Tobacco Documents Online

I I I I I I I I I I I I I I I I I I I 1026 OiiUG DEKMD£P+CE / C.,WTER 22 22.4 CAFFEINE AND TOBACCO DEPENDENCE JOIl.V F GREDE.V. .if D. INTRODUCTION Disorders resulting from caffcinc and tobacco use were in- cludcd for the first time in the Amcrican Psychiatric Associ- ation's third edition of the Diu,i~nnstir and Sralislirul.llunual of,tlenrul Dnrtrrlrrs (DSM-111). Sctcral conditions %4crc rcc- ognized: (1) caffeine intoxication (305.90). categonzcd under Organic Mental Disorders: (2) tobacco withdrawal (292.00), also listed under Org3nic Mcntal Disorders: and (3) tohacco dcpcndcncc (305.14), classificd >;ithin the group of Substancc Usc Disorders. Although caffcinc and tobacco arc popularl} considered nondrugs. compelling pharmacological c%idcncc and a bur- gconing literature document their clinical impomncr and justif~ their inclusion in am complete nosological s\stem of mcntal disordcrs. CAFFEINE DEFINITION AND HISTORY Cafcinism is a pharmacolog;cal statr of acutr or chruntc toaicit} that rcsults from the ingestion of high doscs of caffrinc. w hcthcr in the form of cofl'cc. tea. cola dnnks. cocoa. chocolatc. or read l% a%ailahlc mcd cations. including o\cr- thc-tountcrand prescnpti~panalgnics, cold preparations. stimulants. and appctitc supressants`CafTrrmsm is a multifaceted s\•ndromc Tencralh cttaractcrizcd b~ a constellation of anxictt and affcctivc i.mptomso slecp disruptions.qs .c ological or somatic com- ~laints. and -nhdraµal manifesUtions n addition to inducing its oµn charactensuc clinical s~ndromc in othcrMtsc hcalth% ind ~iduals. the drug ma} accentuate other ps~chopathologtcs and has tmpOrtant widcst+rcad intcnnions with commonl% uscd psychutnc treatments. Caffeine originatcs natunll% in 63 spccics of plants, including tea ka\es. coffee seeds (bcans). kola nuts, cocoa trccs. ilcx plants or matc, and cassina. A+ailahlc in various commercial forms for more than a thousand \ears. its histor\ is chcckcrcd with med cal, moral, and Icgal dctaotcs ahout potential bcncfiu and dangcrs. An I8ih{cntur\ caf- fcinc opponent Lamented that the habitual coffee dnnkcr was a suffercr who is tremulous and loses his self-command. he is subjcct to fits of agitation and dcpression: he loscs color and has a haggard appcarancc. The appetite falls ofT, and st mptoms of gsstnc atarrh ma\ be manifcstcd. The hcan also suf(crs: it palp utn or it intcrmtts. As with other such agcnts, a rcncr.cd dosc of the poison gj~cs tcmporar) rclicf, but at the cost of further m scr.. Prohibitionists oftcn rcqucsted that coffee and tw hc banncd. but such effons gencrall\ failed. The followtng dcscnptton of a 16th- antur~ pattcrn in Europe chrontcies such fatlurc: ... the (cofTccJ habit had become so stronR and the use of it so acncrall} agrocablc. that the people conttnucd, notNtthstand nF ail proh b tions. to dnnk it in their oKn housc-s Thc ofT'ccrn o( the policr, seeing thc} could not supprcss the use of it allowed of thc selling it. on pa\ing a ux: and the dnnktng it pro%tdcd it was not done opcnl}: so that it was drunk in pan cular placcs. M-ith thc doors shut. or in thc back room of some of the shopl.ccpcrs houus

I I I I I I I I 1 I I I I I I i I I I This dcscnption pro% ldes an lntnguing parallel to current debates atk ut rannahls, hallucinogens. opiatcs, cocalnc. and other psycho- troplc suhstances. McJiral conccrn regarding caffeinc<ontaining substances is leg- cnLJan. In a wmeKhat hemusing ponrn~al from 1774, c~cn ensiron- mcnt.il and puhlic health tssues were introduced by a Mntcr to the London Public A6cnlscr who worncd that `four or fivc hundrrd chcsu of tea ha~e so contaminated the water in Boston harbour, that the fish ma~ hasc contacted a disorder not unlike the ncnous complaints of the hod).' As carly as 1811, an antinenous tca was ofTcrcd for sale In I909. Bntlsh doctors µcrr concerned that tea produced a strangc and citreme degrec of depn-uion. l'nfonunatcly. thnwghout its flamho~ant histon both proponents and opponents tendcd to ciaggcratc the cfTccts o(cafielnc use, a pattern encouraged b~ tnadeyuatc medicaJ documentation. EPIDEMIOLOGY Table 22.4-1 lists the common sourccs of cafTcinc in today's society, with approximate dosages for each, as well as some recently introduced caffeine-frer products. Although numerous surtieys hasc assessed patterns of coffce or tea use, the exact incidence and pre~alence of caffeinism are unknuµn. More than 60 percent of all Americans over 10 years of age ha%e some caffeine usc: oser 80 percent of the adults report coffee use, and more than 50 percent of adults hatie consumed tca~,About 20 to 30 percent of all adult Americans consume more than 500 mg of caffeine a day. Because doses exceeding 250 mg a day are considered phar- macologically largc, an intake of this magnitude significantly -predisposes to caffcinisrn. Thus. a substantial percentage of the U.S. population is at high nsk for periodic de>,elopment ofsymptoms, and an estimated 10 percent (point pre%alence) of tionh Americans probably hase caiTcinism Among hos- prtalved ps~chiatnc patients, more than'0 percent reported cafTcine consumption exceeding 750 mg a day from all sources. Most caffeine consumers do not develop caffeinism. whcn they do. the s~ndrome charactcnstically appears only after ~cars of consumption. the a%crage patient being hctueen 30 and 50 ±ran of age. No genetic patterns for caffeinism ha%c been firmly identified, and there is little agreement about any prcdlspusing pretourhid personalit} profiles. Because of the gruwing clinical and media emphasis on caffeine's occa- sional deleterious efTects. many medicinal and soft drink