Alcohol Hangover Mechanisms and Mediators

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Alcohol Hangover
                                      Mechanisms and Mediators

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

             Hangovers are a frequent, though unpleasant, experience among people who drink to
             intoxication. Despite the prevalence of hangovers, 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
             sugar 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 metabolism, and other factors (e.g., biologically active, nonalcohol compounds in
             beverages; the use of other drugs; certain personality traits; and a family history of
             alcoholism) also may contribute to the hangover condition. Few of the treatments commonly
             described for hangover have undergone scientific evaluation. K EY WORDS : post AOD
             intoxication state; symptom; urinalysis; gastrointestinal disorder; hypoglycemia; sleep
             disorder; circadian rhythm; ethanol metabolite; disorder of fluid or electrolyte or acid-base
             balance; nutrient intake; headache; vomiting; 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-
                                              T
                                                      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                 1768, 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 Psychiatry
     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 physiology
     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 . . . .”   signs and symptoms are attributable        University of Medicine, Indianapolis,
     —William Hickey (Spenser 1913)           to alcohol’s direct effects on the body,   Indiana.

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Alcohol Hangover

such as job performance and driving.           toms include dizziness; 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 depression, anxiety,     deciliter (mg/dL), most of them did
hangovers abound, their efficacy in            and irritability. 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               drinks. 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 fatigue, 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                  Nausea, 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-
   1
   REM = 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           hormone (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 liver 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 glucose levels, or hypoglycemia)
                                              zero during hangover (Eisenhofer et al.        (National Institute on Alcohol Abuse
                                              1985). Sweating, vomiting, and diarrhea        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., lactic acidosis). Both of these
attributed to several causes (see table       erate dehydration include thirst, weak-        effects can inhibit glucose production.
2), including the direct physiological        ness, dryness of mucous membranes,                 Alcohol-induced hypoglycemia
effects of alcohol on the brain and           dizziness, and lightheadedness— all            generally occurs after binge drinking
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., gastritis) and       also exhausts the reserves of glucose
cially acetaldehyde; 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-       triglycerides 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 effects of alcohol
Direct Alcohol Effects                                      • Dehydration
Alcohol may directly contribute to a                        • Electrolyte imbalance
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 diuretic).         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 methanol
of 600 to 1,000 mL (or up to 1 quart)                     • Use of other drugs, especially nicotine
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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Alcohol Hangover

