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Cue Reactivity and Effects of Cue Exposure in Abstinent Posttreatment Drug Users
Journal of Substance Abuse Treatment, Vol. 16, No. 1, pp. 81–85, 1999 Copyright © 1998 Elsevier Science Inc. Printed in the USA. All rights reserved 0740-5472/99 $–see front matter
PII S0740-5472(98)00004-X
INTERNATIONAL PERSPECTIVE
Cue Reactivity and Effects of Cue Exposure in Abstinent Posttreatment Drug Users Ingmar H. A. Franken, msc,* Hein A. de Haan, md,† Chris W. van der Meer, md,‡ P. M. Judith Haffmans, phd,* and Vincent M. Hendriks, phd* *Research Department of Psychiatric Centre Bloemendaal, The Hague, The Netherlands †Twents Psychiatric Hospital/IVON, Enschede, The Netherlands ‡Substance Abuse Treatment Unit of Psychiatric Centre Bloemendaal, The Hague, The Netherlands
Abstract – After 12 months of inpatient treatment, 16 opiate-addicted patients were exposed to drugrelated stimuli. The results of this study indicate that cue reactivity in opiate-addicted subjects is still present after 12 months of intensive inpatient treatment. After exposing subjects to drug-related stimuli, there is an increase in craving, feelings of depression, and anger. Because posttreatment subjects are likely to be confronted with these stimuli following discharge, a reduction of this reactivity is desirable. In the present study, cue reactivity (feelings of depression, anger, tension, craving, and physical symptoms) reduced after protocolized cue exposure treatment. This effect maintained for at least 6 weeks after the last cue exposure session. © 1998 Elsevier Science Inc. Keywords – addiction; cue exposure; cue reactivity; opiate dependence; craving.
INTRODUCTION
gel, 1983). Craving, a subjective desire to use the drug of choice, is believed to play an important role in the occurrence of relapse in abstinent drug-addicted persons in their natural setting (Childress, McLellan, & O’Brien, 1986). Besides craving, other subjective cue-elicited reactions have been reported, including subjective withdrawal symptoms, subjective drug-agonistic effects, mood swings, and anxiety (Glautier & Tiffany, 1995; Powell, Gray, & Bradley, 1993). Physiological reactions that have been investigated include skin conductance, heart rate, salivation, and body temperature (Glautier, Drummond, & Remington, 1992). The exact nature of the relation between subjective and physiological signs of reactivity is still subject to debate (Tiffany, 1990). Furthermore, whether the direction of the conditioned response is drug antagonistic (withdrawal) or drug agonistic (drug-like), is still unclear (Stewart, de Wit, & Eikelboom, 1984). Conditioned reactivity to substance-related cues is believed to be an important factor within addictive use of
Cue reactivity to drug related stimuli is a frequently observed phenomenon in drug-dependent subjects (Childress et al., 1993; Powell, Gray, & Bradley, 1993). Cue reactivity refers to a classical conditioned response (CR) that occurs when a (post)addicted subject is exposed to drug-related stimuli (CS). This response is presumed to consist of physiological and/or subjective reactions (SieThis study has been conducted at the Psychiatric Centre Bloemendaal, Substance Abuse Treatment Unit. This research was supported by grants of the “Stichting tot Steun van Vereniging Bennekom” and NFGV (Nationial Fund Mental Health) grant 4325. Thanks are extended to the staff and patients of the Psychiatric Centre Bloemendaal Substance Abuse Treatment Unit for their support. In addition, we thank Irma Huijbrechts, Janet de Vries, and Ada Kwakkelstein for their help in the preparation of the manuscript. Requests for reprints should be addressed to Ingmar Franken, Psychiatric Centre Bloemendaal, Research Department, P.O. Box 53002, 2505 AA The Hague, The Netherlands. E-mail: [email protected]
Received August 15, 1997; Accepted November 5, 1997.
