HUMAN COFFEE DRINKING - NCBI

JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR

HUMAN COFFEE DRINKING: MANIPULATION OFCONCENTRATION AND CAFFEINE DOSE

ROLAND R. GRIFFITHS, GEORGE E. BIGELOW, IRA A. LIEBSON,MARY O'KEEFFE, DAVID O'LEARY, AND NASON Russ

THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE

In a residential research ward coffee drinking was studied in 9 volunteer human subjects withhistories of heavy coffee drinking. A series of five experiments was undertaken to characterize ad-libitum coffee consumption and to investigate the effects of manipulating coffee concentration, caffeinedose per cup, and caffeine preloads prior to coffee drinking. Manipulations were double-blind andscheduled in randomized sequences across days. When cups of coffee were freely available, coffeedrinking tended to be rather regularly spaced during the day with intercup intervals becoming pro-gressively longer throughout the day; experimental manipulations showed that this lengthening ofintercup intervals was not due to accumulating caffeine levels. Number of cups of coffee consumedwas an inverted U-shaped function of both coffee concentration and caffeine dose per cup; however,coffee-concentration and dose-per-cup manipulations did not produce similar effects on other measuresof coffee drinking (intercup interval, time to drink a cup, within-day distribution of cups). Caffeinepreload produced dose-related decreases in number of cups consumed. As a whole, these experimentsprovide some limited evidence for both the suppressive and the reinforcing effects of caffeine on coffeeconsumption. Examination of total daily coffee and caffeine intake across experiments, however,provides no evidence for precise regulation (i.e., titration) of coffee or caffeine intake.

Key uords: coffee, caffeine, drug self-administration, tremor, subjective effects, coffee drinking,humans

Caffeine is the world's most widely usedbehaviorally active drug, with one or morecaffeine-containing beverages and foods con-sumed by most adults and children. Coffeeand tea drinking account for 97% of caffeineconsumption worldwide (Gilbert, 1984). In theUnited States, average daily caffeine intakeper capita is approximately 200 mg (Gilbert,1984; Graham, 1978). Although there is littleapparent health risk associated with con-sumption of low amounts of caffeine (Dews,1982; Ernster, 1984), several investigatorshave argued that significant health risk maybegin to emerge at 500 to 600 mg of caffeineper day (Gilbert, 1976; Greden, 1981). Var-ious North American surveys suggest that asmany as 10 to 30% of adults consume morethan 500 mg of caffeine per day (Greden,1981); it is plausible, therefore, that a signif-icant proportion of the population may be athealth risk from excessive caffeine consump-tion.

This research was supported by USPHS ResearchGrants R01 DA03890 and K02 DA00050 from the Na-tional Institute on Drug Abuse. Reprint requests shouldbe sent to Roland R. Griffiths, Department of Psychiatry,623 Traylor, Johns Hopkins University School of Med-icine, Baltimore, Maryland 21205.

Because of the high prevalence of caffeineconsumption, interest in possible perfor-mance-enhancing effects of caffeine, and in-creasing concern over health risks related tocaffeine use, the effects of caffeine have been,and are continuing to be, extensively studied(Dews, 1982; Gilbert, 1976; G. A. Spiller,1984; Weiss & Laties, 1962). Surprisingly,although coffee drinking is recognized as themajor vehicle of caffeine consumption, only afew studies have experimentally addressed thedeterminants of such behavior (Bernard, Den-nehy, & Keefauver, 1981; Foxx & Rubinoff,1979; James, Stirling, & Hampton, 1985;Kozlowski, 1976). Even though it is widelybelieved and there is much circumstantial evi-dence suggesting that caffeine is the primarypharmacological constituent in coffee that isresponsible for maintaining chronic, high-vol-ume coffee consumption (Gilbert, 1976; Gre-den, 1981), an unequivocal experimentaldemonstration of the reinforcing effects of caf-feine in coffee apparently has not been pub-lished. The lack of research on coffee drinkingas an instance of drug self-administration isall the more surprising because methodologiesfor conducting human drug self-administra-tion studies have been well established and

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1986, 45, 133-148 NUMBER 2 (MARCH)

ROLAND R. GRIFFITHS et al.

Table 1

Subject characteristics and sequence of experiments.

Self- SequenceEducation: reported Self- ofGrade Years of cups reported History History exposure

Age Weight level coffee coffee cigarettes of drug of alcohol to experi-Subject (years) (kg) completed drinking per day per day abuse abuse ments

S-CI 26 68 12 10 18 40 Yes No 1, 2, 3S-PO 47 75 12+ 32 9 40 No No 1, 2, 3S-WA 43 83 5 34 24 50 No Yes 1, 2, 3S-DA 48 82 12 29 14 55 No Yes 1,4S-HA 37 66 8 22 25 25 No Yes 1, 4S-LE 49 68 12+ 31 15 35 No Yes 1, 4, 5S-KA 49 84 12 36 12 35 Yes Yes 1, 5S-TO 39 86 10 10 15 70 No Yes 1,5S-JO 29 70 12+ 15 15 50 No No 1

have been previously used to evaluate a widevariety of compounds such as ethanol, mari-huana, heroin, sedatives, and tobacco (Grif-fiths, Bigelow, & Henningfield, 1980).The present studies were undertaken to be-

gin to investigate coffee drinking as drug self-administration. Volunteers with histories ofheavy coffee drinking were paid to live in aresidential research ward where access to cof-fee and other dietary sources of caffeine couldbe experimentally controlled and manipu-lated. The basic strategy was similar to thatemployed previously in this laboratory to in-vestigate the self-administration of ethanol(Bigelow, Griffiths, & Liebson, 1975), seda-tives (Griffiths, Bigelow, & Liebson, 1976),and tobacco (Griffiths, Henningfield, & Big-elow, 1982). The primary objectives of thesestudies were to determine the feasibility of us-ing an intensive within-subject design to in-vestigate coffee drinking and to begin to ex-plore the control of coffee drinking by coffeeconcentration and caffeine.