firms rcccntl~ ha%e remo~ed cafT'rine from their commodities (re- (lctitcd in Table 22.4- I), and there is a trend toward increasing consumption of dccatTeinated coffee and tea. CAUSES Peer pressure, media ad%crtising. cultural and eth- nic inf)uences, and modeling undoubtedly predispose to the initiation of catTcine intake. Once started, consumption is rctnfitrced b5 accomparring pleasant social interactions, as- slxtwuon wtth such actisitics as eating and smoking. and conditioned responses stemming from ca(Teine's ef7ecu on tastc, smell, and temperaturr (oral and olfacton gratification). Catleine's pharmacological actions. hov.etier, seem to be most imponant in e~.plsining the drug's populant~. The pharTna- colkj~ of the drug is currently of great-itQterest because new tindings indicate that it in(luenccs benzodiazcpine and. per- haps. opiate receptor sites. Established pharmacological ac- tt~rns must be underStood if cafYeinism is to be objectisely appraised. Pharmacology Caffeine is a trimeth~lated xanthine (1.3,7- tnmcth~Nanthine) that differs from theoph~llinc and theo- bromine onl~ in the number of ineth%Iated sites. Meth}lation on rxntuon I accounts for central nervous system (CNS) sttmul,ttion, that on position 3 is predominantly responsible for dluresis, and that on position 7 induces cardiac stimula- tion Because of its structure, caffeine impacts each of these ph~siol,Tjeal s%stems. as illustrated in the left-hand column Of Table 22.4-2. After ingcstion, the drug is absorbed in tissues µithin minutes, with peak plasma level developing 30 SoCloa1221 / CAFFEINE AND ToeACCO DEP£NDENCE TlkBIE 22 S--I Some Common Sources of Catf6ne and Representattve DecatieinateC Products Source Bc%cragcs Fresh dnp coffee Breµcd cof(ct Dccaffclnatcd cofTec lnstanl coffee Tea t Ica(1 Tea t bagged) Cocoa Sclected soft drinks Traditional cola dnnk i Pepsi. Coke. Tab, Ro%al CroMn, Pcpst Llght. Dr Pepper) Mountain DcK Canada Dn Ginger Ale Coke CatTclne Free Like Pepsi Free 7 l' p Spntc Syuln Tab Caffeine Free Ptrxnption medications APCs (asplnn. phcnacetln. caffeine) Cafergot Danon compound flonnal ttlgral ON cr-thc{ountcr analgesics with caffcinc Aspinn compound BC Tablet Bromo-Scltler Caprun Comeback Copc DUlor Easy•.1lens E ti.•L si n n Gax1.~'s Headache PuMder Mcd.ii he !stura noz %tldol Nilain P4C Prc-.%tcns Stanh,x•k Tablets Stanhack PoMder Tngesle Vanquish O%er-the-euunter analgesics Mithout catTeine Anacin Aspinn Empmn Pamplnn Man< oser-the-countcr cold preparations Oser-the-counter stimulants and appetite supprrssants Amosut Tablets Anorcxtn Capsules Appedrine Tablets CalTcdnnc Capsulcs Dr-,atnm Capsules Doublc-E Alertness \odoz Tablets Odnnc,t Tablets Prolamine Capsules Qulrk-Pcp Tablets Spantrol Capsules Tlrend Tablets Verb TD Capsules Vtsann Tablets Wakoz Chocolate bar or ounce of baking chocolate ' Cup = 5-6 ounce•s: soft dnnks - 8-12 ounces. 1027 Aprr„ um.uf AMWNS ~!f Ca(Terne per Cnu' Cup 100-140 mg 90-110 mg 2-4 mg 66-11b mg 30-' S mg 42-100 mg 5-50 mg 41u_ss :5-50 mg 25-50 mg 0 mg 0 mg 0 mg 0 mg 0 mg 0 mg 0 mg 0 mg rahlcr 32 mg Il)l) mg 3-' mg 40 mg 50 mg 32 m g 16 mg 3'_5 mg 32 mg 1(l0 mg 32 mg 30 mg 32 mg 60 mg 32.5 mg 32 mg 15 mg 32 mg 32 mg 32 mg 66 mg 16 mg 32 mg 30 mg 32 mg 0 mg 0 mg 0 mg 0 mg 30 mg 100 mg 100 mg 100 mg 250 mg 200 mg ISO mg t00 mg -50 mg 140 mg 150 mg 150 mg 100 mg 200 mg 200 mg 200 mg Jrar 25-35 mg

I I I I I I I I I I I I I I I I 1028 DRUG DEP£NDENCE / t:HAPTER 22 TAHIf 224-2 Pharmacolo9rca) Actions of Cafteine and Clrnical Features of Caffeinism Anur rlwtrJ Pnurmac uhIRrc a1.1 clrnns Central nmous s)stem Concx Ckarer thoughts Dccrcascd dr ousrncss Sustained tntcllectual cfTon Dim n shcd reaction time Increased motor acti%tt% Medulla incrcascd resprratorn rate and depth Decrcased hcan rate. constnctron of s%stemtc ~asculature Spinal cord Increased re(lex excttahrlrt% Cardro%ascular ssstcm Hcan Incrcasrd rate and force of cotttraction Drlauon of coronarn artcnn Ctrculation D,latton of pulmonarn and general sNstcmic %esscls Gastruintcstinal sNstcm Incrcascd %olumc and acrdrt\ of pastnc sc•mtions Pr ssrf / SrJr E.r1,•,rk On.1 Tuv, ,tlwura'%1ulnIn% (C allrrr,n»r Sctondar\ to tosicit\ Restlcssness. ner. ousness Imuhrln~. ag tatron Tremulousnnso refles h}pcrcxcitahilit.~ Insomnia Headache Senson drsturhances (h~pcresthesia, nngsng in cars. flashes of light. dn mouth, ocular d~sl.rncsras) Tach}pnca Muscle twitching and fasciculations Lctharg~. fatigue. \aunrng (hrphasrr reaction to large duscs) Dcpression Sccondar\ to withdrawal Headache Imtahilrt\ Inahilit\ to Mor1, efccti~cl\ \errnouincss. restlessncss Lctharg~ Palpitations, cxtrisystolcs, tach%cardra flushrng Marked hyrotension and ctrculator\ farlurc (%er\ large doses) \ausca. \omit ng. diarrhea Eprgastnc awarcncss and pain Pussihle peptic ulcer Hcmatcmcsrs Renal systcm incrcascd production of unnc Basal mctatx)lic s\stcm 10 Io ?5 percent tncreast from 0.5 g Miscellaneous to 45 minutes later. The pharmacological half-life is approx- imatcl~ 3'.: hours. Smoking appears to incrcasc the clearance of eaffeinc. perhaps contributing to the higher consumption of cofl'cr h\ smokers. Cafi'c•inc's t\pical actions begin after 50 to 200 mg ha.e bccn ingcstcd. Of epidemiological significance. this dosagc is surpassrd dail\ h) millions. For example, four cups of fresh- dnp. strong coffee: two headache tablets that contain caffeine: and a cola drink amount to a dail\ intake of about 600 mg. Although tolerance has been disputed. it clcarl~ exists -on a clinical basis. e\plaining wh\ some indi~iduals regularl\ con- sume doses of '•CKK) to 3.000 mg a da~ Khile still den\ing problems. Caffeine is relatisels safe. principzll\ tceause it is t~picall. con.umrd tn marl.rdls diluted form. A5out 8 to 10 g- equt\alcnt to ingesting 75 to 100 cups of brewed coffee- µoul,i hc• required for a lethal dosc. ` Neuropharmacolo9Y Neuropharmacological effecu of caf- feinc are not completel\ clanGed. but the following efrecu undouhtedl\ contribute to ps~chiatric manifestations: (1) a significant increase in norepinephrine excretion: (2) sensiti- zation of central catecholamine postsNnaptic rceeptors. partic- ularl\ those for dopamine: (3) a modification of calcium metaholism; (4) possible alterations of c}clic adenosine 3',5'- monophosphate (c.clic AMP) and c\clic guanosine 3',5'- monophosphate (c.