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alcohol (Glautier & Drummond, 1994; Staiger & White, 1991), opiates (Powell et al., 1990), nicotine (Niaura et al., 1988), and cocaine (Robbins, Ehrman, Childress, & O’Brien, 1992). These studies have shown an increase in reactivity when addicted subjects are exposed to drugrelated cues, as compared with exposure to neutral cues. Albeit, individual differences in nature and extent of the cue-elicited response cannot be ignored (Rees & Heather, 1995). Human experimental studies reveal that cue reactivity may still be present after detoxification (Powell et al., 1990). In addition, subjects who have repeatedly been exposed to drug-related cues during their treatment, showed a reduction in cue reactivity. Cue Exposure Treatment (CET) refers to a protocolized, repeated, exposure to drug-related cues, aimed at the reduction of cue reactivity by extinction, a behavior therapy technique. The present study is designed to examine the occurrence and nature of cue reactivity in subjects who have been treated for drug dependence in an intensive, drugfree inpatient treatment program for a minimal period of 12 months. At time of the study, the subjects participated in an outpatient resocialization program. It was hypothesized that cue reactivity, if present, would decrease in this population after a protocolized nine-session CET. Enduring effects of CET were studied by evaluating cue reactivity of the study subjects 6 weeks after the last exposure session.
Subjects The study group consisted of 16 patients who, after clinical detoxification and intensive inpatient treatment for at least 12 months in the drug-free therapeutic community “Emiliehoeve,” participated in the outpatient resocialization phase of the program. All subjects participated voluntarily and signed an informed consent. The inclusion criteria were: age 18–60, opiate dependency according DSM-IV criteria, inhalation (“chasing the dragon”) as primary mode of heroin administration, successful completion of the clinical treatment program, abstinence from any drugs for at least 6 months preceding the study, and adequate understanding of the Dutch language. The 16 persons in the study consisted of 7 female and 9 male subjects. The average number of clinical admissions for the treatment of drug-dependence was two (range 1–8). The mean age of these subjects was 29.5 years (range 20–42). The mean Addiction Severity Index (ASI; McLellan, Luborski, Woody, & O’Brien, 1980) score at intake was 3.3 (SD 5 1.3). The mean severity scores, ranging from no problems (0) to extreme problems (9), on the separate ASI areas were: medical problems 1.6 (SD 5 2.2), employment problems 2.9 (SD 5 2.1), alcohol problems 1.4 (SD 5 2.3), drug problems 5.5 (SD 5 1.0), legal problems 3.9 (SD 5 2.3), social problems 3.3 (SD 5 2.3), and psychiatric problems 4.3 (SD 5 1.7).
I.H.A. Franken et al.
Procedure and Assessments At intake, before detoxification, the ASI (McLellan et al., 1980) was administered to asses the severity of drugrelated problems. After detoxification, all subjects received intensive inpatient treatment for at least 12 months. In the subsequent outpatient resocialization phase of the treatment program, subjects were asked to participate in the CET program. CET consisted of a ninesession, protocolized exposure to drug-related cues. Twelve different stimuli (slides, video, drug-use material, simulation of drug-use ritual) were presented to the subjects during the study. The assessment sessions consisted of the presentation of four different cues (two slides and two videos). Every cue was presented for 5 minutes. The neutral cues consisted of a slide of a landscape and a film of natural scenery (video). The drug cues consisted of a slide of drug users who prepared smokeable heroin and inhaled heroin (“chasing the dragon”) and a film of this ritual (video). The slide and video stimuli were presented to the subjects within the same session. Assessments of reactivity to drug-related and neutral cues were conducted prior to the CET after nine CET sessions (posttreatment), and after 6 weeks following the last CET session (follow-up). These assessments consisted of a (single-item) craving scale, the Profile of Mood States (POMS) and the Physical