GENERAL METHODSSubjects

Nine healthy male volunteers with historiesof heavy coffee drinking participated. Table 1shows individual subject characteristics. Allbut two of the volunteers had histories ofproblem alcohol drinking and/or drug abuse.Subjects reported consuming an average of 9to 25 cups of coffee per day. Caffeine intakefrom sources other than coffee (e.g., cola, tea,chocolate, medications) was relatively low.

Given the rough estimate of 85 mg per cup ofcoffee (Bunker & McWilliams, 1979; Gilbert,Marshman, Schwieder, & Berg, 1976), esti-mated daily caffeine intake ranged between 10to 32 mg/kg. This level of caffeine consump-tion is in the 99th percentile of adults in theUnited States (Graham, 1978). Details ofsubject screening, financial compensation, andinformed consent were similar to those de-scribed previously (Griffiths et al., 1982).Briefly, on the basis of physical examination,history, routine laboratory chemistries, andchest X-ray, participants were found to bewithout significant medical or psychiatric dis-turbance other than their drug/alcohol abuse.Volunteers were recruited from the local com-munity and paid for their participation at therate of approximately $80.00 per week; nonewas institutionalized or under legal pressureto enroll. Before research participation, sub-jects gave their sober, informed, written con-sent to the research procedure.

SettingSubjects participated while residing in an

eight-bed behavioral pharmacology researchward that provided continuous access to var-ious recreational, reading, and craft activities.Cooperation with research procedures andward routines was maintained via an earningssystem in which points, which were convert-ible to money, were earned by engaging invarious personal and ward-maintenance ac-tivities; these earnings could be spent on mi-nor ward privileges and could be sacrificed asconsequence of rule violations.

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HUMAN COFFEE DRINKING

General ProceduresAfter admission to the research ward, sub-

jects were observed for a period of 2 to 6 daysbefore the initiation of the experiments. Thesubjects participated in this research singlyrather than in groups, a procedure that in-creases the independence of each subject's data.The number of other residents in the researchward varied unsystematically between two andseven. These other residents participated indifferent behavioral pharmacology experi-ments that sometimes involved the adminis-tration of opioids, ethanol, barbiturates, orbenzodiazepines.

Other than a general explanation of exper-imental purpose (described below), subjectswere given no instruction as to what they were"supposed" to do or of what outcomes mightbe expected. To reduce the possibility thatsubjects would receive instructions or expla-nations that might confound the results, wardstaff were explicitly instructed to refrain fromdiscussing experiments with subjects, exceptto provide an objective description of the rou-tines and procedures that a subject must fol-low. Subjects received explicit instructionsconcerning details of the daily research pro-cedures and concerning the residential wardrules, including the fact that they should re-main in the ward dayroom area from 7:15a.m. to 5:00 p.m. daily except for necessarybrief visits to the bathroom.

Coffee AvailabilitySubjects were told that the general purpose

of the research was to investigate the effectsof different kinds and strengths of coffee "uponhow you feel, upon your behavior, and uponthe physiological response of your body." Theywere told that during their research partici-pation the brand, strength, and caffeine con-tent of the coffee might be changed from dayto day, but the coffee would never be changedwithin the day. With respect to caffeine, sub-jects were told that the caffeine content of thecoffee "may be varied from no caffeine at allto a high dose of caffeine (as much as 10 timesgreater than a normal cup of coffee)." It wasemphasized to subjects that they were free todrink as much or as little coffee as they de-sired.

During the experiments subjects were al-lowed to drink only coffee prepared by staff.Other sources of caffeine (e.g., cola, tea, choc-

olate, etc.) were monitored and forbidden.Each day staff members were given 20 or morepremeasured individual doses of coffee, markedonly with that day's date, for dispensing to the1 subject who was residing in the researchward at that time. Neither staff nor subjectswere informed of the coffee brand, amount ofcoffee, or the caffeine content of the premea-sured doses. Throughout the studies Taster'sChoice® freeze-dried caffeinated or decaffein-ated coffee was used. Except in Experiments2 and 3, which involved manipulation of cof-fee concentration, coffee was prepared at themanufacturer's recommended concentration of2 g freeze-dried coffee (approximately 1rounded teaspoon) per cup. This amount ofcaffeinated and decaffeinated Taster's Choice®coffee has approximately 52 and 2 mg caf-feine, respectively ("Instant Coffees," 1979).When a subject wanted coffee, he informedthe staff. Staff poured the coffee dose in a cup,added preheated water (approximately 70 °C)to a volume of 180 mL, gave the cup to thesubject, recorded the time the cup was dis-pensed, and began a timer to measure the timeto consume the coffee. Subjects were allowedto add premeasured portions of cream and/orsugar if they desired; however they were notallowed to change these amounts during thecourse of their experimental participation. Tofacilitate staff monitoring of coffee drinking,subjects were required to drink their coffeewhile sitting in a designated chair near thenurses' station. In Experiment 1, coffee wasavailable 24 hr a day; in all subsequent ex-perimients, coffee was not available during theperiod from 12 midnight until the morningprotocol began. The restriction of coffee over-night was implemented in order to eliminatethe possible sleep-disrupting effects of con-suming coffee at night. Although this changein coffee availability means that unambiguouscomparisons between the results of Experi-ment 1 and subsequent experiments cannot bemade, there appeared to be only a negligibleeffect on total cups of coffee consumed andaverage intercup interval.

Sequences of ExperimentsThe right-hand column of Table 1 shows

the experiments in which each subject partic-ipated as well as the sequence of exposure toindividual experiments for each subject. Allsubjects participated in the characterization of

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Table 2Characterization of ad-libitum coffee drinking in 9 sub-jects during each subject's last 6 days in Experiment 1.Cups per day and cup durations in minutes are expressedas means, with SEM in parentheses; intercup intervals inminutes are expressed as medians with interquartile rangesin parentheses.