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 sedative effects that can promote         Alcohol intoxication results in vasodi-       ment for Alcohol (CIWA-Ar) scale, an
sleep onset, the fatigue experienced          latation, which may induce headaches.         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 hormones 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 histamine, serotonin,        and vomiting; tremor; sweating; anxi-
excitation (see the section “Effects of       and prostaglandins (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                                                      location) (Sullivan et al. 1989, see also
(as it often does), it can compete with
                                              Effects of Alcohol Withdrawal                 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 receptor            despite the perceived sedation and
breathing (i.e., sleep apnea).                type binds with an important chemi-           malaise. 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        sedatives 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.                                  benzodiazepine 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 cortisol, a hormone that plays     alcohol’s sedative effects. When alcohol
a role in carbohydrate metabolism and         is removed from the body, however, the
                                                                                            Effects of Alcohol Metabolites
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 dehydrogenase)
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 (aldehyde dehydrogenase
hangover (Gauvin et al. 1997).                tivity accounts for the tremors, sweating,    [ALDH]) metabolizes acetaldehyde to
                                              and tachycardia observed in both hang-        acetate. Acetaldehyde is a chemically
                                              over and AW syndrome.                         reactive substance that binds to pro-
Alcohol and Headache                              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 congener implicated                  metabolism and thereby slow the pro-
efficiently, so that this intermediate      in hangover effects is methanol, which                duction of formaldehyde and formic acid.
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 wine but not
are present in the blood during alcohol     The two compounds differ slightly in                  after drinking white wine or vodka.
intoxication. In some people, however,      chemical structure in that methanol                   Recent research finds that red wine, 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, alcohol dehydrogenase, 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, cocaine, or other drugs.
                                            development of a hangover, such as                    Although certain drugs can themselves
                                            brandies 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 alcohols.          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 taste, 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 fermentation,           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
                                                    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 gin                         NAD                     NADH           NAD                       NADH
or vodka, induce fewer hangover
effects than do beverages containing
                                              The metabolism of beverage alcohol (i.e., ethanol) by the alcohol dehydrogenase
a large number of congeners, such
                                              (ADH) pathway.
as whiskey, brandy, 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-        Propranolol, 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 migraine 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 antiemetics
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). Caffeine (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 juices, or other          Readministration of alcohol—the
groups, although the subjects with a                  fructose-containing foods is reported       “hair of the dog 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 sleep deprivation, 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, antacids may alleviate   the occurrence of hangover needs closer
offers the best course of treatment.                  nausea and gastritis. Aspirin 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., ibuprofen or naproxen)       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
1
  An 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.,
2
  Serotonin 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 wines:
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.
                                                     generalization of an EtOH “hangover” cue to
for alcohol (Littleton and Little 1994).             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.
                                                                                                                 PINEL, J.P.J., AND MUCHA, R.F. Increased suscep-
predisposed to experience more severe                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.
    Animal models of hangover have                   170–173, 1993.
                                                                                                                 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.
                                                     alcohol use, and hangover signs among social                Drug and Alcohol Dependence 11(2):177–199, 1983.
ioral changes that occur in the period
                                                     drinkers: A reappraisal. Journal of Clinical Epidemiology
immediately after intoxication (Gauvin               46(5):413–422, 1993.
                                                                                                                 RASMUSSEN, B.K., AND OLESEN, J. Symptomatic
et al. 1993, 1997). These animal models                                                                          and non-symptomatic headaches in a general
                                                     JARISCH, R., AND WANTKE, F. Wine and headache.              population. Neurology 42(6):1225–1231, 1992.
could be used to explore the effects of
                                                     International Archives of Allergy and Immunology
early withdrawal and of congeners and to             110(1):7–12, 1996.
                                                                                                                 SCHUCKIT, M.A., AND SMITH, T.L. An 8-year
determine whether hangovers predispose                                                                           follow-up of 450 sons of alcoholic and control
                                                     JONES, A.W. Elimination half-life of methanol               subjects. Archives of General Psychiatry 53(3):
to or deter further alcohol consumption.                                                                         202–210, 1996.
                                                     during hangover. Pharmacology & Toxicology
    In summary, hangover is a complex                60(3):217–220, 1987.
state that probably cannot be under-                                                                             SEPPALA, T.; LEINO, T.; LINNOILA, M.; HUTTUNEN,
                                                     KAUHANEN, J.; KAPLAN, G.A.; GOLDBERG, D.D.;                 M.O.; AND YLIKAHRI, R.H. Effects of hangover
stood by a unitary explanation. Under-                                                                           on psychomotor skills related to driving: Mod-
                                                     COHEN, R.D.; LAKKA, T.A.; AND SALONEN, J.T.
standing the hangover condition, how-                Frequent hangovers and cardiovascular mortality in          ification by fructose and glucose. Acta Pharm-
ever, will lead to a better comprehension            middle-aged men. Epidemiology 8(3):310–314, 1997.           acologia Toxicologia 38:209–218, 1976.
of the physiological effects of alcohol                                                                          SMITH, C.M., AND BARNES, G.M. Signs and
                                                     LEMON, J.; CHESHER, G.; FOX, A.; GREELEY, J.;
and the adaptive responses that alco-                AND  NABKE, C. Investigation of the hangover                symptoms of hangover: Prevalence and relationship
hol engenders. ■                                     effects of an acute dose of alcohol on psychomo-            to alcohol use in a general adult population. Drug
                                                     tor performance. Alcoholism: Clinical and Exper-            and Alcohol Dependence 11(3/4):249–269, 1983.
                                                     imental Research 17(3):665–668, 1993.
                                                                                                                 SPENSER, A., ED. Memoirs of William Hickey. Lon-
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