craving models and implications for treatment_anton

What Is Craving?

Models and Implications for Treatment

Raymond F. Anton, M.D.

Although many alcoholics experience craving, researchers have not yet developed acommon, valid definition of the phenomenon. Numerous models of the mechanismsunderlying craving have been suggested, however. One of those models—the neuroadaptivemodel—suggests that the prolonged presence of alcohol induces changes in brain-cellfunction. In the absence of alcohol, those changes cause an imbalance in brain activity thatresults in craving. Furthermore, the adaptive changes generate memories of alcohol’spleasant effects that can be activated when alcohol-related environmental stimuli areencountered, even after prolonged abstinence, thereby leading to relapse. Similarly, stressfulsituations may trigger memories of the relief afforded by alcohol, which could also lead torelapse. Neurobiological and brain-imaging studies have identified numerous brain chemicalsand brain regions that may be involved in craving. Psychiatric conditions that affect some ofthese brain regions, such as depression or anxiety, also may influence craving. A betterunderstanding and more reliable assessment of craving may help clinicians tailor treatment tothe specific needs of each patient, thereby reducing the risk of relapse. KEY WORDS: AOD(alcohol and other drug) craving; neurobiological theory; biological adaptation; reinforcementfactor; AOD abstinence; AODD (alcohol and other drug dependence) relapse; brain function;scientific model; specific AODU (alcohol and other drug use) measurement and test;evaluation; treatment; literature review

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Many alcoholics, includingthose trying to achieve absti-nence, experience craving for

alcohol, often for extended periods oftime. Jellinek and colleagues (1955)first recognized craving as a centralcomponent of the alcohol dependencesyndrome. Up until the 1990s, how-ever, other researchers and cliniciansdid not rigorously investigate this phe-nomenon. Only during the past 5 to10 years has interest in craving increased,fueled to various extents by numerousdevelopments, as follows:

• Cognitive psychology, which hasplayed an increasingly importantrole in the investigation and treat-

ment of alcoholism, emphasizes theneed for understanding, monitoring,and using alcohol craving as part ofa structured alcoholism treatmentapproach (Marlatt and Gordon 1985).

• Researchers and clinicians have re-evaluated classical conditioning1 as a mechanism that may underlie adrinker’s response to alcohol-relatedstimuli, or cues, in the environment(e.g., the smell of beer or the sightof a bar); as a result, researchershave developed hypotheses andexperimental approaches related to

cue-induced craving (Cooney et al.1984; Monti et al. 1987).

• Medications such as naltrexone havebeen found to reduce relapse among

RAYMOND F. ANTON, M.D., is a professorof psychiatry and director of research atthe Center for Drug and Alcohol Programs,Alcohol Research Center, MedicalUniversity of South Carolina, Charleston,South Carolina.

This work was supported in part byNational Institute on Alcohol Abuse andAlcoholism grants RO1–AA–09568 andP50–AA–10761.

1For a definition of this and other technical termsused in this article, see the glossary, p. 172.

abstinent alcoholics, and some stud-ies suggest that these medicationsalso may reduce craving (O’Malleyet al. 1992; Volpicelli et al. 1992;Anton et al. in press).

• Researchers have greatly expandedthe understanding of the brain mech-anisms underlying alcohol and otherdrug (AOD) dependence and of thebrain structures that may be associ-ated with craving (Grant et al. 1996;George et al. 1999).

• Researchers and clinicians havedeveloped improved instruments forassessing the severity of craving; thesenew rating scales have greater reliabil-ity in measuring and defining crav-ing (Anton et al. 1995; Bohn et al.1995; Singleton et al. 1995).

• The methods used in alcoholismtreatment research have becomeincreasingly sophisticated; as a result,the relationship of concepts such ascraving to clinical outcome now canbe reliably evaluated (Roberts et al.1999; Flannery et al. 1999).

Despite the renewed interest in crav-ing, researchers and clinicians have notyet developed a common definition ofthe phenomenon or identified its under-lying causes because craving is primarilya subjective experience for each drinker.Without a valid, uniform definition ofcraving, however, clinicians cannotaccurately assess their clients’ levels ofcraving or measure changes in cravingthat might indicate an improvement or worsening in the client’s condition.The lack of a definition of craving alsoimpedes researchers in their investigationsof the neurological and psychologicalmechanisms contributing to the experi-ence of craving. A better understandingof those mechanisms, in turn, couldlead to improved behavioral and phar-macological approaches for the treat-ment of alcoholism.