IntercupCup duration interval

Subject Cups per day (min) (min)

S-CI 17.00 (0.63) 18.95 (0.97) 41 (23-67)S-PO 14.67 (0.42) 11.85 (0.19) 61 (53-83)S-WA 18.33 (0.99) 3.86 (0.18) 50 (34-73)S-DA 15.17 (0.48) 30.73 (1.17) 61 (43-100)S-HA 17.83 (0.31) 18.70 (0.36) 45 (37-55)S-LE 17.00 (0.82) 14.75 (0.75) 52 (25-82)S-KA 13.17 (0.31) 12.85 (0.51) 60 (38-98)S-TO 13.33 (0.84) 22.27 (0.92) 55 (36-112)S-JO 10.50 (0.76) 11.44 (0.60) 93 (55-130)

ad-libitum coffee drinking (Experiment 1).Three subjects each participated in Experi-ments 2 to 5, which were conducted in se-quential order. Because at any given time only1 subject participated in research on coffeedrinking, subjects were arbitrarily assigned toexperiments in the order in which they par-ticipated in the research. Differences amongsubjects in the number of experiments com-pleted reflect differences in the length of timesubjects agreed to participate in the inpatientresearch.

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MIDNIGHT 6:0 A.M. NOON 606 P.M. MIDNIGHTFig. 1. Distributions of ad-libitum coffee drinking for

the 9 subjects in Experiment 1. Times at which individualcups of coffee were dispensed are represented by verticalhatch marks. For each subject, data are from a 24-hrperiod during the last 6 days of the experiment. The 24-hr period was selected for each subject such that the num-ber of cups consumed approximated the mean consumedduring the last 6 days.

EXPERIMENT 1:CHARACTERIZATION OF

AD-LIBITUM COFFEE DRINKINGThe objective of the initial experiment in

this series was simply to describe patterns of24-hr ad-libitum coffee intake in subjects withhistories of heavy coffee drinking.

METHODNine subjects with histories of heavy coffee

drinking participated (Table 1). Using thegeneral methods described previously, caffein-ated coffee was freely available 24 hr a day.Each cup of coffee was prepared from 2 g offreeze-dried caffeinated coffee. The experi-ment was continued at least 6 days and untilthere were no trends over the last 6 days innumber of cups per day. For purposes of dataanalysis, cup duration was defined as the timefrom dispensing a cup of coffee to the time thesubject returned the empty cup. Intercup in-terval was defined as the time between dis-pensing sequential cups of coffee.

RESULTSStable patterns of coffee drinking emerged

when subjects were given free access to coffeefor 6 to 10 days (mean: 7.5 days). Averagenumber of cups per day, cup duration, andintercup interval over the last 6 days are pre-sented in Table 2 for each of the 9 subjects.Although there were between-subject differ-ences, these measures were relatively stablewithin subjects as suggested by the measuresof variability. Representative within-day dis-tributions of coffee drinking for all 9 subjectsare presented in Figure 1. As shown in thefigure, during normal waking hours coffeedrinking tended to be rather regularly spaced,with a tendency for intercup intervals to be-come progressively longer throughout the day.Coffee drinking was erratic during mid-eve-ning and early-morning hours when subjectstypically slept. Over the 6-day period, 6 of the9 subjects drank some coffee between mid-night and 6:00 a.m. (range of the means was0.33 to 1.66 cups/night for the 6 subjects).

Figure 2 presents average intercup intervaland cup duration as a function of sequentialcups of the day. Intercup interval showed aprogressive increase from approximately 20 to80 min over successive cups. Cup duration, incontrast, showed a modest increase from the

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first to the second cup of the day and remainedrelatively stable over subsequent cups.

EXPERIMENT 2: MANIPULATION OFCOFFEE CONCENTRATION

Experiment 1 showed that orderly within-day and stable across-day patterns of coffeedrinking occur when subjects are given freeaccess to coffee. Experiment 2 was undertakento examine the sensitivity of coffee drinking tochanges in coffee concentration.

METHODThree subjects with histories of heavy cof-

fee drinking participated (Table 1). Using thegeneral methods described previously, freeze-dried caffeinated coffee was made availabledaily from 7:00 a.m. until 12:00 midnight.Subjects were told that the brand, strength,and caffeine content of the coffee might bechanged from day to day but the coffee wouldnever be changed within the day. Coffee con-centration was manipulated by varying theamount of caffeinated freeze-dried coffee fromwhich each 180-mL cup of coffee was made.Six concentrations corresponding to 0.5, 1, 2,4, 8, and 16 g of caffeinated coffee per cupwere examined; concentrations were exam-ined in a block randomized sequence acrossdays (a single concentration was examined ona given day and the order of concentrationswas random, with the constraint that all con-centrations occurred once before any concen-tration was repeated). Each block was re-peated four times. Although subjects were notexplicitly informed of the nature of the changein their coffee from day to day, gross differ-ences across the 32-fold concentration rangewere readily apparent to subjects by visual in-spection of a prepared cup of coffee. At 5:00p.m. each day, subjects rated the "strength"(7-point scale from "very weak" to "verystrong"), "bitterness" (7-point scale from "notat all bitter" to "very bitter"), and their "over-all liking" (5-point scale from "I dislike it" to"I like it very much") of the coffee they re-ceived that day.

RESULTSAs shown in Figure 3, there were orderly

concentration-related effects on all of the ma-jor dependent variables. As coffee concentra-tion was increased, cups consumed varied as

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an inverted U-shaped function, while intercupinterval was a U-shaped function. Average cupduration showed concentration-related in-creases at the highest concentrations. Totalcoffee consumed was an increasing function ofconcentration except for the highest concen-trations, at which it decreased somewhat.Subject ratings of coffee "strength" (notshown) and "bitterness" were monotonicallyincreasing functions of concentration, while"liking" was an inverted U-shaped function.

Representative within-day distributions ofcoffee drinking across the six concentrationsin all 3 subjects are presented in Figure 4. Assuggested by this figure, number of cups perday was an inverted U-shaped function ofconcentration and intercup interval was a U-shaped function of concentration (cf. Figure3). As in Experiment 1, analysis of sequentialintercup intervals generally showed increasesover successive cups of the day.