•clic GMP); (5) possible a)teration of ace- t~lcholtne and serotonin turno%er and receptor functions: and (6) inhibition of the C'\S effects of adenosine or other endog- Dturrsis DchNdratton Edema Fe~er enous purines, or compctiti%c antagonism of naturall~ occur- ring bcnzodiazepinc receptors. These latter actions are espccially intcresting. because in- vestigations into the nature of benzodiazepinc receptors scr- endipitousl% focused greater attention on caffeinc. Specifl- call\, bcnzodiazcpincs appear to induce their therapeutic ef= fecu through interaction with a high-afTinit% binding site in the brain. probabl~ b} enhancing the CNS inhibitor\ effects of -y-aminobutyric acid (GABA). This same benzodiazepinc receptor seems to interact with endogenous purincs, perhaps inosinc. h%poxanthine• or adenosinc. These punnes are chcm- ica)I, related to caffeine, which appears to competiti%cl~ antagonize the benzodiazepine receptor, possibly explaining its anxiet~-inducing actions. Recent findings, hoµcser, reinforce the s•ieMpoint that the neuropharmacological actions of coffee and tea may not be due solel~ to caffeine or other xanthines and that other components also need to be investigated. For example• coffec has been reported to ha~e opiate receptor antagonist activit~, but this action was clearl~ separable from the eaffeinc in coffee and was not found in tea• cocoa. soup pov,ders. stoclk cubes. or yogurt. The noncaffeinc component of coffee re- sponsible for this action still is unidentified. but it has a molecular weight of approximately 1•000 to 3.500 and is unlikelti to be a peptide. !f confirmed, such a finding would indicate that coffee drinking ma~ induce certaiD effects b} ehanges in opiate rrceptors. Such neurobiological complexi- ties perhaps contribute to indi.idual differences in scnsitivit~ to coffee and tea products. Changes in receptor numbcrs•

I ~ I I I I I I I I I I I afiinitics. or balance-for example, superscnsitiNity or down- rcgulation-also may help explain uhy some individuals re- pon alterations in their tolerance to these bescrages afttr years of apparently uncomplicated consumption. CLINICAL FEATURES The only theoretical requirement for the dc%clopment of caffeinism is the ingestion of adequatc doses of the drug. As shoµn in the nght-hand column of Table ?'.4-?, the symptoms are best understood as dose- relatcd extensions of the drug's routine pharmacological ac- tions. Scnsttivity to different doscs in different persons vancs significantly. and onset tends to be unpredictable and usually insidious. Clinical experience suggests that. among most per- sons. intake of 500 to 600 mg of cafftinc a day represents a standard cut-off point. Exceeding this Ie%cl significantly in- crraus the nsk of de%eloping o~ert clinical manifestations of caffrinism. Although different symptom constellations usually coexist to x>mc drgrre, they will bt discusxd scparately. Anxiety manifestations Diuresis, restlessncss, tremulous- ness. h~pcracti~ity, and irritability are most frequently re- poned. Patients often describe the constellation vaguely-for example, "I've been extremely tense, restless, and jittery latelv.° Other symptoms include dry mouth (perhaps corre- lated to caffeine's effect on the CNS's cholinergic function), sensor) disturbances, hyperesthesia. ringing in the cars, ocular d~skinesias, and flashes of light. Biphasic actions are also common, with some persons describing anxiety at a point when caffeine levels are still rising but later complaining of lethargy and a%ague sense of fatigue. Boulenger and Uhde recently shoµrd that caffeine-induced anxiety effects and rating scale scores were greater in patients µith diagnosed clinical anxiety than in matched normal controls. suggesting that an increased sensiti% ity to the effects of caffeine may exist in anxious patients. Among children and adolescents, the anxiety effects of caffeinism may mimic hy peracti~ ity, despite the paradox that caffeine has been reponed to be possibly therapeutic for mild cases of childhood hyperkinesis. Phar- macological trials with caffeine suggest there are no marked differences between children and adults in objecti.e psycho- motor actions: hoNrver, for an unknow n reason, the only side effcrt reported by children was a tendency to feel nervous, whcrcas more adults complained about side effects, and their complainu wcre more disturbing to them, Psychophysiological manifestations Physical complaints -headache, tach~cardia, diarrhea. Ietharg\, tremulousness, and epigastnc pain-predominate in general medical settings in patients with caffeinism. Paradoxically, attempts at self- medication may accentuate or perpetuate the symptoms, because many over-the-counter products contain caffeine. .Although some studies still disagree, many reports suggest that coffee drinking increases plasma-free fatty acids and low- density lipoprotein (LDL) cholesterol levels, especially among high coffee