This article reviews various modelsof craving that researchers have developedin recent years to explain the clinicalphenomenon and underlying mecha-nisms of craving. In addition, this articledescribes the brain networks that have

been associated with craving as well asthe approaches used to measure crav-ing. Finally, the article summarizes theclinical implications of an improvedevaluation of craving and provides anoutlook on future craving research.

Models of Alcohol Craving

Although the concept of craving appearsto be central to the understanding ofaddiction to all AODs—particularly to the loss of control over and relapseto AOD use—precise definitions ofcraving have remained elusive (Ludwigand Stark 1974; Kozlowski and Wilkin-son 1987; Kozlowski et al. 1989;Sitharthan et al. 1992). Similarly, noagreement exists among researchers andclinicians on how to measure cravingaccurately. Nevertheless, investigatorshave made substantial progress indeveloping numerous models of AODcraving (for reviews, see Singleton andGorelick 1998; Anton and Drobes1998). Singleton and Gorelick (1998)have developed a classification schemethat comprises two general categoriesof craving models: (1) models based onconditioning mechanisms (i.e., condi-tioning models) and (2) models basedon cognitive mechanisms (i.e., cogni-tive models) (see table, p. 167).

Conditioning models are based onthe tenets of classical conditioning.These tenets posit that alcohol-relatedcues (e.g., the sight of a bar or a beerbottle), after repeatedly being pairedwith alcohol consumption, becomeconditioned stimuli—that is, they elicitthe same physiological and psychologicalresponse as alcohol consumption itself(e.g., release of certain brain chemicals[i.e., neurotransmitters]). If alcoholconsumption does not occur immedi-ately, these cue-induced responsesresult in craving, either to experiencealcohol’s pleasant, or reinforcing, effectsor to avoid or alleviate the unpleasant,or aversive, effects of not drinking.Conversely, cognitive models are basedon the assumption that responses toalcohol and alcohol-related cues involvevarious cognitive processes, such asexpectations regarding the pleasanteffects of alcohol and a person’s belief

in his or her own ability to cope withthe desire to drink. Although some ofthese models may be more relevant todrugs other than alcohol, many charac-teristics (and, consequently, models) ofcraving overlap among various AODs.

Despite their differences, all cravingmodels assume that alcohol craving is amultifaceted phenomenon that is influ-enced by a variety of factors. Further-more, animal experiments suggest thatcraving may be associated with certainbrain regions (i.e., neuroanatomy) andneurotransmitters (i.e., neurochemistry).These relationships, however, have notyet been described in detail, and betterclinical and laboratory models of crav-ing are needed to address those issues.Such models likely will improve under-standing of the neuroanatomical pro-cesses involved in craving, as well as ofcraving’s role in abstinence and relapse,and may ultimately lead to improvedpsychosocial or pharmacological treat-ment approaches for alcoholism.

Most researchers and cliniciansagree that a greater understanding of allaspects of craving is necessary in orderto improve treatment. Models thatattempt to merge psychological, behav-ioral, and brain mechanisms may bemost useful for fostering the formula-tion and evaluation of new theories oncraving. The next section discusses onesuch model, which attempts to explaincraving in the context of phenomenafrequently observed by clinicians.Although many aspects of this modelremain speculative and more data areneeded to support the concepts described,the model can help researchers linkspecific neurochemical systems to theprocesses that underlie the manifesta-tion of craving.

A Neuroadaptive Model of Craving

Scientists believe that a gradual and,perhaps, permanent adaptation ofbrain function (i.e., neuroadaptation)to the presence of alcohol is a centralfeature in the development of alcoholdependence (Robinson and Berridge1993; Koob and Le Moal 1997). Long-term alcohol consumption interfereswith many brain functions. Becausethe body, including the brain, must

166 Alcohol Research & Health

maintain a balanced state (i.e., home-ostasis) with respect to critical bodilyfunctions (e.g., blood pressure, bodytemperature, and communicationamong cells), many cells—includingnerve cells (i.e., neurons) in the brain—adapt their activities in response to theprolonged presence of alcohol. Thisneuroadaptation, or sensitization, leadsto certain characteristics of alcohol depend-ence, such as tolerance and withdrawal,as well as to a condition that might be

called reward memory (see figure 1, p.168), a memory that has its roots incertain brain cells and is dependent onchemical changes in those cells. The“reward memory,” which may be uncon-scious, gives heightened attention, orsalience, to environmental cues that arecommonly paired with alcohol (e.g., thesmell of alcohol or the sight of a beerbottle) or to alcohol consumption itself.