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EXPERIMENT 3: MANIPULATION OFCOFFEE CONCENTRATION AND

CAFFEINE DOSEExperiment 2 showed that coffee drinking

was an orderly function of coffee concentra-tion. The inverted U-shaped function relatingcups per day to coffee concentration suggestedthat intermediate coffee concentrations werereinforcing in that these concentrations reli-ably maintained coffee drinking at rates ex-ceeding the lowest (vehicle-like) concentra-tion. The experiment also demonstrated thefeasibility of conducting coffee-drinking ex-periments by manipulating the coffee contentson an across-day basis. In Experiment 2, themanipulation of coffee concentration and caf-feine concentration covaried (i.e., coffee andcaffeine concentration were purposely con-founded). Experiment 3 was undertaken tobegin to provide more information about therole of caffeine in coffee drinking by manip-ulating coffee concentration and caffeine doseindependently.


fee drinking participated (Table 1). Using thegeneral methods described previously, coffeewas made available daily from 7:00 a.m. until12:00 midnight. Subjects were told that thebrand, strength, and caffeine content of thecoffee might be changed from day to day butthe coffee would never be changed within theday. Coffee concentration was manipulatedover a four-fold range by varying the amountof decaffeinated freeze-dried coffee from whicheach cup was made; three concentrations cor-responding to 2, 4, and 8 g of decaffeinatedcoffee per cup were examined. Caffeine dosewas manipulated over two levels by usingeither decaffeinated coffee to which caffeinehad been added in the ratio of 100 mg caffeineanhydrous (USP) per 2 g freeze-dried coffee,or by using decaffeinated coffee to which pow-dered lactose had been added in a ratio similarto caffeine. The ratio of caffeine to powdered

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Fig. 4. Representative distributions of coffee drinkingfor each of the 3 subjects in Experiment 2. Times at whichindividual cups of coffee were dispensed are representedby vertical hatch marks. Coffee concentration was variedacross days; data are from 1 of the 4 days at each concen-tration. Selection of data for presentation was quasi-ran-dom.

decaffeinated coffee was chosen such that atthe manufacturer's recommended coffee con-centration (2 g per cup) each cup would con-tain 100 mg caffeine. Although this caffeineamount is higher than the equivalent brandof caffeinated freeze-dried coffee-52 mg/cup("Instant Coffees," 1979), it is in the mid-range of caffeine doses that normally occur incups of brewed coffee (Bunker & Mc-Williams, 1979; Gilbert et al., 1976). Lactosewas used in the decaffeinated conditions inamounts similar to caffeine in the caffeinatedconditions in order to match the appearanceof the unprepared coffee in the two conditions.A previous study by Goldstein (1964) andpreliminary trials at the 2-g concentration(Griffiths, unpublished observations) sug-

Fig. 3. Effects of coffee concentration on coffee drinking and subjective ratings shown separately for the 3 subjectsin Experiment 2. y axes: number of cups per day, intercup interval in minutes, cup duration in minutes, total coffeeper day in grams, coffee bitterness, and coffee liking; x axes: coffee concentration in grams per cup, log scale. Eachdata point and bracket indicates mean ± 1 SEM for 4 days (N = 4). Absence of bracket indicates radius of data pointis greater than 1 SEM; the upper bracket for Subject S-CI's intercup interval at the 0.5-g concentration has beendeleted for clarity.

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Fig. 5. Effects of coffee concentration and caffeine dose on coffee drinking and subjective ratings, for each of the3 subjects in Experiment 3. y axes: number of cups per day and coffee bitterness; x axes: coffee concentration in gramsper cup, log scale. Filled and unfilled data points indicate caffeinated and decaffeinated conditions, respectively. Eachdata point and bracket indicates mean ± 1 SEM for 4 days (N = 4). Absence of a bracket indicates that the radius ofthe data point is greater than 1 SEM.

gested that the decaffeinated coffee plus lac-tose and the decaffeinated coffee plus caffeine(100 or 150 mg per cup) could not be reliablydifferentiated on the basis of taste or appear-ance. The six experimental conditions (2, 4,and 8 g of decaffeinated coffee and 2, 4, and8 g of caffeinated coffee) were examined in ablock randomized sequence across days andeach block was repeated four times. As in Ex-periment 2, at 5:00 p.m. subjects rated"strength," "bitterness," and their "liking" ofthe coffee available that day.

RESULTSIn general, variation of coffee concentration

produced orderly effects consistent with thosein Experiment 2; surprisingly, there were no

consistent differences between the caffeinatedversus decaffeinated conditions on the behav-ioral and subjective measures.As shown in Figure 5, cups of caffeinated

coffee consumed decreased monotonically withconcentration, an effect similar to that ob-served at similar concentrations in Experi-

ment 3 (cf. Figure 3). Cups of decaffeinatedcoffee consumed also decreased with concen-tration. There were no consistent differencesacross the 3 subjects between caffeinated ver-

sus decaffeinated conditions in number of cupsconsumed. Subject ratings of "bitterness"(Figure 5), "strength," and "liking" weresimilar to the results in Experiment 2 at thesesame coffee concentrations. Again, there were

no consistent differences between the caffein-ated versus decaffeinated conditions on theseratings (e.g., bitterness in Figure 5).

EXPERIMENT 4:MANIPULATION OFCAFFEINE DOSE

Experiment 3 began to explore the role ofcaffeine in coffee drinking by comparing theself-administration of caffeinated versus de-caffeinated coffee at three different coffee con-centrations. No consistent differences betweenthe caffeinated and decaffeinated conditionswere found. Experiment 4 was undertaken toexplore further the role of caffeine in coffee

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fee drinking participated (Table 1). With theexception of some changes in coffee availabil-ity and testing at the beginning of the day, thegeneral methods were similar to those used inExperiments 2 and 3. As before, subjects weretold that the brand, strength, and caffeine con-tent of the coffee might be changed from dayto day but the coffee would never be changedwithin the day. Unlike previous experiments,subjects were required to start their first cupof coffee for the day at 7:30 a.m. and theywere permitted no additional coffee until 8:45a.m. At 8:30 a.m. arm tremor was assessed asdescribed below. From 8:45 a.m. until 12:00midnight subjects were given free access to cof-fee as in Experiments 2 and 3. The primaryrationale of the 7:30 a.m. "sample" cup andthe delayed availability of subsequent coffeewas to attempt to reduce the likelihood of in-advertent caffeine overdose; inasmuch as caf-feine content was to be varied over a widerange from day to day, it was reasoned thatthe sample cup and delay interval would al-low subjects the opportunity to experience fullythe effects of the coffee before the beginningof the period of free availability.