consumers who also smoke cigarettes. The long- range public health considerations of these effects are un- know n. Insomnia Sleep disruptions have long been obscr.ed in sporadic or moderate users µho consume caffeine near bed- time. In doses of 200 to -tiXW mg at bedtime. caffeine produces an abnormally long latency to the onset of sleep and a shifting of stages 3 and 4 to later in the night. High consurners-those users exceeding 500 to 600 mg per day-usually claim to ha~e tolerance to these side effecu, even when objective testing confirms insomnia or decreased sleep efTiciency. High Soct/on 22.4 / CAFt:EUiE Mq TOee.CCO DEPEKDEr+CE 10'9 caffeine consumers rcport significantly grcatcr use of sedativa hypnotic agents, perhaps because of the way caffeine rn(lu- ences sleep pattcrns. Withdrawal symptoms Electrom~ographic (EN1G) studies showed that regular consumers of caffeine had higher muscle tension than low caffeine consumers after 3 hours or more of abstinence. Even a brief abstinence may produce anxiety in the substantial users. The most common %;ithdrawal manifestation is the caffeine uithdrawal headache. Reported by as man. v as one-third of moderate and high consumers if their daily intake is inter- rupted. this headache seems to be remarkably consistent in different persons. It is described as generalized and throbhing- proceeding from lethargy to a sense of cerebral fullness to a full-blo,An headache. It occurs about 18 hours-approxi- mately five pharmacological half-lives-after the discontin- uation of habitual caffeine intake and respunds best to a rencµrd elc%ation of caffeine plasma Ie%els. perhaps explain- ing µhy many tension hcadachc-prone persons prefer over- the-counter analgesics that contain caffeine. Other with- draual symptoms include drowsiness and Iethargy, rhinor- rhea. a disinclination to µork, irritability, ncnousness, a %aguc feeling of depression, and occasional yaAning and nausea. Depression Sur.cys of psychiatric patients rc~caled that the highest caffeine consumers (more than 750 mg dailN) reponed significantly greater scores on the Beck depression scale than did moderate or low consumers. Bipolar 11 depressi~es re- ported greatest intake. Twenty-two percent of high consumers stated that caffeine makes them "Iess depressed," suggesting that certain depressed patients may be stlGmrdicating with caffeine. Perhaps this tendency to self-medicate explains µhy depressed patients uith hypcrsomnia and anergia wcrc re- poned to consume larger amounts of caffeine than patients without this profile, occasionally producing a"masking efTect" of their clinical features. Further research is required to eval- uatc uhethcr the drug may ha%e a causal relationship Kith depression, perhaps comparable to chronic amphetamines or cocaine use. OTHER FEATURES Accentuation of stress Symptoms of caffeinisrn may intenwine closely with stress manifestations in certain persons. lndi~idualswho consumed coffee while in the midst of recent stress (a job loss) had significant increases in urinary 3-methoxy-4-hydroxyphenylglycol (.%iHPG) Ie~els that µere greater than when they consumed coftet at non- stressful times and greater than the levels in unstressed control groups. lronically, many high consumers report that their caffeine intake actually increases when stres.ud, probably accentuating the psychophysiological manifestztions. Exaeerbation of psychosis Scattered reports have sug- gested that caffeine toxicity may induce psychosis in suscep- tible persons or may exacerbate thinking disorders in patients pre,.iousl. diagnosed as ha%ing schizophrenia. Although these rcport_s are not adequately confirmed µith systematic studies, possible mechanisms for this claim may include modification of catecholamine receptor sites and various neurotransmitter activity levels, especially dopamine. In support of this pros- pect. a cross-over trial among hospitalized chronic psychiatric patients involved substitution of dccaftcinated coffee for caf- fcinated coffee, and there v.ere significant decreases in psy- chotic features-mcasured with the Brief Psychiatric Rzting Scale (BPRS}-during the time pcriod when the decaffeinated product was being consumed. I

I I I I I I I I I I I I I I I I I I I 1030 oRUG oevereofNCE / aWrea 22 Miscellaneous medical issues Caffeine excess ma~ induce or complicate gastrointestinal, cardtac. and renal conditions and is espcciallN contraindicatcd in persons with peptic ulcers, recent mNocardial infarctions, and impaired renal function. High caffcine-consuming collcge students are reported to ha~e lower academic performance than loH consumers. The drug has trcentlN been associated with dvclopmcnt or acccntua- tion of restless legs stindrome and fibrocsstic breast disease. When consumed b) pregnant womcn. it ma% induce impaired fetal doelopmcnt, as Kell as loµer binh weight. Because of possible animal teratogenic effccts, the Food and Drug Ad- ministration proposed to remoNe caffeine from its list of substances classified as Generall% Recognized as Safe (GRAS). A dc, clopmcnt apparcnth groµing in populantN is that raf- feinc has becomc a major component of o%cr-thc-counter dict pills. The efficac} of this approach is quite questionable. An~ Meight loss from such products is probahl% attnhutable largel} to caffeine's diuretic actions (in.ol%ing inhibition of renal tubular absorption of sodium). Such a pattern should not be encouraged. Drug-drug interactions Both coffee and tea have becn re- porled to form an insoluable precipitate with a%anct} of antips~chotic drugs. possihl} intcrfcring with drug absorption. Caffcine also has been suggested to enhance