Neuroadaptation likely occurs to agreater extent and more permanently

in people who are at increased risk fordeveloping alcoholism, either becausethey have inherited a genetic predispo-sition from their parents or becausethey have acquired such a susceptibilitythrough repeated experiences of severestress. Such stress experiences, whichcan amplify the alcohol-induced neu-roadaptation processes, can be medi-ated either by internal factors (e.g., amajor psychiatric disorder) or by envi-ronmental insults (e.g., trauma or lossof a family member).

Animal models of addiction andcraving (Koob and Roberts 1999), as well as pharmacological studies inhumans, have indicated that severalneurochemical systems contribute toneuroadaptation to alcohol. For exam-ple, the neurotransmitters dopamine,glutamate, gamma-aminobutyric acid(GABA), and endogenous opioids, aswell as the neurons that respond to thesemolecules, may play a role in the devel-opment of reward memory. In addition,glutamate and GABA are thought toplay a major role in alcohol withdrawal.Stress, which may influence neuroadap-tation, also is modulated by neuro-chemical systems, primarily thoseinvolving the neurotransmitter serotonin.Consequently, medications that affectthe serotonin system, such as fluoxetine(Prozac®) and sertraline (Zoloft®), areeffective in the treatment of many psychiatric conditions (e.g., depressionand various anxiety disorders). Thesemedications also have been studied forthe treatment of those conditions inalcoholics.

Given the diverse functions of neu-rotransmitter systems, abnormalities in any of the systems may result in theexperience of craving. In alcoholics,such abnormalities can result fromneuroadaptation to the presence ofalcohol, which occurs insidiously overmany years. In most cases, the drinkeris unaware of the neuroadaptation, and many alcoholics—particularlythose who are in the early stages ofalcohol dependence—are likely to deny any craving for alcohol. In fact,Tiffany (1990) has suggested that crav-ing emerges fully only when a person is prevented from access to AODs orconsciously attempts to quit AOD use.

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Craving Models and Implications for Treatment

Classification of Models of Craving and Their Major Characteristics

Models based on conditioning mechanisms

Conditioned incentive and appetitive modelsCraving results from the desire to experience the positive (i.e., reinforcing) effectsassociated with alcohol consumption; craving may occur in the absence of alcoholconsumption and in the presence of stimuli or situations that previously were asso-ciated with drinking.

Conditioned tolerance modelsCraving results from the desire to avoid the negative (i.e., aversive) experience result-ing from physiological changes involved in conditioned tolerance (i.e., responses tocounteract the effects of alcohol in the brain, which also can occur in the absence ofalcohol consumption in situations that were previously associated with drinking).

Conditioned withdrawal modelsCraving results from the desire to avoid the aversive experience of conditionedwithdrawal (i.e., withdrawal that is induced by stimuli that have been associated withprevious withdrawal experiences).

Autoshaping modelCraving, or the urge to drink, reflects the drinker’s monitoring of internal and exter-nal stimuli that in the past have been reliably associated with alcohol consumption.

Incentive sensitization modelCraving is defined as a conscious experience that occurs when the drinker paysexcessive attention to alcohol-related stimuli or considers those stimuli excessivelyattractive; the attention to or perceived attractiveness of alcohol-related stimuliincreases with repeated alcohol exposure (i.e., sensitization occurs).

Models based on cognitive mechanisms

Cognitive-behavioral modelsCraving is considered a subjective state mediated by the expectation that drinkingwill have positive effects or will improve an existing negative mood state; cravingoccurs particularly in situations where drinkers have little confidence in their abilityto resist alcohol.

Cognitive model of drug urges and drug use behaviorCraving and urges are considered nonautomatic cognitive processes that resultwhen plans for drinking are blocked or impeded; craving is not required for eitherdrinking or relapse to occur.

Neurocognitive modelsCraving influences and is influenced by other cognitive processes; during craving,brain regions associated with affect and memory are activated.