Caffeine dose was manipulated by varyingthe amount of caffeine added to a standardconcentration of decaffeinated coffee. All cupsof coffee were made from 2 g freeze-dried de-caffeinated coffee (the manufacturer's recom-mended concentration) to which caffeine an-hydrous (USP) and/or powdered lactose hadbeen added. In order to match the appearanceof the unprepared coffee across conditions, theamount of caffeine, lactose, or caffeine/lactosecombination was held constant across condi-tions. Five or six dose conditions involving 0,25, 50, 100, 200, and 400 mg caffeine anhy-drous per cup were examined; conditions werestudied in a block randomized sequence acrossdays and each block was repeated five times.Subject-DA was studied at all six caffeinedoses. Because at the beginning of the exper-iment S-HA and S-LE sometimes reportedsymptoms suggesting caffeine toxicity (e.g.,having an upset stomach, feeling jittery), the400-mg condition was not studied in S-HAand was examined on only 1 day in S-LE. As

in Experiments 2 and 3, at 5:00 p.m. subjectsrated "strength," "bitterness," and their "lik-ing" of the coffee available that day.

Arm TremorAt 8:30 a.m., 1 hr after receiving the "sam-

ple" cup of coffee, subjects participated in anarm-tremor task on which dose-related sen-sitivity to caffeine has previously been re-ported (Chait & Griffiths, 1983). A pretreat-ment interval of 60 min between dosing andtesting is appropriate because caffeine is rap-idly absorbed and distributed (Gilbert, 1976)and has been shown to produce reliable effectson verbal self-reports with this pretreatmentinterval (Chait & Griffiths, 1983). For thistask, the subject held a metal stylus (2 mm indiameter, approximately 30 cm long) in thepreferred hand. With the arm fully extended,the subject inserted the stylus into a 6-mmdiameter hole in a metal plate. The metal platewas mounted vertically, facing the subject, ona rack at about shoulder level. The subjectwas instructed to hold the stylus as steadily aspossible without touching the sides of the hole.After the subject inserted the stylus into thehole, a timer was started and the number ofcontacts in a 20-s period was automaticallyrecorded.

RESULTSFigure 6 presents the major results of ma-

nipulating caffeine dose. For all 3 subjects,cups consumed increased slightly from 0 to 25or 50 mg caffeine, thus providing some limitedevidence for the reinforcing effects of caffeinein coffee (maximum effect for decaffeinatedvs. caffeinated conditions, respectively: 11.8 +0.8 vs. 15.8 ± 1.6 cups in S-DA; 15.2 ± 0.3vs. 16.6 ± 0.2 cups in S-HA; and 9.6 ± 1.1vs. 13.4 ± 1.3 cups in S-LE). For all 3 sub-jects, higher caffeine doses (50 to 400 mg)produced an orderly dose-related suppressionin cups consumed. Total caffeine consumed(including 2 mg caffeine per 2 g of decaffein-ated coffee) increased monotonically with doseexcept at the highest dose tested in 2 subjects(S-DA and S-HA) at which it decreasedslightly. The intercup-interval function of doseand the cup-duration function of dose did notvary consistently across subjects (not shown).Subject ratings of "bitterness" showed cleardose-related increases in S-DA, but only rel-atively small elevations at the highest dose

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CAFFEINE DOSE (mg per cup)Fig. 6. Effects of caffeine dose on coffee drinking, subjective ratings, and arm tremor, for each of the 3 subjects

in Experiment 4. y axes: number of cups per day, total caffeine per day in grams, coffee bitterness, coffee liking, andnumber of stylus contacts from the 8:30 a.m. tremor measure; x axes: caffeine dose in milligrams of caffeine added toeach cup of decaffeinated coffee. Each data point and bracket indicates mean ± 1 SEM for 5 days (N = 5) except forS-LE at 400 mg, at which N = 1. Absence of a bracket indicates that the radius of the data point is greater than 1SEM. Due to an equipment malfunction, tremor data were not collected for Subject S-LE at 400 mg.

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tested in S-HA and S-LE. Ratings of coffee"strength" (not shown) were not sensitive tocaffeine-dose manipulations. Subject ratingsof "liking" were generally similar to cups con-sumed, showing dose-related decreases as dosewas increased from intermediate to high levels(50 to 400 mg). Finally, the 8:30 a.m. mea-sure of arm tremor (1 hr after the sample cup)showed dose-related increases in all 3 subjects.

Representative within-day distributions ofcoffee drinking across the doses examined arepresented in Figure 7. As suggested by thisfigure, average number of cups was an in-verted U-shaped function of caffeine dose (cf.Figure 6). Figure 7 also shows that at thehighest caffeine doses (200 and 400 mg), sub-jects sometimes abruptly stopped drinking cof-fee relatively early during the coffee-drinkingday. This effect occurred occasionally in eachof the 3 subjects. As a consequence, the inter-cup interval function of dose tended to be er-ratic both within and across subjects. As inprevious experiments, analysis of sequentialintercup intervals showed increases over suc-cessive cups of the day.