the hreakdoµn of neuroleptic drugs in the hepatic microsomal enz\mc s\s- tem. Although there is no uni.ersal agreement about such efkcts, drug-drug interactions are potentiall,% important and suggest that caffeine products should be used minimall} in patients trceising antips~chotic medication. When caffeine is combined w•ith monoamine oxidasc inhibitors (i\1AO1's). pa- tients ma~ experience increased jittenness. excessi\e irritabil- ii.s. and dtfficult~ in sleeping This effrct ma% be correlated to intcracti~c effects on scrotonin mctabolism. Undesirable s~n- erg.istic intcractions bctKcen caffeine and lithium may dc\elop and further alter renal function among high caffeine con- sumers bcing treated with lithium salts. h1eth)I xanthincs haxr been reported to increase the car- diotoxic potential of d-adrencrgic agonists, such as isoproter- cnol, resulting in a higher incidence of cardiac arrhylhmias. Anecdotal reports also suggest that coffec has been consumed %kith trihexyphcnid\ l to apparcntl5 induce euphoric or hallu- einogrnic statcs. This pattern is potentiall% important for ps~chiatrists bccausc of their widesprrad use of trihexyphen- id~I and other anticholincrgic (antiparl:insonian) products. Interference with lat>oratory tests High doses of caffeine ma% interfere %kith dcxamethasonc suppression tests (DST's). CafTcinc µithdraAal produces large incrcases in urinary MHPG Icscls. thus interfering %kith interpretation of this test. Finall\, eaficine has becn shown to alter the phase of circadian rh\lhms. now l.nown to haxc importance in the interpretation of most physiological variables. Interactions with other psychotropics Unfortunatcl\, caf- feine intake is highl\ confounded %kith other substance use: highest consumers report significantl\ greater use of minor tranquilizers, stdati~e-h\pnotics. alcohol, and cigarettes. This fact ma\ complicate the clinical presentation. Validity of utfeinism The clinical x•alidit\ of cafTcinism has been strengthened b\ laborator\ induction of the s~ndromc and b\ repeated obser\ations that the s)mptoms disappear Mhcn the drug is withdraNn from afflicted subjects. Further- more, after abatement of s,.mptoms. a caffeine challenge tends to reproduce them again. The American Council on Sciencr and Health rtccntl~ rcvicwrd a~ailablc scicntiGc literature and concluded that eaffeine, as generall\ consumed in doses less than 300 mg/daN, is not a threat to the health of most Americans. but that doses abo~e 600 mg/da\ ma~ cause serious health problems. The s\mptoms of caftcinism are lisied in Table 22.4-3. COURSE AND PROGNOSIS The longitudinal course of caffeinism is unpredictable but generall~ insidious. Tolerance maN de%clop at different stagcs, producing temporar\ s~mp- tom disappearance, but if intahe is again increaseds s~mptoms tend to reappear. In the absence of other ps~chiatric conditions, the prognosis for caffeinism is good. Permanent long-term ps\chtatnc con- sequences ha\c not been documentcd, and afflicted persons gcncrall~ function wcll in most areas. DIAGNOSIS The diagnosis of caffcinism depends pnmanl\ on a specific and detailed historr to confirm significant caf- fcinc intake and the characteristic clinical profile. Caffeine questionnaires are helpful. Caffeinism should specificall) be suspected in all patients prescnting %kith anxict\, sleep dis- turbances, ps}choph\siological problems, and atypical anx- ious depressions. A high index of suspicion should exist for patients who do not respond as expected to anxiol5iics and sedati~e h~pnotics, all patients with recurrent headaches re- sponding best to analgesics containing caffeine, and o\cracti~e children. The diagnosis should be tentati.e until it is cltnicallN supported b} a period of caffeine Kithdra%kal followed h~ s\mptom relief and, ideall}, b\ a caffeine challenge (A-B-A design) to reproduce the symptoms and aid confirmation of a causal relationship. After intake is stopped or dramaticall\ reducrd. troublesome symptoms should bcgin clcanng in 4 to 10 da\s if the\ are due to caffeine toxicit~. TAet f 22.4-3 Catlemism Confirmcd histon of recent caficine consumption, usuall~ excced- ing'50 mg a 6}. more often exceed ng 500 mg a day Presence of at least fi~e of thc follo%king s\mptom constellations at a time %.hcn eafTeine is being consumed: I. Restlessness. nmousncss. imtahiltt%, agitation, tremulousness, muscle tµttching. or fasciculation 2. Insomnia or sleep dtsruption 3. Headache 4. $cnsor, dtsturbances (h\pcresthesia. ringing in ean. Itghthcad• edness, flashing of Itght. ocular d)sktnests) 5. Dturests 6. Cardto~ascular s)mptoms (palpitations. cxtras~stoln. arrh~lh- mtas. flushing, uch~cardta, mcreased cardtac aµarencss) 7. Gastrointestinal complaints (epigastnc pain, nausca. %omtung. diarrhea) 8. Rambling t1oM of thoughts and saeech. periods of tnexhausta- biht\ Persistence of symptoms da6 or sporadicall~ for at least 2 Mecks in conjunction ~.tth caffeine consumptton. or consistcnt dc%elopt ment of such symptoms each time higher pfktne consumption occurs Absence of an% disorder that otherNise accounts for the s%mptoms of afTetnism. such as anxiet\, h.penh~Toidtsm, phcochromoc.- toma. mania, hypomania. and elcctrol.le dtsturbances: cafTctntsm ma~ contnbute to and aggra.atc thesc conditions Onset of afTetne withdnwal s\mptoms follov, ing cessation of caf- feinc intake after a prolonged period of consumption wtth at Ieast three (probable) or four (definite) of the folloMtng signs and s~mptoms present: 1. Hudache, being rclte%ed b~ funher caffeine inuke 2. Imubtht} 3. Inabtltt\ to work cficrti~tly 4, t:er•ousness 5. l.etharg~ 6. Yawntng

