Drug and Alcohol Depenoknce,
Elsevier Scientific Publishers
127
30 (1992) 127 - 131 Ireland Ltd.
Craving: consensus of status and agenda for future research* Roy W. Pickensa and Chris-Ellyn aAddiction Research
Center National
Institute
on Drug Abuse Baltimore,
Health Sciaees,
Johansonb
MD and bUnifomed
Services University of the
Bethesda, MD (U.S.A.)
(Accepted December 9th, 1991)
The term craving is used frequently in relationship to drug abuse and its treatment but there is disagreement over its definition and role. In February 1991, a meeting of experts from several disciplines, sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse, was convened with the goal of reaching consensus about the importance of craving and to suggest a future research program. The participants agreed that craving is a subjective state in humans that is associated with drug dependence but little is known about its determinants, relationship to drug taking, and measurement. To advance our knowledge, a substantial research program is required. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse. Key words: craving; determinants
of drug abuse; determinants
Introduction The term ‘craving’ is being used by the lay public as well as scientists with increasing frequency in relationship to drug abuse and its treatment. Despite this, it is generally agreed that our knowledge about craving is limited. Further, the term is often used differently by different investigators and there appears to be disagreement among experts from different disciplines over its definition and usefulness. *The opinions expressed in this paper are those of the authors and do not necessarily represent the views of the National Institute on Drug Abuse, Department of Health and Human Services, Uniformed Services University of the Health Sciences, or the Department of Defence of the United States Government. Correspondence to: R.W. Pickens, Addiction Research Center, National Institute on Drug Abuse, P.O. Box 5180, Baltimore, MD 21224, U.S.A. Printed and Published in Ireland
of relapse; research agenda
These differences range from the extremes of those who believe craving is the major determinant of drug-taking behavior, to those who lieve that craving is an epiphenomenon or hypothetical construct that should be ignored in scientific investigations. There is also no standardized methodology for measuring craving or even a general agreement about how to develop psychometrically sound indices. Despite these differences or perhaps because of them, there are compelling theoretical and practical reasons for attempting to reach some consensus on the status of craving. To address the issue, a meeting on craving in drug abuse research and treatment sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse was held on February 27-28, 1991. The goal of the meeting was to bring together a wide range of experts in the drug abuse research field to discuss the utility of
128
the concept*. Experts ranged from scientists involved in basic animal studies to those conducting clinical treatment research. There was a concerted effort to invite participants with divergent views. Although formal presentations were given by each of the participants, the meeting was designed to maximize discussion of different perspectives. Theoretically, a successful research effort designed to understand the nature and determinants of craving might result in an increase in our understanding of drug abuse in humans and enable clinical researchers to incorporate newly gained knowledge concerning the role of craving into treatment interventions. At a time when increasing importance is being placed on the need to improve drug abuse treatment, an increased understanding of craving might have tremendous impact in this regard. On the other hand, if craving could not survive a rigorous scientific scrutiny, the effort might be useless and could divert researchers from more productive approaches. Practically, the popularity of the idea of craving and the frequency of the use of the term in relationship to explaining relapse to drug abuse has encouraged scientists involved in the development of medications for the treatment of drug abuse to target some of their resources to produce a medication to treat craving. Unless *The following (San Francisco
experts were present: Neal Benowitz, General Medical Center); Anna
M.D. Rose
Childress, Ph.D. (Philadelphia VA Medical Center); Ned L. Cooney, Ph.D. (Yale University); Marian Fischman, Ph.D. (Johns Hopkins University School of Medicine); Jack E. Henningfield, Ph.D. (National Institute on Drug Abuse); John R. Hughes, M.D. (University of Vermont); Chris-Ellyn Johanson, Ph.D. (Uniformed Services University of the Health Sciences); Thomas R. Kosten, M.D. (Yale University); Lynn T. Kozlowski, Ph.D. (The Pennsylvania State University); Arnold M. Ludwig, M.D. (University of Kentucky); Richard Millstein, J.D. (National Institute on Drug Abuse); David Newlin, Ph.D. (National Institute on Drug Abuse); Roy W. Pickens, Ph.D. (National Institute on Drug Abuse); Robert M. Post, M.D. (National Institute of Mental Health); Charles R. Schuster, Ph.D. (National Institute on Drug Abuse); Shepard Siegel, Ph.D. (McMaster University); Steven T. Tiffany, Ph.D. (Purdue University); Roy A. Wise, Ph.D. (Concordia University); James H. Woods, Ph.D. (University of Michigan).