Symptom Checklist (PSC). The CET and assessment procedure have been described by Powell, Gray, and Bradley (1993). Craving Scale. A single-item self-rating scale was used to assess the intensity of craving each minute during the presentation of the stimuli. The scale ranged from 0 (no craving) to 10 (excessive craving). For each stimulus a mean craving score of the subject was calculated. For purposes of the study, craving was defined as the strength of the attraction to use drugs (Powell,1995). It was explicitly communicated with the subjects that craving could also occur when they felt they were able to resist drug use. Profile of Mood States. The abridged Dutch version of the POMS (McNair, Lorr, & Droppelman, 1971) has acceptable psychometric properties. Five subscales were used in this study (Depression, Anger, Fatigue, Vigor, and Tension). Furthermore, a total score is calculated by adding the scores of the subscales used (the subscale Vigor is recoded). The POMS consisted of 32 items that can be scored on a 5-point scale, from 0 (none) to 5 (extremely intense). Physical Symptoms Checklist. This checklist was adopted from Powell, Bradley, and Gray (1992). The PSC measures physical symptoms that reflect characteristics of opiate withdrawal and drug-agonistic states. Furthermore, a residual category was used to report ambiguous physical signs. The subject could complete the PSC on a
Posttreatment Cue Exposure
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TABLE 1 Mean and Standard Deviation of Reaction of Subjects on Slide Cues Before and After Cue Exposure Treatment (CET), Including 6-Week Follow-Up (n 5 16)
Pre-CET
Craving Depression Anger Fatigue Vigor Tension POMS—total Withdrawal-like symptoms Drug-agonistic symptoms Ambiguous symptoms
Post-CET
6-Week Follow-Up
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
0.0 (0.1) 2.1 (3.7) 2.4 (3.7) 2.6 (2.9) 7.9 (3.9) 5.3 (4.5) 15.8 (6.8) 1.7 (1.6) 0.4 (0.6) 2.9 (2.7)
1.0 (1.5)* 3.1 (4.0)* 5.4 (5.0)** 2.4 (3.0) 7.4 (4.2) 3.6 (2.3) 18.9 (9.9)* 2.3 (1.7) 0.6 (0.9) 2.9 (2.8)
0.0 (0.0) 0.4 (1.0) 0.6 (1.8) 1.6 (1.9) 8.2 (3.7) 0.8 (1.5) 11.1 (4.9) 0.9 (1.1) 0.3 (0.6) 0.6 (0.9)
0.1 (0.2) 0.3 (0.8) 1.3 (3.0) 2.1 (2.5) 8.0 (4.5) 0.8 (1.3) 12.4 (5.9) 0.9 (1.4) 0.3 (0.6) 0.5 (0.9)
0.0 (0.0) 0.7 (2.0) 1.3 (2.6) 2.3 (3.4) 8.0 (3.3) 1.6 (2.2) 12.6 (8.2) 1.1 (1.5) 0.1 (0.3) 0.5 (1.1)
0.1 (0.1) 0.7 (2.3) 2.1 (3.2) 2.0 (3.8) 7.4 (4.0) 1.1 (1.6) 13.3 (6.6) 1.0 (1.3) 0.1 (0.3) 0.4 (0.8)
Note. Wilcoxon Matched-Paired Signed-Ranks test (differences on neutral vs. drug cues). * p , .01; ** p , .001.
4-point scale, ranging from 0 (symptom not present) to 3 (symptom strongly present). The craving scale was completed by the subject every minute during presentation of the stimulus. Administration of the POMS and PSC questionnaires took place after each presentation of a neutral or drug-related cue. The same sequence of stimulus presentation was used in each measurement-session (neutral slide, drug slide, neutral video, drug video). Analysis Because of the small sample size and the non-normal distribution of some variables, nonparametric Wilcoxon Matched-Pairs Test was used for analyzing differences on reactivity between neutral and drug cues on baseline measurement. This same statistical test was used to analyze
changes between baseline drug reactivity, posttreatment drug reactivity and 6-week follow-up drug reactivity. RESULTS Pretreatment Differences on Drug Versus Neutral Cues The mean score of the subjects’ reactivity after presenting the slide stimuli is summarized in Table 1. As indicated, Craving (Z 5 1.4; p 5 .018), Depression (Z 5 2.41; p 5 .016), Anger (Z 5 2.94; p 5 .003), and Total score of the POMS (Z 5 2.31; p 5 .021) elicited an increased reaction to the drug-related slides, compared to neutral slides in the pre-CET phase. The mean score of the subjects’ reactivity after presenting the video stimuli is summarized in Table 2. Increased
TABLE 2 Mean and Standard Deviation of Reaction of Subjects on Video Cues Before and After Cue Exposure Treatment (CET), Including 6-Week Follow-Up (n 5 16)
Pre-CET
Craving Depression Anger Fatigue Vigor Tension POMS—total Withdrawal-like symptoms Drug-agonistic symptoms Ambiguous symptoms
Post-CET
6-Week Follow-Up
