer offers the best course of treatment. nausea and gastritis. and other examination, for example. Such research Time is the most important compo- nonsteroidal anti-inflammatory medi- could help determine whether it is nent, because hangover symptoms cations (e.g., or ) ethanol or congeners that produce the will usually abate over 8 to 24 hours. may reduce the headache and muscle major signs and symptoms of hangover, aches associated with a hangover but and an answer to this key question 1An antagonist is an agent that interferes with or should be used cautiously, particularly would advance our understanding of blocks the action of another agent, disease, or if upper abdominal pain or nausea is hangover pathophysiology. structure. A beta-adrenergic antagonist blocks the present. Anti-inflammatory medications A particularly intriguing observation action of certain neurotransmitters governing the sympathetic nervous system. are themselves gastric irritants and is that people with traits associated with will compound alcohol-induced gas- an increased risk for alcoholism (e.g., 2Serotonin antagonists block the actions of tritis. Although acetaminophen is a certain personality factors or a positive serotonin, a neurotransmitter that can affect mood as well as inhibit gastric secretion and common alternative to aspirin, its use family history for alcoholism) experience stimulate smooth muscle, such as that governing should be avoided during the hangover more severe hangovers. Although logic the contractions of the digestive system. period, because alcohol metabolism dictates that enduring more severe or

Vol. 22, No. 1, 1998 59 more frequent hangovers would deter, Ten Years of Progress, New York: Plenum Press, PATTICHIS, K.; LOUCA, L.; JARMAN, J.; SANDLER, 1993. pp. 281–304. M.; AND GLOVER, V. 5-hydroxytryptamine rather than promote, further alcohol release from platelets by different red : drinking, mild AW symptoms are also GAUVIN, D.V.; BRISCOE, R.J.; BAIRD, T.J.; VALLETT, Implications for migraine. European Journal of associated with an increased craving M.; CARL, K.L.; AND HOLLOWAY, F.A. Cross- Pharmacology 292:173–177, 1995. for alcohol (Littleton and Little 1994). generalization of an EtOH “hangover” cue to endogenously and exogenously induced stimuli. PAWAN, G.L. Alcoholic drinks and hangover effects. Future investigations could focus on Pharmacology Biochemistry and Behavior 57(1/2): Proceedings of the Nutrition Society 32(1):15A, 1973. whether people can be biologically 199–206, 1997. predisposed to experience more severe PINEL, J.P.J., AND MUCHA, R.F. Increased suscep- GIRRE, C.; HISPARD, E.; PALOMBO, S.; N’GUYEN, tibility to seizures following brief exposure to AW and whether such a tendency in C.; AND DALLY, S. Increased metabolism of aceta- alcohol: Hangover or artifact. In: Eriksson, K., turn predisposes them to increased minophen in chronically alcoholic patients. ed. Animal Models in Alcohol Research. New York: alcohol consumption. Alcoholism: Clinical & Experimental Research 17(1): Academic Press, 1980. pp. 413–418. 170–173, 1993. Animal models of hangover have PRISTACH, C.A.; SMITH, C.M.; AND WHITNEY, been developed and may provide in- HARBURG, E.; GUNN, R.; GLEIBERMAN, L.; DIFRAN- R.B. Alcohol withdrawal syndromes: Prediction sights into the physiological and behav- CEISCO, W.; AND SCHORK, A. Psychosocial factors, from detailed medical and drinking histories. ioral changes that occur in the period alcohol use, and hangover signs among social Drug and 11(2):177–199, 1983. drinkers: A reappraisal. Journal of Clinical Epidemiology RASMUSSEN, B.K., AND OLESEN, J. Symptomatic immediately after intoxication (Gauvin 46(5):413–422, 1993. et al. 1993, 1997). These animal models and non-symptomatic headaches in a general could be used to explore the effects of JARISCH, R., AND WANTKE, F. Wine and headache. population. Neurology 42(6):1225–1231, 1992. International Archives of Allergy and Immunology SCHUCKIT, M.A., AND SMITH, T.L. An 8-year early withdrawal and of congeners and to 110(1):7–12, 1996. determine whether hangovers predispose follow-up of 450 sons of alcoholic and control to or deter further alcohol consumption. JONES, A.W. Elimination half-life of methanol subjects. Archives of General Psychiatry 53(3): during hangover. Pharmacology & 202–210, 1996. In summary, hangover is a complex 60(3):217–220, 1987. state that probably cannot be under- SEPPALA, T.; LEINO, T.; LINNOILA, M.; HUTTUNEN, stood by a unitary explanation. 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