there is some agreement concerning the role of craving in relapse and how to measure it, it is possible that these limited resources would be unwisely allocated. Thus, it seemed important and timely to convene a group of experts to attempt to reach some level of consensus about the importance of craving and to suggest research that might be helpful in resolving some of the disagreements among researchers with different perspectives. This paper briefly describes the outcome of this meeting. General
Consensus
It was generally agreed that craving is a subjective state in humans that is associated with drug dependence. Many researchers contend that craving is a significant factor in continued drug use, as well as in relapse to drug abuse after treatment, and thus deserves intensive study, particularly since such study might contribute to the development of clinical methods for treating drug abuse and preventing relapse. Drug abusers also may attribute their continued drug use or relapse to craving. However, because of its subjective nature, the study of craving poses formidable problems to experimental researchers. The global and imprecise definition of craving results in misunderstandings and misinterpretations on the part of both subjects and patients as well as experimenters, a danger that is always posed when a common lay term is incorporated into scientific parlance. One consequence of imprecise definitions, as the presentations of experimental results at the conference revealed, is that craving has been measured in a variety of ways. The majority of measurements involve self-report questionnaires which range in complexity from endorsements of simple yes-no statements (‘I crave drug x’) to questionnaires that have attempted to analyze multiple aspects of craving (e.g. Shiffman and Jarvik, 1976; Tiffany, 1990). In the case of the former, simple statements have used a variety of terms (e.g. urges, desires, wanting) and metrics (analog scales, Likert scales, true-false questions). In addition to measuring craving by verbal report, many
129
investigators advocate the measurement of physiological changes as indices of craving (Tiffany, 1990). While the objectivity of such measurements is appealing, their relationship to craving and drug-taking is only beginning to be explored. Finally, many investigators view actual drug-taking as the only valid measure of craving, rather than the consequence of craving. This is particularly the case in animal studies. Although verbal and physiological measures, and drug-taking are often highly correlated, in some studies, both laboratory-based and clinically-based, investigators have found substantial divergences between verbal reports of the subjective state of craving, physiological changes, and occurrence of actual drug-taking. For instance, Fischman et al. (1990) reported that when treated with desipramine, an antidepressant that has been proposed as a treatment for cocaine abuse, cocaine abusers participating in a laboratory experiment did not decrease their choice of self-administering cocaine. However, at the same time, they reported decreases in craving as defined by the verbal report of ‘I want cocaine’. Conversely, administration of nicotine gum to cigarette smokers decreased several measures of tobacco intake while leaving self-reported desire to smoke unaffected (Nemeth-Coslett and Henningfield, 1986). Similarly, in a clinical study evaluating the ability of desipramine to decrease cocaine abuse, cocaine use significantly decreased within two weeks whereas decreases in craving only occurred several weeks later (Gawin et al., 1989). These divergences between verbal reports and drug-taking have led to the general conclusion that craving is neither a sufficient nor necessary determinant of drug-taking. Given the enormous complexity of the drug abuse situation in the United States, it would have been extremely unlikely that a single factor, the experience of craving, could account for continued drug abuse and relapse. However, most participants still believed that craving plays some role. The experience of craving is likely a dynamic state, the reporting of which is influenced by environmental factors. In clinical
terms, a variety of circumstances can modulate experiences or expressions of craving. Using behavioral analytic terms, this translates into the view that craving has multiple determinants. Regardless of how this conclusion is phrased, however, the presentations at the meeting revealed that only a narrow range of variables has been systematically investigated and there is considerable disagreement about what factors or determinants are most important for craving. There is also disagreement about whether the nature of craving is substance-specific, whether the determinants are the same across drugs, or whether both negative and positive moods influence craving. Finally, there are even some who contend that the term craving is too general and that it should be dissected into more refined terms such as urges and desires. Despite these different viewpoints and the general consensus that little is known about the causes of craving, there was general agreement that two likely causes of craving are acute drug deprivation and presentation of drug-related stimuli. It