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
0.0 (0.0) 1.6 (2.9) 2.3 (3.6) 3.3 (4.6) 7.6 (4.4) 3.6 (2.3) 15.2 (7.1) 1.9 (1.6) 0.5 (0.8) 2.4 (2.6)
1.9 (1.5)** 2.8 (4.2)* 6.8 (7.3)** 2.8 (3.3) 7.0 (4.3) 4.4 (4.1) 19.2 (11.8) 3.0 (2.4) 0.6 (0.8) 2.9 (2.6)
0.0 (0.0) 0.3 (0.9) 1.2 (2.4) 2.4 (2.3) 7.6 (4.4) 0.9 (1.5) 12.5 (5.3) 0.9 (1.4) 0.3 (0.6) 0.7 (1.1)
0.1 (0.3) 0.3 (0.9) 2.3 (5.0) 2.2 (2.3) 8.0 (4.4) 1.3 (2.0) 13.1 (6.7) 1.7 (2.2) 0.3 (0.6) 0.9 (1.4)
0.0 (0.0) 0.7 (2.0) 1.3 (2.7) 2.4 (4.4) 7.4 (4.0) 0.9 (1.6) 13.5 (7.7) 0.8 (1.2) 0.3 (0.6) 0.3 (0.6)
0.2 (0.8) 0.6 (1.8) 2.4 (3.1) 2.3 (3.7) 8.4 (3.8) 1.2 (1.4) 12.9 (6.3) 1.3 (1.1) 0.3 (0.6) 0.5 (1.0)
Note. Wilcoxon Matched-Pairs Signed-Ranks test (differences on neutral vs. drug cues). * p , .01; ** p , .001.
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reactivity to the drug-related video was observed, compared to the neutral video in Depression (Z 5 1.93; p 5 .053), Anger (Z 5 2.91; p 5 .004) and Craving (Z 5 3.06; p 5 .002). An increase in withdrawal symptoms after exposure to drug-related video cues was also observed, but this difference was not statistically significant (Z 5 1.79; p 5 .072) at the .05 level. Change of Reactivity After Cue Exposure Treatment The reactivity to the presentation of the drug-related slides, as measured by pre-post CET comparison, decreased for Withdrawal symptoms (Z 5 2.19; p 5 .029), Ambiguous symptoms (Z 5 2.8; p 5 .006), Depression scale (Z 5 2.34; p 5 .02), Tension (Z 5 3.30; p 5 .001), Anger (Z 5 2.66; p 5 .008), POMS-total score (Z 5 2.45; p 5 .014), and Craving (Z 5 2.37; p 5 .018). Cue reactivity on the drug-related slides did not increase after the nine-session CET on any of the measures. Reactivity on the drug-related video stimuli decreased for Withdrawal symptoms (Z 5 2.01; p 5 .045), Ambiguous symptoms (Z 5 2.67; p 5 .008), Depression (Z 5 2.49; p 5 .013), Anger (Z 5 2.06; p 5 .039), Tension (Z 5 2.39; p 5 .017), and Craving (Z 5 3.06; p 5 .002). Like the slide cues, reactivity did not increase on any of the measures following the nine-session CET. Stability of Cue Reactivity After 6-Week Follow-Up To observe the stability of the effects of CET, posttreatment reactivity was compared to 6-week follow-up reactivity. Results indicated that the 6-week follow-up reactivity did not differ (p , .05) from the post-CET reactivity on any of the measures.
drug-free lifestyle (de Leon, 1995), it may be beneficial to incorporate cue exposure as a relapse prevention intervention into these programs. Although, the contribution of self-reported craving and cue reactivity to the occurrence of relapse is still subject of debate in the general field of substance abuse, there is a growing amount of studies in which a relation between cue reactivity and relapse rate in alcohol dependency (Drummond & Glautier, 1994; Kosten, 1992) has been found. There is no unambiguous evidence that the application of cue exposure does in fact prevent relapse in detoxified drug-dependent subjects (Dawe et al., 1993, Powell et al., 1993). In addition, experimental studies on the effect of CET on relapse in posttreatment drug-dependent persons are scarce. In the present study, no control condition was included. Therefore, it remains unclear whether a non-CET intervention would have achieved a similar decrease in cue reactivity. In addition, the sample size is relatively small. Finally, despite the growing amount of studies on cue reactivity and craving, there is still a lack of sound theoretical models. Consequently, the measurement of these phenomena is still subject to discussion (Kozlowski, Pillitteri, Sweeney, Whitfield, & Graham, 1996; Tiffany, 1992). Further research is needed to study the effectiveness of CET in both inpatient and outpatient treatment. With respect to long-term inpatient treatment, the appropriate moment of conducting CET is not known. In addition, further research is needed on the effectiveness of the use of different drug-related stimuli used in CET protocols. The effect of in vivo exposure can be compared to exposure to artificial cues in an experimental design. Finally, the effects of CET should be compared to the effects of other interventions aimed at the reduction of craving, such as pharmacological treatment with naltrexone (Van Ree, 1996).