SOURCE: Singleton and Gorelick 1998.

The neuroadaptive model of craving(see figure 1) proposes that differentmechanisms lead to craving during earlyalcohol withdrawal and during laterrecovery. During alcohol withdrawal,brain mechanisms that have adapted tothe chronic presence of alcohol are leftin an altered state (Koob and Le Moal1997). This imbalance can lead tophysiological instability (e.g., anxietyand cardiovascular hyperactivity); sleepdifficulties; and, possibly, subdueddrive or reward states (e.g., depression,lack of motivation, and concentrationproblems). These symptoms are allassociated with a subjective sense ofdiscomfort, which may lead to a desire,urge, or craving for alcohol in order to“feel normal” again. Some of the mech-anisms underlying the craving of earlyabstinence may persist for a consider-able period (i.e., weeks to months). Ifthe person remains abstinent or con-sumes very little alcohol, however, thealtered brain mechanisms eventuallyreturn to their original state, leading to a renewed sense of well-being and a decrease in alcohol craving.

Even people who have remainedabstinent for many months or years,however, can relapse to alcohol abuse.These people often report an intenseurge or desire for alcohol as well asthoughts of drinking that can eitherappear suddenly or increase over aperiod of time. This craving for alcoholthat occurs later in recovery likely iscaused by a long-term recollection of“what it was like to drink.” Situationsin which alcohol previously was experi-enced as pleasurable or in which alcoholpreviously served to relieve stress mayactivate this memory. The conditioningmodels of craving and relapse attemptto explain these situations in the termsof classical stimulus-response relation-ships. According to those models, envi-ronmental events or changes in internalemotional states trigger a series of neu-rochemical reactions that through pastexperience have been programmed toactivate various brain systems, therebyleading to the experience of craving.

Many alcoholism treatmentapproaches attempt to intervene in thisconditioning process and thereby pre-vent relapse resulting from craving

elicited during late recovery. For exam-ple, cognitive-behavioral therapy strivesto provide the patient with cognitivestrategies to manage craving or craving-inducing situations. Treatmentapproaches based on social networks(e.g., Alcoholics Anonymous) attemptto distract the client from craving andenhance his or her resistance mecha-nisms against the phenomenon (e.g.,by encouraging members to call theirsponsors if they experience craving).Finally, “anticraving” medications,which prevent the brain from initiatingor amplifying the craving-related neuro-

chemical processes, are beginning to beused in clinics.

Brain Networks AssociatedWith Craving

Advances in neuroscience, particularlyin brain-imaging technology, are bringingresearchers’ understanding of craving to a new level by beginning to link thepsychology of craving to certain brainstructures. These analyses have led tothe development of a neuroanatomicalmodel that attempts to correlate some


Figure 1 The neuroadaptive model of craving. This model proposes that chronicalcohol exposure leads to changes in brain cell function (i.e., sensitiza-tion, or neuroadaptation) that are expressed as changes in the activity ofvarious brain chemicals (i.e., neurotransmitters), such as dopamine,glutamate, gamma-aminobutyric acid (GABA), and endogenous opioids.Neuroadaptation can contribute to certain characteristics of alcoholdependence, such as withdrawal, and to the development of a rewardmemory—that is, the memory of the importance of alcohol or alcohol-related stimuli to the drinker’s well-being. During initial abstinence, whenalcohol withdrawal may occur, neuroadaptation leads to an imbalance inbrain function, which results in subjective feelings of discomfort and,subsequently, craving. During prolonged abstinence, situations or stimulipreviously associated with alcohol consumption may activate the rewardmemory, thereby also inducing craving. Craving, in turn, may result inrelapse to drinking. Stress, which on a chemical level is mediated by theneurotransmitter serotonin, can enhance neuroadaptation as well astrigger the reward memory.

Chronic alcohol use

Sensitization(i.e., neuroadaptation)

Prolonged abstinence

Reward memory

Stress(mediated by

serotonin)

Craving

Relapse

Initial abstinence

Withdrawal

Changes in neurotrans-mitters (e.g., opiates,dopamine, glutamate,

and GABA)

of the characteristics of AOD cravingwith specific neural systems (see figure2 below). Although this model is basedon both clinical experience and labora-tory data, it should be considered spec-ulative until further confirmation hasbeen obtained. Nevertheless, the modelcan allow researchers to test conceptsand hypotheses and to link subjectiveexperiences such as craving to physicalbrain structures.