I I I I I I I I I I I I I I I I I I The differential diagnosis of cafT'etnism should include anx- iets disorders, mania, hypomania, hyperthyroidism, pheo- chromocytoma, elcctrolyle disturbances, spontaneously oc- cumng sleep disorders, and intoxication from cocaine, am- phctamine. and similarly acting sympathomimetics. Caffein- ism may also coexist with and complicate these entities. TREATMENT Effcc-tive treatment depends principally on the discontinuation or reduction of caffeine intake. Because users often express profound skepticism µhen told that caf- feinism may be contributing to their symptoms, patient co- opcration is not always guaranteed. Participation by family members may be helpful. The substitution of decaffeinated be~eragcs and the en- couragement to consume water when thirsty impro~es out- come. The use of anziol.-tics should be a~oided if possible. Patients should be cautioned about the substitution of other herbal preparations. because these preparations ha,.e been rcportcd to induce their oun types of psychiatric symptoms in some consumers. With increased asailability of decaffein- ated bc%cragcs, there noµ is considerably greater flexibility in searching for altcrnatisc bescrages. Long-term data are not yet available to confirm the degree of change in patients treated for cafTeinism. In the author's ctprricnce, about one-third of afflicted patienu maintain muderate or no cafl•eine use µithout difficulty. but the major- ity episodically resume pre%ious patterns of high consumption and de%elop fluctuating patterns of symptom recurrence. TOBACCO DEFINITION AND HISTORY Tobacco dependence is de- fined in the third edition of the Dtuennstic and Statistical .tlunuul (P/ tlrntul Disorders (DSM-111, 305.Ix) as persistent tobacco use for at least I month, dcspite the person's psycho- logical distress at the need for repeated use, or persistent tobacco use Mhrnner a person has dneloped serious tobacco- related physical disorders. Tobacco withdrawal (DS!st-I11, 292.00) is defined as a phNsiological wtthtirawal syndrome that is precipitated by the crssattun of chronic tobacco use and that is characterized by a strong cra%ing for tobacco, anxiety, irritability, impaired attrntion. a cogniti.e preoccupation with actions associated with tobacco use, and mild physiological alterations. such as restlcssness, headaches. drowsiness, and gastrointestinal dis- turbancts. N'ithdraHal from the nicotine contained in tobacco is prrsumahly responsihle fer most facets of the withdrawal syndrome. Columbus introduced tobacco to Europeans after his contact with the Indirns of the Canhhran. Drspitc histoncal attempts to legalls han thc substanic, the drug gtew in populants. especially after the introduction of paper rigrn and crgarcttc-mai.ing marhrncs in the m d•lyth ccntur.. \iiotinc was is.ilatctif from the ka%es of tohacco cls earl) as I!t_R and is now recog.niied as heing rcsponsihle for many, hut rcnatnl~ not all. of the pharmacolog.ical etkcts of tobacco use. There .tre apprusimatel% 15 other mator touc agents in the gas phase of rigarctte smoke and more than ?0 in the particulate matter. Few t+f tht•se toxic agents hate hrcn studied adrquatcly. In thc c.uk Iyh(h, a committee of I I sttcnusu appointed by the Surgron C;cncral of the l'nitc-t1 Statcs rettcMed e.tcnsite studies and k,~n, IuJtti that cscrssr.e tobacco use isan imponant medical haurd. In Nn5, the United Statcs go\ernment mandated health warnings on rigarette cuntainers; in 14'0. gotcrnment officials banned cigarette jJtcrt ang from radio and tclcttswn. The (rcq uencz of cigarette .m,,l,ing on prime-time teletis+on hss dropped 10-fuld oter the past thrd• decadcs. Antismoking urganvatioms also became more militant tn oprxhrng tobacco use and promoted legtslation that restnctt smok- rntc ,rrc.u. the evonomic cunsiderationst huMeter. that are associated Mith tohact•u growing inctttahl% cun(lict wtth public hcalth cffuns to Jimn .h tobacco use. EPIDEMIOLOGY Approximately 60 million Americans .mokr more than 200 ts pes or brands of cigarettes and spend s.amon zz 4 / c.FFEr+e a,ro Ton..cca oer£roeNCE 1031 more than S23 billion annually in the process. More than 35 percent of American men and approximately 30 percent of American women smoke. Although the percentage of smok- ing adults has been decreasing. the percentage of women and teenage smokers unforYunately. increased in recent yeari. Prr- dictably, deaths from lung cancer in women simultaneously increased, becoming the number one cause of cancer deaths in women, recently exceeding deaths from breast cancer. Sixty-fi.e percent of physicians smoked tobacco in 1950; by 1975, this number had decreased to 17 percent, and a scant 5 percent of pulmonary physicians repoRed smoking in 1983. Sur.cys re~eal that 80 percent of all adult smokers indicate that the) would like"te quit; 75 percent ha, e tried to cut down, and 60 percent hase attempted to stop but hasc failed. The number of persons Kith persistent use despite tobacco- induced physica) health problems is unknown. Cigarette smoking was implicated in more than 320,000 deaths in 1977, howc%er, and because many still used tobacco at the time of dcath. the problem certainly is of staggering proportions. The incidence of tobacco withdrawal is impossible to estimate. CAUSES The initiation of tobacco use seems to occur pre- dominantly through social reinforcements. Almost 9 out of every 10 teenagers who smoke repon that at least one of their four best friends isa rcgular smoker. tionsmokers ha~e exactly the opposite pattern. Cigarette smoking among teenage girls tends to be associated with other btha.ioral patterns consid- ered rebellious. For example, 25 percent of teenage girl smok- ers reported they also used marihuana, compared with similar usage by only 3 percent of nonsmokers. Stress also appears to be a factor in tobacco use, since habitual cigarette smoking was positiNely, associated with high stress Ie%els, an effect similar to that obsrr.ed with caffeine. Once smoking is started, nicotine's multiple pharmacolog- ical effects promptly produce habituation in most regular users. Tobacco also may induce a conditionin of the spccial senses, especially thosc of smell and taste.