DISCUSSION The results indicate that, prior to CET, cue reactivity is still present among detoxified patients after 12 months of intensive inpatient treatment. When subjects are confronted with drug-related stimuli, there is an increase in craving and feelings of depression and anger. Given that subjects in the resocialization phase are likely to be confronted with these stimuli (in vivo) soon after treatment discharge, a reduction of cue reactivity may contribute to the prevention of relapse. In the present study, cue reactivity (feelings of depression, anger, tension, craving, and physical symptoms) reduced after CET, and this effect maintained for (at least) 6 weeks after the last CET session. The implications for clinical practice are that cue exposure treatment can reduce self-reported craving in subjects who have been in a long-term inpatient treatment program. Although many therapeutic community treatment programs of drug dependence are focused on changing negative patterns of behavior and promoting a
REFERENCES Childress, A.R., Hole, A.V., Ehrman, R.N., Robbins, S.J., McLellan, A.T., & O’Brien, C.P. (1993). Cue reactivity and cue reactivity interventions in drug dependence. NIDA Research Monograph, 137, 73–95. Childress, A.R., McLellan, A.T., & O’Brien, C.P. (1986). Conditioned responses in a methadone population: A comparison of laboratory, clinic, and natural settings. Journal of Substance Abuse Treatment, 3, 173–179. Dawe, S., Powell, J.H., Richards, D., Gossop, M., Marks, I., Strang, J., & Gray, J. (1993). Does post-withdrawal cue exposure improve outcome in opiate addiction? A controlled trial. Addiction, 88, 1233–1245. de Leon, G. (1995). Therapeutic communities for addictions: A theoretical framework. The International Journal of the Addictions, 30, 1603–1645. Drummond, D.C., & Glautier, S. (1994). A controlled trial of cue exposure treatment in alcohol dependence. Journal of Consulting & Clinical Psychology, 62, 809–817. Glautier, S., & Drummond, D.C. (1994). Alcohol dependence and cue reactivity. Journal of Studies on Alcohol, 55, 224–229. Glautier, S., Drummond, D.C., & Remington, B. (1992). Different
Posttreatment Cue Exposure drink cues elicit different physiological responses in non-dependent drinkers. Psychopharmacology, 106, 550–554. Glautier, S., & Tiffany, S.T. (1995). Methodological issues in cue reactivity research. In D.C. Drummond, S.T. Tiffany, S. Glautier, & B. Remington (Eds.), Addictive behaviour: Cue exposure theory and practice (pp. 75–98). Chichester: John Wiley & Sons. Kosten, T.R. (1992). Can cocaine craving be a medication development outcome? Drug craving and relapse in opioid and cocaine dependence. American Journal on Addictions. 1, 230–239. Kozlowski, L.T., Pillitteri, J.L., Sweeney, C.T., Whitfield, K.E., & Graham, J.W. (1996). Asking about urges or cravings for cigarettes. Psychology of Addictive Behaviors, 10, 248–249. McLellan, A.T., Luborski, L., Woody, G.E., & O’Brien, C.P. (1980). An improved diagnostic evaluation instrument for substance abuse patients: The Addiction Severity Index. The Journal of Nervous and Mental Disease, 168, 26–33. McNair, D., Lorr, M., & Droppelman, L.F. (1971). Profile of mood states. San Diego, CA: Educational and Industrial Services. Niaura, R.S., Rohsenow, D.J., Binkhoff, J.A., Monti, P.M., Pedraza, M., & Abrams, D.B. (1988). Relevance of cue reactivity to understanding of alcohol and smoking relapse. Journal of Abnormal Psychology, 97, 133–152. Powell, J. (1995). Conditioned responses to drug-related stimuli: Is context crucial? Addiction, 90, 1089–1095. Powell, J., Bradley, B., & Gray, J. (1992). Classical conditioning and cognitive determinants of subjective craving for opiates: An investigation of their relative contributions. British Journal of Addiction, 87, 1133–1144. Powell, J., Gray, J., & Bradley, B.P. (1993). Subjective craving for opiates: Evaluation of a cue exposure protocol for use with detoxified opiate addicts. British Journal of Clinical Psychology, 32, 39– 53. Powell, J., Gray, J.A., Bradley, B.P., Kasvikis, Y., Strang, J., Barrat, L.,