Alcohol (like all other drugs of abuse)activates a brain area called the nucleusaccumbens, which is thought to be the

brain’s “reward center.” Neurons locatedin the nucleus accumbens extend toboth the amygdala and the frontal cortexareas. The amygdala, which is highlyconnected to brain regions that controlemotions (i.e., the limbic system), playsa role in the modulation of stress andmood. The frontal cortex areas integrateincoming sensory information, such assights, smells, and sounds. One of thoseareas is the dorsal lateral prefrontal cor-tex (DLPC), where the memories forthe rewarding aspects of AOD use andtheir salience may be located (Kalivas et

al. 1998). Accordingly, situations thatare coupled with alcohol use could be“remembered” with increased salience,because the DLPC is activated both bythe sensory information associated withthese situations and by the informationcoming from those parts of the brainthat control emotion and reward (i.e.,the amygdala and the nucleus accum-bens). Because the DLPC also sendsinformation back to the nucleusaccumbens, researchers have hypothesizedthat in recovering alcoholics, sensoryinformation associated with alcohol-

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Nucleus accumbens

F r o n t al C

o r t ex

DLPC

Inhibition

of impulse

Reward memory

Rei

nfor

cem

ent

Affe

ct

Str

ess

Obsessive-

compulsive

behaviors

Sensitization

Basal ganglia

Amygdala

Orbitofrontal cortex

Figure 2 Brain regions involved in craving. Alcohol activates the nucleus accumbens, the brain’s “reward center.” Nerve cells (i.e.,neurons) in the nucleus accumbens send information to the amygdala, which plays a role in the modulation of stress andemotions; the frontal cortex (shaded area), including the dorsal lateral prefrontal cortex (DLPC), where the reward mem-ory is thought to be located; and the basal ganglia, which plays a role in repetitive thought and behavior patterns.Neurons located in the amygdala also send information to the DLPC and the basal ganglia. The DLPC sends informationback to the basal ganglia (a connection that may play a role in obsessive-compulsive behaviors) and to the nucleusaccumbens. Feedback from the DLPC to the nucleus accumbens may sensitize the latter to further alcohol exposure.The DLPC itself is controlled by the orbitofrontal cortex, which induces impulse control.

paired situations stimulates the DLPC,which, in turn, stimulates the nucleusaccumbens and induces greater neuralactivity in that brain region (Kalivas et.al. 1998).

The activities of the DLPC and otherareas in the frontal cortex likely are con-trolled by the orbitofrontal cortex, anarea of “executive function” that lies infront of the DLPC and which is involvedin judgment (i.e., the evaluation of riskand reward). If the orbitofrontal cortexis impaired for any reason (e.g., throughgenetic predisposition, life experience,or injury), it may no longer inhibitDLPC activity to the same extent,leading to impulsive and uncontrolledactivity and behavior. Thus, impairedorbitofrontal control of the DLPC hasbeen implicated in the development ofsome obsessive-compulsive states (Saxenaet al. 1998). These states probably areassociated with the connection betweenthe DLPC and another brain regioncalled the basal ganglia, which plays arole in repetitive or stereotypic thoughtand behavior patterns.

Certain similarities exist betweenobsessive-compulsive disorder (OCD)and some aspects of craving (Modell et al. 1992a,b; Anton et al. 1996). Forinstance, alcoholics may experience re-current and irresistible thoughts (a hall-mark of OCD) about alcohol duringearly recovery and in various situations(e.g., when stimulated or under stress)during later recovery. It therefore ispossible that the basal ganglia, whenstimulated by input from the amygdalaor DLPC, may amplify or maintain thecraving phenomenon. Furthermore, ifa person drinks to relieve stress or affec-tive states such as depression or anxi-ety—both of which activate the amyg-dala—this association between alcoholconsumption and stress relief also couldbe encoded in memory through theamygdala’s connections with the DLPCand the basal ganglia. As a result, stressreduction through alcohol use wouldbecome associated with a stronger mem-ory trace, and this reinforcement couldsupport the addiction cycle. Subsequentstressful situations during recovery,regardless of their origin, would againactivate the amygdala, which, in turn,would stimulate the DLPC and the

basal ganglia, resulting in the experienceof craving for alcohol.