[nstruments of smoking appear to function as psychosocial coping mecha- nisms for some smokers: the physical actions of holding the cigarettes or cigars or pipes, tamping the tobacco, striking matches, inhaling. and exhaling enable some persons to feel - comfortable in stressful situations. In addition, once starxed, many smokers state that they avoid discontinuation of their habit because they fear weight gain, CLINICAL FEATURES Tobacco dependence Psycho- logical distress at continued tobacco use usually presents %kith mild anxicty. subtle guilt or shame, the dnclopmcnt of a secreti~e pattern of tobacco use, or the appearance of an angrv, counterattacking stsle that defends the substance and criticizn opponenu. If physical disorders exist that may be correlated to tobacco use. diagnosticians are forced to make a judgment whether the drug is causati~e or exacerbating. Consultations with other physicians treating these conditions may be ncccssar. before applying this diagnosis. Because cigarette smoking has now been documented to pose a major health hazard for women who use oral contracepti~,es, they should be considered a special high-risk group. Tobacco wftdrawal The most common symptoms of to- bacco withdrawal are irritability, restlessness, dullness, slecp disruptions. gastrointestinal disturbances, headache, impaired concentration and memory, anxiety, and occasionally an increased appetite. Increased slow rhythms dnelop in the electroencephalogram (EEG) after discontinuation of to- bacco. Also seen are dccreased heart rate and blood pressure, incrcased frequency of muscle contractions, reduced perform- I

I I I I I I I I I I I I I I I I I 1032 oauc DEP£NOt°.NCf / c.•+APr£a 22 ance on vigilance tasks. and Mcight gain. The sense of craving for tobacco steadil} increases in the first µrek after tobacco discontinuation. Other clinical considerations Another efTert that clinicians ma% encounter is acute nicotine poisoning s~ndrome, con- sisting of nausea. sali%ation, abdominal pain. %omiting or diarncea, headaches. dizziness. and a cold sµcat. lnahilit% to concentrate. mental confusion. %anous senson disturbances. tach%cardia, and a weak, rapid pulse oftcn are present. Pre- natal exposure to nicotine ma~ be associated with reduced birth weight of the fetus. Clinicians must consider the fact that tobacco use ma,. complicate prescribed ps~chiatric treatmcnts. Because the substance increascs the function of drug-mctatwlizing en- z%mes, lower plasma lc%els of neuroleptics and tnc~clic anti- depressants ma~ result. This effect ma% explain Kh} smokers who take chlurrroma7inc. for example. ha%c loµer rates of sedatton and less hypotension than do nonsmoken. Presum- ahl~. an unknown percentage also ma% ha%e inadequate ther- apeutic effects. ~ Tobacco use is highl% confounded with the use of other psyrhoactive substances. Alcoholics. for examplc, smoke sig- nificantl} more than do nonalcoholtcs- and there is a high positive correlation between the amount of alcohol consumed and the amount of tobacco used. These correlations begin earl% ; adolescent smoken ha, c bccn obscrNed to dnnk more beer, w•ine, and liquor than do nonsmokers. Tobacco use also correlatcs positi%el~ w6th higher caffeine use. The essential features for the diagnosis of tobacco with- drawal are listed in Table 22.4-4. Personality factors Smokers rcponcdl~ differ from non- smokers in being somewhat more impulsi%c and externalls oriented and having a higher degree of extro~crsion, more antisocial beha%ior, and greater levels of anger. Htghcst smok- ing rates are ohscrned in persons who atc divorced and separated. Lowest ratcs occur in persons Mith a higher than a%erage education, in persons in a high socioeconomic Ie%rl, in mcmberz of selected religions, as well as in physicians. TAFit 1 22 4-t Essenual F.atures of Dependence and Tobacco Withdrawal TotvLco dcprndrnLY Confirmed historN of mcent tobacco use, usuall~ exceeding one- half pack of ctgarettes a da\ or the equi.aleni in other forms of tobacco for at'cast I month The presence of at least one of the folloMing I. Senous attempts to stop or significantl\ reduce the amount of tobacco use on a permancnt basis hi%c been unsuccessful 2. Attempts to stop smoking ha~e led to the de%elopment of tobacco MithdraNal (see below 1 3. Indr\ tduals conttnue to use totucco despite a serious phsical disorder. such as emph,%scma or cardio\ascular discase. that the\ know is exacerbated by tobacco use Tobacco Mithdnwal Confirmed use of tobacco for at least se~eraJ Mecks at a level equisalcnt to more than 10 cngaretin a da\, with each eigarettc containing at least 0.5 mg of nicotine Abrupt cessation or almost complete discontinuation of tobacco use. followed within 24 hours b~ at teist four of the folloMing: 1. Cn%rng for tobacco 2. Imuh,ltt} 3. Anxtet~ 4. Impaired concrntration 5. Restlessness 6. Headache 7. DroMvness 8 Gastrointestinal disturbances (6-96 hours aficr cessation) COURSE AND PROGNOSIS Tobacco dependence has no precise age of onset or longitudinal coursc. B\ definition. tobacco disordcrs