was also agreed that to some extent these influences develop through associations between certain features of the internal and external environment and drug-taking (or drug availability) as well as drug withdrawal. These associations or learning processes have been studied with some degree of success in both experimental laboratories and clinical situations using not only human subjects but non-humans as well. But a complete delineation of the conditions that modify the experience or expression of craving for specific drugs is lacking. Furthermore as discussed above, methods for measuring verbal reports have been generally deficient and the development of reliable and valid physiological measures is still in its infancy. For non-human studies, there are reliable objective measures (e.g. drug-maintained responding), but their validity as indicators of human craving is not clear. Research
impediments
One of the major conclusions that can be drawn from the consensus statement described
130
above is that an adequate assessment of the role of craving in drug abuse has been hampered by methodological problems. Most of these problems are self-evident but the failure of researchers to fully consider them indicates a need for describing some of the most important ones. One of the implications following from the multidetermined nature of craving is that the conditions that prevail within laboratory settings can greatly influence outcome. However, there is little general consensus concerning what variables to hold constant, what to vary (i.e. what factors are most likely to yield variations in outcome), and even when to measure. Most participants agreed that craving is not a continuous state so it is not obvious when to measure it and how to determine the temporal relationship between independent variables and the experiencing of craving. One variable that needs to be considered is the relationship of the experimental subject to treatment or the ‘demand’ characteristics of the experimental situation. For instance, if the subjects are also patients that are being maintained on methadone, they might increase their reports of craving in order to obtain higher doses of the medication. Patients in drug-free programs may have the opposite tendency because they believe that their treatment providers are expecting them to show improvement, i.e. not experience craving. Perceived vs. real drug availability is also likely to be a major factor in craving. However, in protocols involving treatment patients, it may be unethical to try to manipulate this variable. If subjects are active drug abusers in a protocol unrelated to treatment, they might easily believe that the amount of drug that they will obtain in the experiment is related to the intensity of their craving report. In studies interested in determining what environmental influences currently elicit craving, the idiosyncratic nature of the development of associations may require individualized protocols, which are difficult to compare in a scientifically rigorous manner. Different populations of subjects may also differ in the vernacular of their language so that measuring instruments requiring verbal responses will have to be broad
enough to take these differences into account. For this reason and others, some investigators have suggested that subjects be trained or instructed in the appropriate terminology, although these investigators also realize that the training itself can bias outcome. Finally, since most drug abusers today are polydrug abusers, it is not clear whether craving for one drug can be studied in isolation. For instance, if investigators are interested in the determinants of cocaine craving, how does the now-common experimental requirement of abstention from smoking in the laboratory influence cocaine craving? In summary, in any new research effort such as that proposed below, careful attention must be paid to methodological issues that have been largely ignored. While we have delineated some of the most obvious of these, there are undoubtedly many others and researchers will have to be continually refining their methods to improve the scientific rigor in an area, i.e. measurement of subjective states, where pitfalls and uncontrolled influences abound. Future research It should be obvious that a substantial new research effort is required to elucidate the determinants of craving in a scientifically acceptable way and to compare these determinants to those that influence continued drug abuse and relapse. It is our contention that the importance of craving for understanding continued drug use and relapse will be directly related to the extent that these two sets of determinants (of craving and of drug-taking) overlap.* To mount this research effort, a broad spectrum of studies are indicated. Most notably, reliable and valid self-report measures need to be developed. Psychophysiological studies conducted under a variety of pharmacological, behavioral and environmental conditions are
*The authors are restricting their assessment of the importance of craving to its implication for continued drug use and relapse. As with many subjective phenomena, there are undoubtedly other reasons for studying craving that are beyond the scope of this consensus statement.