The neuroanatomical model suggeststhat craving is not a phenomenon thatcan be defined by a single mechanism.Instead, craving in different peoplelikely originates from different memoriesand is triggered and acted on in diverseways. Furthermore, the model indicatesthat clinicians may be able to preventor reduce craving through various mech-anisms, the salience of which may varyfrom person to person. In many ways,cognitive-behavioral therapy capitalizeson this variability in craving experienceto individualize the intervention strategies.This type of therapy helps a personexplore the relationships between lifesituations and his or her craving experi-ences. For each individual patient, thetherapist explores which familiar people,places, and things can generate cravingfor alcohol. How stress and anger stim-ulate craving is also explored. Based onthose analyses, the therapist providesmethods for reducing or avoiding theserisky situations or moods.

The pharmacological managementof craving and relapse ultimately will beguided by a greater understanding ofthe neurochemical systems that play cru-cial roles in this putative neural cravingnetwork. Some early evidence suggeststhe following roles for various neurotrans-mitter systems (Koob and Roberts 1999):

• Dopamine is involved in reinforce-ment mechanisms.

• Glutamate may play a role in sensi-tization mechanisms.

• GABA may be involved in sensitiza-tion mechanisms as well as in stressand affective mechanisms.

• Serotonin has been implicated instress and affective mechanisms aswell as in impulsivity and obsessive-compulsive mechanisms.

• Endogenous opiates may play a rolein reinforcement mechanisms as wellas in stress and affective mechanisms.

The brain and its functions aremuch too complicated, however, to

allow for such simplified theories. Instead,it is likely that many of these neuro-transmitter systems—as well as othersystems not discussed here—play mul-tiple and interconnected roles in thegeneration and maintenance of craving.Because various medications affectthese neurochemical systems in differ-ent ways, combinations of medicationsmay more effectively reduce cravingthan any single medication alone.

Measurement of Craving

As the neuroanatomical model of crav-ing indicates, numerous stimuli actingthrough a variety of mechanisms mayinduce craving. This diversity of stim-uli and mechanisms results in highlyvariable craving experiences in differentpeople. As a result, measurement ofcraving is complicated. Nevertheless,craving assessment is important,because craving appears to be a practi-cally useful concept that may help clin-icians and researchers gauge treatmentsuccess and predict relapse. Improvedmeasurement of craving therefore maylead to more accurate relapse predictionsand, subsequently, to more effectiveclinical care. Accordingly, it is crucialthat clinicians and researchers under-stand, define, and measure cravingmore thoroughly. Furthermore, the term“craving” is used routinely in treatmentsettings and commercial advertising,and people who abuse or are dependenton AODs appear to understand that alink exists between addiction and craving.Accordingly, the accurate measurementof craving might help patients get abetter understanding of the severity oftheir addiction.

Until recently, craving most com-monly was measured using single-itemanalog scales—that is, the drinker wasasked to rate (e.g., on a scale of 1 to10) in a rather subjective and globalfashion, his or her level of “craving,”“urge to drink,” or “desire to drink.” In general, however, single-item analogscales cannot measure craving (or anyother variable) as precisely as multi-item questionnaires. Therefore, severalmulti-item scales recently have beendeveloped to assess certain specific


aspects of the craving phenomenon.These scales include the Alcohol UrgeQuestionnaire (AUQ) (Bohn et al. 1995),the Obsessive Compulsive DrinkingScale (OCDS) (Anton et al. 1995, 1996),the Alcohol Craving Questionnaire-Now (ACQ-Now) (Singleton et al.1995), and the Penn Alcohol CravingScale (Flannery et al. 1999).

Because craving is a multidimensional,temporary, and ephemeral phenomenon,different instruments may be most appro-priate for assessing specific aspects ofcraving (Miller et al. 1996). For example,the AUQ may be most useful for measur-ing very recent levels of craving, whereasthe OCDS may be better suited fordetermining the amount of cravingexperienced over a 1-week interval.

Scientists also are developing proce-dures to simulate and stimulate cravingin clinical and laboratory settings. Cravingstudies in laboratory settings are partic-ularly important for studies that aim tobetter define the craving phenomenon.For example, brain-imaging studies can only be performed in a laboratorybecause—at least for the foreseeablefuture—it is not possible to obtainimages of people’s brain activities whilethey are following their daily routines.Therefore, such analyses require reliablemethods for inducing craving in sub-jects in a laboratory setting.