ma\ penodicall~ disapfxar and appear. The tobacco withdra>aal s\ndromc de\clups earl\ in most modcrate and hca\-\ smokers with discontinuation of tobacco usc, occasionall\- as soon as 90 to 120 minutes after the last use. S~mrtoms usuall\ persist for se%eral weeks. but plague some indi\iduals for months or e\en \cars in some sok•tal settings. The degree of ps~chiatric impairment fromiobacco disor- dcrz is usuall~ minimal, hut some pctsons expencnce signifi- _cant impairment dunng µithdraHaT~his discomfom crnainl\ eontrihutes to the finding that onT7atxout onc-quaner of the indt~iduals who attempted to stop smoking ha~c succeeded at the end of I year. Bccause these diagnoses are often o~crlociked. omittrd, or idcologicall~ opposed. incidence and pn•salcnre figures must br interpreted Kith caution. TREATMENT Multiple approaches ha\c hcen prupx)k•d to stop smoking. and there has been a recent prultl'eration of clinics claiming to aid in this task. Although compansons are unatiailahlc or inadequate, the most effective treatments ap- pear to depend on accurate information, the w-oidance of moralizing and judgmental stances. and the use of undcr- standing. supportise but firm approaches. ti1'nttcn contracts for the discontinuation of tobacco use ma\ bn helpful. The substitution of other acti\ities dunng times when cigarettes are traditionall} smoked ma\ pro% ide di%crsions. Daily rclax- ation techniques ma\ help. Smoking paraphernalia and all available sources of tobacco should hc climinatcd. Support from friends.+ho have succeeded in quitting the habit should be encouraged. People who have successfull\ discontinued smoking wcre significantl% more likel~ to ha%c presented thcroscl~rs to a smoking cessation program because some significant other wantcd them to stop. Positivr reinforcement from treating clinicians has been found to be espcciall\ in(lucntial, sup- porting the importance that the ph}sician be a nonsmoker. Most cigarette smokers unfortunatel} state that thc\ have nner been advised b\ a ph) sician to discontinue their smok- ing. The doctor might also suggest that mone~ prc\ iousl.\ used for tobacco be allocated for some pleasure. such as a desired vacation or luxur\ item. Hypnosis, ad%ersi~c condi- tioning-such as rapid puffing to develop nicotine toxicity- and phased uithdrawal plans all have been used. Nicotine gum and nicotine spra\s can be substituted for the nicotine contained in tobacco, but it is doubtful that the; facilitate long-term discontinuation. In the 1980s. media a6enise- ments began to promote chewing tobacco, and in some Amcr- ican communities use has become widespread. Because of risks of oral cancer and other consequcnces, such a pattcrn seems simpl\ to produce a different set of medical concerns. It should not be encouraged as an alternative to smoking. Clinicians must anticipate that repeat efforts ma\ be ncc- essar~ . Also. many people wfio fail to respond to one approach ma\ benefit from another. Outcome of tobacco cessation efforts is unpredictable. People who successfull\ quit smoking are generall~ older, smoked less often throughout the da} and evcning. and smoked less in social gatherings. The National Commission on Smoking and Public Policy conducted a 5-year folloµ-up of participants in the most successful smoking-reduction programs and determined that 18 percent had succeeded completcl~ in their cessation efforts. Of those who continued to smoke, nearl\ one-half were smoking less than before they entered the program. No treat- I

I I I I I I I I I I I I I I I I I mc•nt method•scemcd to be significantl~ superior to others. These figures indicate that current treatments are beneficial for man~, and that nihilism is unAarranted. They also docu- ment the distinct need for better approaches to impro~e these outcome figures. SUGGESTED CROSS REFERENCES Alcoholism is discussed in Section 22.3. Opioid dependencc and dependence on nonnarcotic agents are discussed in Sec- tion 22.1 and Section 22.2. respccti%cly. Organic mental disorders induced bs drugs are discussed in Chapter 19. REFERENCES BuuhliA J H. Quinn M J. Clements J A. Henngton A C. W~nne K N. Funder J%k: CofTee contains potent opiate rrceptor binding aiU%tt~ Nature 301 246. 1993. BBoulenger 1-P, L'hde T µ': Caffeine consumption and anxiet}: Prc- Srdan 22 I/ CAFFEN'E Al'D TQ6ACCO DEPENOEMCE 1033 Itmrnan results of a sur.e} companng paticnts with amiet~ dis- orders and normal controls Ps~,:hopharmiroI Bull l,t' 53. 1 aK2. Dretshaeh R H. PfcilTer C: CalTeine-MtthdraµaJ hcadache. 1 Lab C7in Mcd :d 1212. IVS3. Dunn µ' L. Jr. editor Smnl rne B'hJsuir ,1l,Hnrs and ln,rnrnes 'A 1nstWn & Sons. \Vashtngton DC. 1`773. Goldstcin A. Katrcr S: Ps~chutrop c cffects of ca(Tcinc in man fli A questionnaire sur\e} of cotTee dnnlcrs and tu e1TcYU in a gtoup of housewi\es. Clrrt Phannacol Ther /U 477, 1969. Greden 1 F: Anviet} or iafTeinism: A diagnostic dilemma. Am 1 Ps~chtatn, Ijl IUb9. 1973. Greden 1 F: The tea contro%en~ in Colonial Amenca J4M 4 'jA 53. 1976. Gralcn 1 F: 4rniet} and deprcssion a_suxiated wuhca(Teinism among A ~chiatnc inpatients. Am J Pscchtatn 135 1463, Ia7R. J H. Kantler M: \teottne: Tuhjccu use. ahuse and dcprndencY. In Suh,runre ahtcst C'ltni-ul Pnohh'nr% and Per%r,•,tni•~, J H Le~- inson. C Ruir. editors. p'56 1i illiams SWill.ins. Bdltimore, 1148 1. L'nited States Puhltc Health Sersice. Smokrn¢ and llwlth Reporr ol the.aJ~ n~rt' C'~mmrlt~'~'tu ih~'.Su!e~' n cirn~•r~l ~!7/t~ l't~hh, llr~/f1t Srnrre. USGo%ernment Pnnt ngOfTice, µ'ashingtun tX-. 1964 \A, eiss B, Laties V G: Enhank:cment ut human perlorrnuncY b} caffeine and thc amphetamines. Pharmacol Re% 14 I. 1y6'.