131
particularly needed as their development may help obviate the problems of using self-report measures. At the same time, or rather concurrently, a better understanding of the biological bases of craving is needed. For instance, brain imaging studies may be useful in identifying brain areas mediating craving. Non-human studies aimed at identifying specific neurochemical events associated with craving may also indicate CNS mechanisms. Molecular studies are needed to identify the genetic mechanism that transduces experiences into behavior and subjective states, and/or that function as ‘memory’ to transduce acute experiences into long-term consequences such as craving. Finally, studies are needed to develop effective methods for eliminating craving to be used as adjuncts for improving the effectiveness of treatment strategies. It is clear that the necessary research program for determining the importance of craving in continued drug use and relapse is massive. To maximize its probability of success, careful and coordinated planning is required, particularly at this time of restrictive scientific funding. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse. However, despite the general optimism of the participants in the meeting, until more substantial progress is achieved, the question will remain of whether the concept of craving adds
little more than a convenient word for expressing the probability of an individual engaging in drug-taking behavior. In that case, the latter can still best be understood using the approach of elucidating the environmental conditions and underlying brain mechanisms that control drug self-administration. Acknowledgement
The preparation of this manuscript by CEJ was supported by grants from the National Institute on Drug Abuse, DA06030 and DA06175. References Fischman, M.W., Foltin, R.W., Nestadt, G. and Pearlson, G.D. (1990) Effects of desipramine maintenance on cocaine self-administration by humans. J. Pharmacol. Exp. Ther. 253, 760-770. Gawin, F.H., Kleber, H.D., Byck, R., Rounsaville, B.J., Kosten, T.R., Jatlow, PI. and Morgan, C. (1989) Desipramine facilitation of initial cocaine abstinence. Arch. Gen. Psychiat. 46, 117-121. Nemeth-Coslett, R. and Henningfield, J.E. (1986) Effects of nicotine chewing gum on cigarette smoking and subjective and physiologic effects. Clin. Pharmacol. Ther. 39, 625-630. Shiffman, S.M. and Jarvik, M.E. (1976). Smoking withdrawal symptoms in two weeks of abstinence. Psychopharmacology 50, 35 - 33. Tiffany, S.T. (1990). A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. Psychol. Rev. 97, 147 - 168.
Elsevier Scientific Publishers
127
30 (1992) 127 - 131 Ireland Ltd.
Craving: consensus of status and agenda for future research* Roy W. Pickensa and Chris-Ellyn aAddiction Research
Center National
Institute
on Drug Abuse Baltimore,
Health Sciaees,
Johansonb
MD and bUnifomed
Services University of the
Bethesda, MD (U.S.A.)
(Accepted December 9th, 1991)
The term craving is used frequently in relationship to drug abuse and its treatment but there is disagreement over its definition and role. In February 1991, a meeting of experts from several disciplines, sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse, was convened with the goal of reaching consensus about the importance of craving and to suggest a future research program. The participants agreed that craving is a subjective state in humans that is associated with drug dependence but little is known about its determinants, relationship to drug taking, and measurement. To advance our knowledge, a substantial research program is required. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse. Key words: craving; determinants
of drug abuse; determinants
Introduction The term ‘craving’ is being used by the lay public as well as scientists with increasing frequency in relationship to drug abuse and its treatment. Despite this, it is generally agreed that our knowledge about craving is limited. Further, the term is often used differently by different investigators and there appears to be disagreement among experts from different disciplines over its definition and usefulness. *The opinions expressed in this paper are those of the authors and do not necessarily represent the views of the National Institute on Drug Abuse, Department of Health and Human Services, Uniformed Services University of the Health Sciences, or the Department of Defence of the United States Government. Correspondence to: R.W. Pickens, Addiction Research Center, National Institute on Drug Abuse, P.O. Box 5180, Baltimore, MD 21224, U.S.A. Printed and Published in Ireland
of relapse; research agenda
These differences range from the extremes of those who believe craving is the major determinant of drug-taking behavior, to those who lieve that craving is an epiphenomenon or hypothetical construct that should be ignored in scientific investigations. There is also no standardized methodology for measuring craving or even a general agreement about how to develop psychometrically sound indices. Despite these differences or perhaps because of them, there are compelling theoretical and practical reasons for attempting to reach some consensus on the status of craving. To address the issue, a meeting on craving in drug abuse research and treatment sponsored by the Addiction Research Center (ARC) of the National Institute on Drug Abuse was held on February 27-28, 1991. The goal of the meeting was to bring together a wide range of experts in the drug abuse research field to discuss the utility of