In contrast to brain-imaging studies,researchers have attempted to obtainminute-to-minute recordings of behav-ioral and physiological variables associ-ated with craving in both clinical andnatural settings (i.e., during normaldaily routine). These techniques requirestudy participants to record their levelof craving regularly in a hand held datadevice and to note what they were doingor thinking at the time they experiencedcraving. If such monitoring techniquescould be refined further, they couldprove useful for evaluating the effec-tiveness of intervention techniquesdesigned to reduce craving.

Clinical Implications of Evaluating Craving

Based on the neuroanatomical modelof craving, various psychiatric illnesses

are likely to affect a person’s experienceor expression of craving. For example,in people with depression, orbitofrontalcortical function is thought to be sup-pressed. Consequently, in alcoholicswho suffer from depression, theorbitofrontal cortex’s inhibitory effect(e.g., cognitive restraints) on drinkingimpulse might be impaired, leading togreater craving. Similarly, anxiety isthought to be mediated by the limbicsystem, which is connected to the

amygdala. Accordingly, alcoholics whosuffer from anxiety might be morestrongly stimulated to drink as a resultof increased activity of the amygdalaand limbic system. To reduce cravingand improve outcome (i.e., decreaserisk of relapse), treatment of depressedor anxious alcoholics therefore shouldaddress both the psychiatric disorderand the craving for alcohol, becauseboth phenomena appear to be inter-twined. Similar considerations probablyapply to various other coexisting psy-chiatric conditions that involve moodand anxiety disturbances, such as panicdisorder, post-traumatic stress disorder,obsessive-compulsive illness, bipolardisorder, and social phobia.

People who are born with defects inorbitofrontal-lobe functioning or inwhom the maturation of orbitofrontal-lobe functioning during developmentis delayed could be excessively prone to developing alcohol dependence.Orbitofrontal-lobe function deficitscould lead to a lack of impulse control,which, in turn, could exacerbate theexpression of craving, because the per-son would be likely to “give in” to all

desires and urges. The fact that childrenwith conduct disorder are at elevatedrisk for developing early onset alco-holism provides some support for thisnotion. A similar scenario could occurin the late stages of alcoholism, whenthe years of alcohol abuse have resultedin frontal lobe damage and whenimpulsive and compulsive alcohol usecontinue despite dire medical, social,and legal consequences. This type ofbrain dysfunction leads to the relativelypoor prognosis with respect to treat-ment effectiveness for these people. In fact, the main hope for achievingrecovery for people who have reachedthis advanced stage of alcoholism iscomplete environmental control ofaccess to alcoholic beverages for pro-tracted periods of time.

The evaluation of craving duringclinical treatment also can help clini-cians manage their clients’ treatment inseveral ways. First, “craving” is a usefulconcept for bridging our understandingof addiction and what we know aboutactual drinking behavior—that is, crav-ing influences drinking behavior and isa central feature of addiction. A discus-sion of the patient’s craving thereforecan facilitate therapeutic discussionsbetween treatment provider and client.

Second, the results of repeated eval-uation and monitoring of craving mayinfluence treatment decisions. Forexample, treatment approaches thatinclude craving management may beappropriate for patients reporting aconsiderable amount of urges for—orthoughts of—drinking, particularly forpatients who have difficulty resistingsuch urges. Such treatment approachesinclude cognitive-behavioral therapy oranticraving medications (e.g., naltrexone).For clients who continue to experiencepersistent craving despite receivingsome craving management therapy,alternative treatment approaches ormore intensive care should be considered.For example, clients taking naltrexonewho still experience some degree ofcraving—either during or immediatelyafter treatment—may require extendedtherapy. Alternatively, once additionalanticraving medications (e.g., acam-prosate) become available, combinationtherapy with several medications may

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Various psychiatric illnesses

are likely to affect a person’sexperience or

expression of craving.


be appropriate for some patients whoexperience severe craving.

Third, clinicians can teach clients tomonitor themselves for the presence ofvarious craving phenomena and therebyassist in their own long-term care. Forthose patients, the recognition of crav-ing could serve as an early warning signof relapse that can prompt the use ofpreventive measures before drinkingactually occurs.