85 & Marks, I. (1990). The effects of exposure to drug-related cues in detoxified opiate addicts: A theoretical review and some new data. Addictive Behaviors, 15, 339–354. Powell, J.H., Dawe, S., Richards, D., Gossop, M., Marks, I., Stang, J., & Gray, J. (1993). Can opiate addicts tell us about their relapse risk? Subjective predictors of clinical prognosis. Addictive Behaviors, 18, 473–490. Rees, V.W., & Heather, N. (1995). Individual differences and cue reactivity. In D.C. Drummond, S.T. Tiffany, S. Glautier, & B. Remington (Eds.), Addictive Behavior: Cue exposure theory and practice (pp. 99–118). Chichester: John Willey & Sons Ltd. Robbins, S.J., Ehrman, R.N., Childress, A.R., & O’Brien, C.P. (1992). Using cue reactivity to screen medications for cocaine abuse: A test of amantadine hydrochloride. Addictive Behaviors, 17, 491–499. Siegel, S. (1983). Classical conditioning, drug tolerance, and drug dependence. In Y. Israel, F.B. Glaser, H. Kalant, R.E. Popham, W. Schmidt, & R.G. Smart (Eds.), Research advances in alcohol and drug problems (pp. 207–246). New York: Plenum Press. Staiger, P.K., & White, J.M. (1991). Cue reactivity in alcohol abusers: Stimulus specificity and extinction of the responses. Addictive Behaviors, 16, 211–221. Stewart, J., de Wit, H., & Eikelboom, R. (1984). Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychological Review, 91, 251–268. Tiffany, S.T. (1990). A cognitive model of drug urges and drug-use behavior: Role of automatic and nonautomatic processes. Psychological Review, 97, 147–168. Tiffany, S.T. (1992). A critique of contemporary urge and craving research: Methodological, psychometric, and theoretical issues [Special Issue: Urges and cravings]. Advances in Behaviour Research and Therapy, 14, 123–139. Van Ree, J.M. (1996). Endorphins and experimental addiction. Alcohol, 13, 25–30.
PII S0740-5472(98)00004-X
INTERNATIONAL PERSPECTIVE
Cue Reactivity and Effects of Cue Exposure in Abstinent Posttreatment Drug Users Ingmar H. A. Franken, msc,* Hein A. de Haan, md,† Chris W. van der Meer, md,‡ P. M. Judith Haffmans, phd,* and Vincent M. Hendriks, phd* *Research Department of Psychiatric Centre Bloemendaal, The Hague, The Netherlands †Twents Psychiatric Hospital/IVON, Enschede, The Netherlands ‡Substance Abuse Treatment Unit of Psychiatric Centre Bloemendaal, The Hague, The Netherlands
Abstract – After 12 months of inpatient treatment, 16 opiate-addicted patients were exposed to drugrelated stimuli. The results of this study indicate that cue reactivity in opiate-addicted subjects is still present after 12 months of intensive inpatient treatment. After exposing subjects to drug-related stimuli, there is an increase in craving, feelings of depression, and anger. Because posttreatment subjects are likely to be confronted with these stimuli following discharge, a reduction of this reactivity is desirable. In the present study, cue reactivity (feelings of depression, anger, tension, craving, and physical symptoms) reduced after protocolized cue exposure treatment. This effect maintained for at least 6 weeks after the last cue exposure session. © 1998 Elsevier Science Inc. Keywords – addiction; cue exposure; cue reactivity; opiate dependence; craving.