128
the concept*. Experts ranged from scientists involved in basic animal studies to those conducting clinical treatment research. There was a concerted effort to invite participants with divergent views. Although formal presentations were given by each of the participants, the meeting was designed to maximize discussion of different perspectives. Theoretically, a successful research effort designed to understand the nature and determinants of craving might result in an increase in our understanding of drug abuse in humans and enable clinical researchers to incorporate newly gained knowledge concerning the role of craving into treatment interventions. At a time when increasing importance is being placed on the need to improve drug abuse treatment, an increased understanding of craving might have tremendous impact in this regard. On the other hand, if craving could not survive a rigorous scientific scrutiny, the effort might be useless and could divert researchers from more productive approaches. Practically, the popularity of the idea of craving and the frequency of the use of the term in relationship to explaining relapse to drug abuse has encouraged scientists involved in the development of medications for the treatment of drug abuse to target some of their resources to produce a medication to treat craving. Unless *The following (San Francisco
experts were present: Neal Benowitz, General Medical Center); Anna
M.D. Rose
Childress, Ph.D. (Philadelphia VA Medical Center); Ned L. Cooney, Ph.D. (Yale University); Marian Fischman, Ph.D. (Johns Hopkins University School of Medicine); Jack E. Henningfield, Ph.D. (National Institute on Drug Abuse); John R. Hughes, M.D. (University of Vermont); Chris-Ellyn Johanson, Ph.D. (Uniformed Services University of the Health Sciences); Thomas R. Kosten, M.D. (Yale University); Lynn T. Kozlowski, Ph.D. (The Pennsylvania State University); Arnold M. Ludwig, M.D. (University of Kentucky); Richard Millstein, J.D. (National Institute on Drug Abuse); David Newlin, Ph.D. (National Institute on Drug Abuse); Roy W. Pickens, Ph.D. (National Institute on Drug Abuse); Robert M. Post, M.D. (National Institute of Mental Health); Charles R. Schuster, Ph.D. (National Institute on Drug Abuse); Shepard Siegel, Ph.D. (McMaster University); Steven T. Tiffany, Ph.D. (Purdue University); Roy A. Wise, Ph.D. (Concordia University); James H. Woods, Ph.D. (University of Michigan).
there is some agreement concerning the role of craving in relapse and how to measure it, it is possible that these limited resources would be unwisely allocated. Thus, it seemed important and timely to convene a group of experts to attempt to reach some level of consensus about the importance of craving and to suggest research that might be helpful in resolving some of the disagreements among researchers with different perspectives. This paper briefly describes the outcome of this meeting. General
Consensus
It was generally agreed that craving is a subjective state in humans that is associated with drug dependence. Many researchers contend that craving is a significant factor in continued drug use, as well as in relapse to drug abuse after treatment, and thus deserves intensive study, particularly since such study might contribute to the development of clinical methods for treating drug abuse and preventing relapse. Drug abusers also may attribute their continued drug use or relapse to craving. However, because of its subjective nature, the study of craving poses formidable problems to experimental researchers. The global and imprecise definition of craving results in misunderstandings and misinterpretations on the part of both subjects and patients as well as experimenters, a danger that is always posed when a common lay term is incorporated into scientific parlance. One consequence of imprecise definitions, as the presentations of experimental results at the conference revealed, is that craving has been measured in a variety of ways. The majority of measurements involve self-report questionnaires which range in complexity from endorsements of simple yes-no statements (‘I crave drug x’) to questionnaires that have attempted to analyze multiple aspects of craving (e.g. Shiffman and Jarvik, 1976; Tiffany, 1990). In the case of the former, simple statements have used a variety of terms (e.g. urges, desires, wanting) and metrics (analog scales, Likert scales, true-false questions). In addition to measuring craving by verbal report, many
129