In clinical practice, the assessmentof craving can be difficult, however,because some clients may deny experi-encing it. For those patients, the clini-cian should inquire about urges,desires, and, most importantly, thoughtsof drinking, because many clients expresscraving only by reporting thoughts orimages of drinking situations.2 Finally,when making treatment decisions,treatment providers must consider thepresence of psychiatric conditions thatmay influence craving.

New Horizons andUnresolved Questions

New technological tools have openedup new roads for enhancing under-standing of the mechanisms underlyingcraving and AOD dependence. Forexample, the development of animalmodels, coupled with a focus on ana-lyzing cellular networks in the brain

(Pierce et al. 1998), should help iden-tify and fit together increasingly smallpieces of the puzzle. Analyses that inte-grate neurochemistry, neuroanatomyand, perhaps, genetic vulnerability alsohave enormous potential to advancecurrent understanding of craving.Furthermore, application of the latestbrain-imaging techniques in humanswill begin the process of translatingresults obtained in basic science labora-tories to clinical settings (George et al. 1999). Such analyses already havebegun to unravel the neuroanatomicbasis of craving in cocaine addicts (Grantet al. 1996). In alcoholics, such studiesare only just beginning; however, theresults could take researchers and clini-cians to the next level of investigationand understanding.

The treatment of alcoholism withanticraving medications also is receiv-ing increasing attention and is beingactively studied. A better understandingof the neurochemical basis of craving,combined with the development ofimproved techniques to measure craving,should allow researchers to design andtest more precisely targeted medicationsin clinical populations.

The relationship between the expres-sion of craving and relapse also must beinvestigated in more detail. For exam-ple, researchers still must determine theextent to which drinking behavior influ-ences craving, or vice versa. Additional

studies need to assess the relative influ-ences of environmental factors andinternal variables on the expression andmaintenance of craving. The results ofsuch analyses could help in the designof targeted medications or of therapiescombining psychosocial and biomedicalapproaches.

Finally, it is important to developimproved methods for reliably measur-ing craving as well as new and validapproaches for inducing craving inclinical laboratory settings. Only whensuch tools are available can researchersaddress some of the issues mentionedin this article.

To accomplish these goals, consider-able multidisciplinary communicationand cooperation between basic andclinical scientists are needed, as is sup-port for craving-related research fromfunding organizations. Over the pastfew years, the concept of craving, whichhad been virtually ignored for more than30 years, has experienced a resurgencein interest, research, and discussion. Asa result, understanding of the cravingphenomenon has increased rapidlyand, one hopes, will continue to do so.This progress, in turn, should translate


G L O S S A R YAffect: An outward manifestation of a person’s feelings

or emotions.Classical conditioning: A concept first developed by

the Russian scientist Pavlov positing that when a neutral stimulus (e.g., the sound of a bell) is repeatedly paired with a nonconditioned stimulus (e.g., food) which induces a certain reaction (e.g., salivation), the neutral stimulus eventually becomes a conditioned stimulus that elicits the same reaction as the nonconditioned stimulus with which it was initially paired.

Homeostasis: The maintenance of a constant internal environment of the body, achieved through the body’sregulation of body temperature, blood pressure, heart rate, respiration, levels of minerals in the blood, and so forth.

Neuroadaptation: Changes in the function of certain braincells that occur in response to long-term changes in thebody’s internal and external environment (e.g., prolongedpresence of alcohol in the brain).

Neurotransmitters: Chemicals that allow communicationamong nerve cells and between nerve cells and other cells inthe body; neurotransmitters include, among others,dopamine, serotonin, gamma-aminobutyric acid (GABA),and endogenous opioids.

Tolerance: The need of a chronic drinker to consume increas-ing amounts of alcohol over time in order to achieve thesame effect (e.g., euphoria) that the drinker initially experi-enced from smaller quantities.

Withdrawal: The physiological (e.g., tremors) and psychologi-cal (e.g., anxiety) effects that occur if a chronic drinker sud-denly abstains from alcohol use.

2Often, such thoughts or images of drinking situa-tions occur only at certain times (i.e., are temporallycued). For example, in employed alcoholics suchthoughts may occur at the end of the workday,when they used to go to a bar after leaving work.

into improved understanding andtreatment of alcohol dependence. ■

Acknowledgment

Mary Radin assisted in the preparationof this manuscript.

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Will Hoffman

Will Hoffman

craving models and implications for treatment_anton

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