EXPERIMENT 5: EFFECTS OFCAFFEINE PRELOAD

In Experiment 4 the role of caffeine in cof-fee drinking was investigated by manipulatingthe caffeine dose in the coffee. The study dem-onstrated that high doses of caffeine (i.e., 200or 400 mg/cup) suppressed coffee drinking.The study also provided some limited evidencefor reinforcing properties of low doses of caf-feine: Compared with the decaffeinated con-dition, low doses of caffeine (25 or 50 mg percup) were correlated with a slightly highernumber of cups consumed. Experiment 5 wasundertaken to provide additional informationon caffeine and coffee drinking, by exploringthe effects on coffee drinking of preloadingsubjects with caffeine in capsules.


fee drinking participated (Table 1). The gen-eral methods were similar to those used pre-viously and the daily procedure was similarto that in Experiment 4 except that subjectsingested capsules at 7:30 a.m. in place of in-gesting a sample cup of coffee. Each day at7:30 a.m. subjects ingested two opaque size 0

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Fig. 7. Representative distributions of the 3 subjects'coffee drinking in Experiment 4. Times at which individ-ual cups of coffee were dispensed are represented by ver-tical hatch marks. Caffeine doses indicate milligrams ofcaffeine added to each cup of decaffeinated coffee. Dosewas varied across days; data are from 1 of the 5 days ateach dose, except that S-LE was exposed to 400 mg foronly 1 day. Selection of the data for presentation wasquasi-random.

gelatin capsules with approximately 210 ccwater. Subjects were informed that the cap-sules contained a placebo or one in a widerange of doses of caffeine. The capsules, whichwere administered under double-blind condi-tions (i.e., neither the subjects nor staff knewthe contents), contained caffeine anhydrousand/or lactose. Five doses were examined, in-volving 0, 100, 200, 400, and 800 mg caffeineanhydrous; the conditions were studied in ablock randomized sequence across days andeach block was repeated five times.

At 8:30 a.m. arm tremor was assessed asdescribed in Experiment 4 and subjects ratedmagnitude of the "stimulant effect" from thecapsules on a 7-point scale from "no effect"to "very strong effect." As in Experiment 4,from 8:45 a.m. until 12:00 midnight subjectswere given free access to coffee. As before,subjects were told that the brand, strength,and caffeine content of the coffee might bechanged from day to day but the coffee would

143


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144


never be changed within the day. In fact, cof-fee was not manipulated in this experiment;all cups of coffee were made from 2 g freeze-dried decaffeinated coffee (the manufacturer'srecommended concentration) to which 100 mgcaffeine anhydrous was added. This amountof caffeine is in the mid-range of caffeine dosesthat normally occur in cups of brewed coffee(Bunker & McWilliams, 1979; Gilbert et al.,1976) and the ratio of decaffeinated coffee tocaffeine was identical to that used in Ex-periment 3. As in Experiments 2, 3, and 4, at5:00 p.m. subjects rated "strength," "bitter-ness," and their "liking" of the coffee avail-able that day.

RESULTSFigure 8 presents the major results of ma-

nipulating the caffeine preload dose. In all 3subjects, as preload dose increased, cups con-sumed decreased, and intercup interval in-creased. Although the magnitude of thesechanges was modest (e.g., difference between0- and 800-mg preload ranged between 1.6and 3.0 cups per day across subjects), the pre-load effect was clearly dose-related. Despitethe decreases in cups consumed, total caffeineconsumed per day (preload dose plus 102 mgper cup of coffee) increased with increases inpreload dose. Cup duration as a function ofpreload dose did not vary consistently acrosssubjects (not shown). Subject ratings of coffee"strength" (not shown), "bitterness," and"liking" were insensitive to preload dose. Fi-nally, with regard to the 8:30 a.m. measuresof tremor and stimulant effect, each of the 3subjects showed clear dose-related sensitivityto at least one of these two measures of themagnitude of the preload drug effect.

Inspection and analysis of within-day dis-tributions of coffee drinking revealed no strik-ing effects of preload dose. Intercup intervalsincreased over successive cups of the day un-der all preload doses in all 3 subjects (e.g.,mean ± SEM for first and last intercup inter-val, respectively, under the 0 preload condi-tion were 22.2 ± 4.9 and 122.6 ± 11.1 for

S-LE; 19.2 ± 4.1 and 86.2 ± 11.5 for S-KA;and 13.8 ± 2.3 and 89.8 ± 20.4 for S-TO).Although average intercup interval increasedwith increases in preload dose (cf. Figure 8),the latency to start the first cup of the day andthe length of the initial intercup intervals ofthe day did not show dose-related increaseswith preload dose as would be expected if in-tercup interval were predominately controlledby prior caffeine intake.

DISCUSSIONThe present set of studies has shown coffee

drinking in heavy coffee-drinking subjects tobe stable and orderly behavior. When cups ofcoffee were freely available, coffee drinkingtended to be rather regularly spaced duringthe day with intercup intervals becoming pro-gressively longer throughout the day. That caf-feinated coffee was reinforcing at intermediate(i.e., usual) concentrations was suggested bythe finding that intermediate concentrationsreliably maintained higher numbers of cupsper day than the lowest (vehicle-like) concen-tration (Figure 3).The progressive increase in intercup inter-

val over the initial cups of the day cannot beattributed solely to accumulating caffeine levels(e.g., a caffeine-satiation mechanism) becausethe effect occurred at a range of caffeine con-centrations (Experiment 4) and because caf-feine preloads did not influence initial inter-cup intervals of the day (Experiment 5).

Although coffee drinking was suppressedboth by high caffeine doses per cup (Figure6) and by high coffee concentrations (Figure3), the bases for the caffeine-related versusconcentration-related suppression may be dif-ferent. Manipulation of coffee concentrationproduced orderly effects on intercup intervaland cup duration (Figure 3) while caffeinedose manipulations had only erratic effects onthese measures. Further, in contrast to themanipulations of coffee concentration, highcaffeine doses sometimes produced abrupt ces-sations of coffee drinking (Figures 4 and 7).

Fig. 8. Effects of caffeine preload in capsules on 3 subjects' coffee drinking, subjective ratings, and arm tremor inExperiment 5. y axes: number of cups per day, intercup interval in minutes, total caffeine per day in grams, coffeebitterness, coffee liking, number of stylus contacts during the 8:30 a.m. tremor measure, and 8:30 a.m. stimulant ratingof capsules; x axes: preload dose of caffeine in milligrams. Each data point and bracket indicates mean ± 1 SEM for5 days (N = 5). Absence of a bracket indicates that the radius of a given data point is greater than 1 SEM.