investigators advocate the measurement of physiological changes as indices of craving (Tiffany, 1990). While the objectivity of such measurements is appealing, their relationship to craving and drug-taking is only beginning to be explored. Finally, many investigators view actual drug-taking as the only valid measure of craving, rather than the consequence of craving. This is particularly the case in animal studies. Although verbal and physiological measures, and drug-taking are often highly correlated, in some studies, both laboratory-based and clinically-based, investigators have found substantial divergences between verbal reports of the subjective state of craving, physiological changes, and occurrence of actual drug-taking. For instance, Fischman et al. (1990) reported that when treated with desipramine, an antidepressant that has been proposed as a treatment for cocaine abuse, cocaine abusers participating in a laboratory experiment did not decrease their choice of self-administering cocaine. However, at the same time, they reported decreases in craving as defined by the verbal report of ‘I want cocaine’. Conversely, administration of nicotine gum to cigarette smokers decreased several measures of tobacco intake while leaving self-reported desire to smoke unaffected (Nemeth-Coslett and Henningfield, 1986). Similarly, in a clinical study evaluating the ability of desipramine to decrease cocaine abuse, cocaine use significantly decreased within two weeks whereas decreases in craving only occurred several weeks later (Gawin et al., 1989). These divergences between verbal reports and drug-taking have led to the general conclusion that craving is neither a sufficient nor necessary determinant of drug-taking. Given the enormous complexity of the drug abuse situation in the United States, it would have been extremely unlikely that a single factor, the experience of craving, could account for continued drug abuse and relapse. However, most participants still believed that craving plays some role. The experience of craving is likely a dynamic state, the reporting of which is influenced by environmental factors. In clinical
terms, a variety of circumstances can modulate experiences or expressions of craving. Using behavioral analytic terms, this translates into the view that craving has multiple determinants. Regardless of how this conclusion is phrased, however, the presentations at the meeting revealed that only a narrow range of variables has been systematically investigated and there is considerable disagreement about what factors or determinants are most important for craving. There is also disagreement about whether the nature of craving is substance-specific, whether the determinants are the same across drugs, or whether both negative and positive moods influence craving. Finally, there are even some who contend that the term craving is too general and that it should be dissected into more refined terms such as urges and desires. Despite these different viewpoints and the general consensus that little is known about the causes of craving, there was general agreement that two likely causes of craving are acute drug deprivation and presentation of drug-related stimuli. It was also agreed that to some extent these influences develop through associations between certain features of the internal and external environment and drug-taking (or drug availability) as well as drug withdrawal. These associations or learning processes have been studied with some degree of success in both experimental laboratories and clinical situations using not only human subjects but non-humans as well. But a complete delineation of the conditions that modify the experience or expression of craving for specific drugs is lacking. Furthermore as discussed above, methods for measuring verbal reports have been generally deficient and the development of reliable and valid physiological measures is still in its infancy. For non-human studies, there are reliable objective measures (e.g. drug-maintained responding), but their validity as indicators of human craving is not clear. Research
impediments
One of the major conclusions that can be drawn from the consensus statement described
130
above is that an adequate assessment of the role of craving in drug abuse has been hampered by methodological problems. Most of these problems are self-evident but the failure of researchers to fully consider them indicates a need for describing some of the most important ones. One of the implications following from the multidetermined nature of craving is that the conditions that prevail within laboratory settings can greatly influence outcome. However, there is little general consensus concerning what variables to hold constant, what to vary (i.e. what factors are most likely to yield variations in outcome), and even when to measure. Most participants agreed that craving is not a continuous state so it is not obvious when to measure it and how to determine the temporal relationship between independent variables and the experiencing of craving. One variable that needs to be considered is the relationship of the experimental subject to treatment or the ‘demand’ characteristics of the experimental situation. For instance, if the subjects are also patients that are being maintained on methadone, they might increase their reports of craving in order to obtain higher doses of the medication. Patients in drug-free programs may have the opposite tendency because they believe that their treatment providers are expecting them to show improvement, i.e. not experience craving. Perceived vs. real drug availability is also likely to be a major factor in craving. However, in protocols involving treatment patients, it may be unethical to try to manipulate this variable. If subjects are active drug abusers in a protocol unrelated to treatment, they might easily believe that the amount of drug that they will obtain in the experiment is related to the intensity of their craving report. In studies interested in determining what environmental influences currently elicit craving, the idiosyncratic nature of the development of associations may require individualized protocols, which are difficult to compare in a scientifically rigorous manner. Different populations of subjects may also differ in the vernacular of their language so that measuring instruments requiring verbal responses will have to be broad