145


The present studies provide some evidencethat caffeine can suppress coffee drinking. InExperiment 4, high caffeine doses (200 and400 mg per cup) consistently reduced thenumber of cups consumed below that observedin the decaffeinated, low, and intermediatecaffeine-dose conditions. In Experiment 5,caffeine preloads consistently but modestlyreduced the number of cups consumed in adose-dependent fashion. These results extendthose of Kozlowski (1976), who manipulatedthe caffeine content of coffee (25, 50, or 100mg per cup) and found that fewer cups wereconsumed at the highest dose than at the lowerdoses.The present studies provide very limited

evidence for the reinforcing properties of caf-feine. In Experiment 4, low caffeine doses (25or 50 mg per cup) were correlated with aslightly higher number of cups consumed thanin the decaffeinated condition. Although themagnitude of the effect was small, it occurredin all 3 subjects. It is unlikely that the effectis due to taste differences because ratings of"bitterness" and "strength" did not differen-tiate the caffeinated (25 and 50 mg per cup)from the decaffeinated doses and because pre-vious taste comparisons (Goldstein, 1964;Griffiths, unpublished observations) suggestedthat caffeinated (100 or 150 mg per cup) anddecaffeinated coffee cannot be differentiatedreliably. Thus, these results suggest that lowdoses of caffeine in coffee may be reinforcing(i.e., may maintain self-administration abovecontrol levels).The possible reinforcing properties of caf-

feine notwithstanding, it is noteworthy that,at usual concentrations, drinking of decaffein-ated coffee was well maintained in the presentstudies. In fact, the numbers of cups consumedper day of normal-strength decaffeinated cof-fee did not differ greatly from the correspond-ing numbers for normal-strength caffeinatedcoffee (cf. conditions of 2 g per cup in Exper-iment 3; conditions of 0 and 100 mg per cupin Experiment 4). Although it is possible thatdecaffeinated-coffee drinking was maintainedby caffeine-related conditioned reinforcers(e.g., taste and sensory stimuli), there are nu-merous substances in decaffeinated coffee thatmight have behavioral (including reinforcing)effects (Boublik, Quinn, Clements, Hering-ton, Wynne, & Funder, 1983; Cohen & Booth,

1975; M. A. Spiller, 1984). Future studiesshould further investigate the maintenance ofdecaffeinated-coffee drinking by determiningthe extent to which intake is maintained overprolonged periods of continuous availability.

Although the number of cups consumed wasresponsive to manipulations of coffee concen-tration (Experiment 2), of caffeine dose (Ex-periment 4), and of caffeine preloads (Exper-iment 5), the present experiments did notprovide evidence for precise regulation (i.e.,titration) of coffee or caffeine intake. Throughthe intermediate portions of the concentrationand caffeine dose-effect curves, there weresubstantial increases in total consumption ofcoffee (Figure 3) and caffeine (Figure 6).Further, caffeine preloads produced substan-tial increases in total caffeine consumed (Fig-ure 7). This lack of precise regulation of cof-fee and caffeine intake is consistent with avariety of studies of drug self-administrationin both humans and nonhumans, which haveshown that dose manipulations are typicallynot accompanied by precise regulation of drugintake (cf. Griffiths, Bigelow, & Henning-field, 1980).

Although it is sometimes assumed that drug-produced euphoria and liking are determi-nants of drug self-administration, such as-sumptions can reasonably be questioned, anddissociations between such subjective mea-sures and behavioral measures of drug rein-forcement have been reported (Griffiths, Big-elow, Liebson, & Kaliszak, 1980; Schuster,Fischman, & Johanson, 1981). The results ofthe present studies provide an opportunity toexamine the relationship between subject rat-ings of their liking of the coffee and corre-sponding rates of coffee self-administration.Examination of data from Experiments 2 and4, which involved manipulation of coffee con-centration and caffeine dose (Figures 3 and6), indicates a generally close covariation be-tween cups consumed and reported liking.However, the results of Experiment 5, whichinvolved administration of caffeine preloaddoses, showed that caffeine preload decreasedcups consumed without influencing subjects'reports of liking the coffee (Figure 8). Al-though there are undoubtedly several plausi-ble explanations for this dissociation betweencups consumed and reports of liking, the dis-sociation further emphasizes the fact that be-

146

HUMAN COFFEE DRINKING 147

havioral measures of drug self-administrationneed not always covary with verbal reportspresumed to reflect reinforcing properties.

Because caffeine is a bitter alkaloid, subjectratings of coffee "bitterness" were used in thepresent study in an attempt to assess the ex-tent to which subjects discriminated betweendifferent caffeine conditions on the basis oftaste. High concentrations of caffeine pro-duced elevations in bitterness ratings com-pared to decaffeinated conditions in all 3 sub-jects tested (Experiment 4, Figure 6).However, at a more "usual" caffeine concen-tration in coffee (i.e., 100 mg per cup), 5 of 6subjects tested did not differentiate betweencaffeinated and decaffeinated conditions (2 gper cup conditions in Experiment 3 [Figure5]; 0 and 100 mg per cup conditions in Ex-periment 4 [Figure 6]). This finding is con-sistent with the results of previous taste com-parisons that suggested that decaffeinatedcoffee plus lactose (placebo) cannot be reliablydifferentiated from decaffeinated coffee plus100 or 150 mg caffeine (Goldstein, 1964; Grif-fiths, unpublished observations). However, thesixth subject (S-DA, Figure 6) rated coffeecontaining 100 mg of caffeine as being slightlymore bitter (3.6 ± 0.9) than the decaffeinatedcoffee (2.2 ± 0.4). The finding of differencesamong subjects with respect to their ability todetect caffeine at normal concentrations isconsistent with the prediction of Hall, Bar-toshuk, Cain, and Stevens (1975), who dem-onstrated population differences in taste sen-sitivity to caffeine. In conducting studiescomparing "usual" concentrations of caffein-ated versus decaffeinated coffee, investigatorsshould not assume that all subjects will beunable to differentiate between conditions onthe basis of taste.The present set of studies has revealed cof-

fee drinking to be a stable and orderly formof drug self-administration behavior that isreadily amenable to experimental analysis us-ing intensive within-subject experimental de-signs. One focus of this research was to beginto explore the role of caffeine in coffee drink-ing. Under the limited set of conditions ex-amined, these studies provide some evidencefor both the suppressive and the reinforcingeffects of caffeine on coffee consumption.Valuable additional information about caf-feine's role in coffee drinking will be provided

by future studies in which caffeine is manip-ulated on a more chronic basis for periods ofweeks, rather than on the acute, daily basis aswas done in the present studies.