enough to take these differences into account. For this reason and others, some investigators have suggested that subjects be trained or instructed in the appropriate terminology, although these investigators also realize that the training itself can bias outcome. Finally, since most drug abusers today are polydrug abusers, it is not clear whether craving for one drug can be studied in isolation. For instance, if investigators are interested in the determinants of cocaine craving, how does the now-common experimental requirement of abstention from smoking in the laboratory influence cocaine craving? In summary, in any new research effort such as that proposed below, careful attention must be paid to methodological issues that have been largely ignored. While we have delineated some of the most obvious of these, there are undoubtedly many others and researchers will have to be continually refining their methods to improve the scientific rigor in an area, i.e. measurement of subjective states, where pitfalls and uncontrolled influences abound. Future research It should be obvious that a substantial new research effort is required to elucidate the determinants of craving in a scientifically acceptable way and to compare these determinants to those that influence continued drug abuse and relapse. It is our contention that the importance of craving for understanding continued drug use and relapse will be directly related to the extent that these two sets of determinants (of craving and of drug-taking) overlap.* To mount this research effort, a broad spectrum of studies are indicated. Most notably, reliable and valid self-report measures need to be developed. Psychophysiological studies conducted under a variety of pharmacological, behavioral and environmental conditions are
*The authors are restricting their assessment of the importance of craving to its implication for continued drug use and relapse. As with many subjective phenomena, there are undoubtedly other reasons for studying craving that are beyond the scope of this consensus statement.
131
particularly needed as their development may help obviate the problems of using self-report measures. At the same time, or rather concurrently, a better understanding of the biological bases of craving is needed. For instance, brain imaging studies may be useful in identifying brain areas mediating craving. Non-human studies aimed at identifying specific neurochemical events associated with craving may also indicate CNS mechanisms. Molecular studies are needed to identify the genetic mechanism that transduces experiences into behavior and subjective states, and/or that function as ‘memory’ to transduce acute experiences into long-term consequences such as craving. Finally, studies are needed to develop effective methods for eliminating craving to be used as adjuncts for improving the effectiveness of treatment strategies. It is clear that the necessary research program for determining the importance of craving in continued drug use and relapse is massive. To maximize its probability of success, careful and coordinated planning is required, particularly at this time of restrictive scientific funding. The outcome of this research effort could have important consequences for increasing our understanding of the determinants of drug abuse. However, despite the general optimism of the participants in the meeting, until more substantial progress is achieved, the question will remain of whether the concept of craving adds
little more than a convenient word for expressing the probability of an individual engaging in drug-taking behavior. In that case, the latter can still best be understood using the approach of elucidating the environmental conditions and underlying brain mechanisms that control drug self-administration. Acknowledgement
The preparation of this manuscript by CEJ was supported by grants from the National Institute on Drug Abuse, DA06030 and DA06175. References Fischman, M.W., Foltin, R.W., Nestadt, G. and Pearlson, G.D. (1990) Effects of desipramine maintenance on cocaine self-administration by humans. J. Pharmacol. Exp. Ther. 253, 760-770. Gawin, F.H., Kleber, H.D., Byck, R., Rounsaville, B.J., Kosten, T.R., Jatlow, PI. and Morgan, C. (1989) Desipramine facilitation of initial cocaine abstinence. Arch. Gen. Psychiat. 46, 117-121. Nemeth-Coslett, R. and Henningfield, J.E. (1986) Effects of nicotine chewing gum on cigarette smoking and subjective and physiologic effects. Clin. Pharmacol. Ther. 39, 625-630. Shiffman, S.M. and Jarvik, M.E. (1976). Smoking withdrawal symptoms in two weeks of abstinence. Psychopharmacology 50, 35 - 33. Tiffany, S.T. (1990). A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. Psychol. Rev. 97, 147 - 168.