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Behavioral treatment of excessive coffee and tea drink-ing: A case study and partial replication. BehaviorTherapy, 12, 543-548.

Bigelow, G., Griffiths, R., & Liebson, I. (1975). Ex-perimental models for the modification of human drugself-administration: Methodological developments inthe study of ethanol self-administration by alcoholics.Federation Proceedings, 34, 1785-1792.

Boublik, J. H., Quinn, M. J., Clements, J. A., Hering-ton, A. C., Wynne, K. N., & Funder, J. W. (1983).Coffee contains potent opiate receptor binding activity.Nature, 301, 246-248.

Bunker, M. L., & McWilliams, M. (1979). Caffeinecontent of common beverages. Journal of the AmericanDietetic Association, 74, 28-32.

Chait, L. D., & Griffiths, R. R. (1983). Effects of caf-feine on cigarette smoking and subjective response.Clinical Pharmacology and Therapeutics, 34, 612-622.

Cohen, S., & Booth, G. H., Jr. (1975). Gastric acidsecretion and lower-esophageal-sphincter pressure inresponse to coffee and caffeine. New England Journalof Medicine, 293, 897-899.

Dews, P. B. (1982). Caffeine. Annual Review of Nutri-tion, 2, 323-341.

Ernster, V. L. (1984). Epidemiologic studies of caffeineand human health. In G. A. Spiller (Ed.), The meth-ylxanthine beverages andfoods: Chemistry, consumption,and health effects (pp. 377-400). New York: Liss.

Foxx, R. M., & Rubinoff, A. (1979). Behavioral treat-ment of caffeinism: Reducing excessive coffee drink-ing. Joumnal of Applied Behavior Analysis, 12, 335-344.

Gilbert, R. M. (1976). Caffeine as a drug of abuse. InR. J. Gibbons, Y. Israel, H. Kalant, R. E. Popham,W. Schmidt, & R. G. Smart (Eds.), Research advancesin alcohol and drug problems (Vol. 3, pp. 49-176). NewYork: Plenum Press.

Gilbert, R. M. (1984). Caffeine consumption. In G. A.Spiller (Ed.), The methylxanthine beverages and foods:Chemistry, consumption, and health effects (pp. 185-213).New York: Liss.

Gilbert, R. M., Marshman, J. A., Schwieder, M., & Berg,R. (1976). Caffeine content of beverages as con-sumed. Canadian Medical Association Journal, 114, 205-208.

Goldstein, A. (1964). Wakefulness caused by caffeine.Naunyn-Schmiedebergs Archiv ffir Experimentelle Path-ologie und Pharmakologie, 248, 269-278.

Graham, D. M. (1978). Caffeine-Its identity, dietarysources, intake and biological effects. Nutrition Re-views, 36, 97-102.

Greden, J. F. (1981). Caffeinism and caffeine with-drawal. In J. H. Lowinson & P. Ruiz (Eds.), Sub-stance abuse: Problems and perspectives (pp. 274-286).Baltimore: Williams & Wilkins.

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Griffiths, R. R., Bigelow, G. E., & Henningfield, J. E.(1980). Similarities in animal and human drug-tak-ing behavior. In N. K. Mello (Ed.), Advances in sub-stance abuse (Vol. 1, pp. 1-90). Greenwich, CT: JAIPress.

Griffiths, R. R., Bigelow, G. E., & Liebson, I. (1976).Human sedative self-administration: Effects of inter-ingestion interval and dose. Journal of Pharmacologyand Experimental Therapeutics, 197, 488-494.

Griffiths, R. R., Bigelow, G. E., Liebson, I., & Kaliszak,J. E. (1980). Drug preference in humans: Double-blind choice comparison of pentobarbital, diazepamand placebo. Journal ofPharmacology and ExperimentalTherapeutics, 215, 649-661.

Griffiths, R. R., Henningfield, J. E., & Bigelow, G. E.(1982). Human cigarette smoking: Manipulation ofnumber of puffs per bout, interbout interval and nico-tine dose. Journal of Pharmacology and ExperimentalTherapeutics, 220, 256-265.

Hall, M. J., Bartoshuk, L. M., Cain, W. S., & Stevens,J. C. (1975). PTC taste blindness and the taste ofcaffeine. Nature, 253, 442-443.

Instant coffees. (1979). Consumer Reports, 44, 569-572.James, J. E., Stirling, K. P., & Hampton, B. A. M.

(1985). Caffeine fading: Behavioral treatment of caf-feine abuse. Behavior Therapy, 16, 15-27.

Kozlowski, L. T. (1976). Effect of caffeine on coffeedrinking. Nature, 264, 354-355.

Schuster, C. R., Fischman, M. W., & Johanson, C. E.(1981). Internal stimulus control and subjective ef-fects of drugs. In T. Thompson & C. E. Johanson,(Eds.), Behavioral pharmacology of human drug depen-dence (pp. 116-129). National Institute on Drug AbuseResearch Monograph No. 37 (DHHS Publication No.ADM 81-1137). Washington, DC: U.S. GovernmentPrinting Officc.

Spiller, G. A. (Ed.) (1984). The methylxanthine bever-ages and foods: Chemistry, consumption, and health ef-fects. New York: Liss.

Spiller, M. A. (1984). The chemical components of cof-fee. In G. A. Spiller (Ed.), The methylxanthine bever-ages andfoods: Chemistry, consumption, and health effects(pp. 91-147). New York: Liss.

Weiss, B., & Laties, V. G. (1962). Enhancement ofhuman performance by caffeine and the amphet-amines. Pharmacological Reviews, 14, 1-36.

Received May 1, 1985Final acceptance December 7, 1985

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