INTRODUCTION
gel, 1983). Craving, a subjective desire to use the drug of choice, is believed to play an important role in the occurrence of relapse in abstinent drug-addicted persons in their natural setting (Childress, McLellan, & O’Brien, 1986). Besides craving, other subjective cue-elicited reactions have been reported, including subjective withdrawal symptoms, subjective drug-agonistic effects, mood swings, and anxiety (Glautier & Tiffany, 1995; Powell, Gray, & Bradley, 1993). Physiological reactions that have been investigated include skin conductance, heart rate, salivation, and body temperature (Glautier, Drummond, & Remington, 1992). The exact nature of the relation between subjective and physiological signs of reactivity is still subject to debate (Tiffany, 1990). Furthermore, whether the direction of the conditioned response is drug antagonistic (withdrawal) or drug agonistic (drug-like), is still unclear (Stewart, de Wit, & Eikelboom, 1984). Conditioned reactivity to substance-related cues is believed to be an important factor within addictive use of
Cue reactivity to drug related stimuli is a frequently observed phenomenon in drug-dependent subjects (Childress et al., 1993; Powell, Gray, & Bradley, 1993). Cue reactivity refers to a classical conditioned response (CR) that occurs when a (post)addicted subject is exposed to drug-related stimuli (CS). This response is presumed to consist of physiological and/or subjective reactions (SieThis study has been conducted at the Psychiatric Centre Bloemendaal, Substance Abuse Treatment Unit. This research was supported by grants of the “Stichting tot Steun van Vereniging Bennekom” and NFGV (Nationial Fund Mental Health) grant 4325. Thanks are extended to the staff and patients of the Psychiatric Centre Bloemendaal Substance Abuse Treatment Unit for their support. In addition, we thank Irma Huijbrechts, Janet de Vries, and Ada Kwakkelstein for their help in the preparation of the manuscript. Requests for reprints should be addressed to Ingmar Franken, Psychiatric Centre Bloemendaal, Research Department, P.O. Box 53002, 2505 AA The Hague, The Netherlands. E-mail: [email protected]
Received August 15, 1997; Accepted November 5, 1997.
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alcohol (Glautier & Drummond, 1994; Staiger & White, 1991), opiates (Powell et al., 1990), nicotine (Niaura et al., 1988), and cocaine (Robbins, Ehrman, Childress, & O’Brien, 1992). These studies have shown an increase in reactivity when addicted subjects are exposed to drugrelated cues, as compared with exposure to neutral cues. Albeit, individual differences in nature and extent of the cue-elicited response cannot be ignored (Rees & Heather, 1995). Human experimental studies reveal that cue reactivity may still be present after detoxification (Powell et al., 1990). In addition, subjects who have repeatedly been exposed to drug-related cues during their treatment, showed a reduction in cue reactivity. Cue Exposure Treatment (CET) refers to a protocolized, repeated, exposure to drug-related cues, aimed at the reduction of cue reactivity by extinction, a behavior therapy technique. The present study is designed to examine the occurrence and nature of cue reactivity in subjects who have been treated for drug dependence in an intensive, drugfree inpatient treatment program for a minimal period of 12 months. At time of the study, the subjects participated in an outpatient resocialization program. It was hypothesized that cue reactivity, if present, would decrease in this population after a protocolized nine-session CET. Enduring effects of CET were studied by evaluating cue reactivity of the study subjects 6 weeks after the last exposure session.
Subjects The study group consisted of 16 patients who, after clinical detoxification and intensive inpatient treatment for at least 12 months in the drug-free therapeutic community “Emiliehoeve,” participated in the outpatient resocialization phase of the program. All subjects participated voluntarily and signed an informed consent. The inclusion criteria were: age 18–60, opiate dependency according DSM-IV criteria, inhalation (“chasing the dragon”) as primary mode of heroin administration, successful completion of the clinical treatment program, abstinence from any drugs for at least 6 months preceding the study, and adequate understanding of the Dutch language. The 16 persons in the study consisted of 7 female and 9 male subjects. The average number of clinical admissions for the treatment of drug-dependence was two (range 1–8). The mean age of these subjects was 29.5 years (range 20–42). The mean Addiction Severity Index (ASI; McLellan, Luborski, Woody, & O’Brien, 1980) score at intake was 3.3 (SD 5 1.3). The mean severity scores, ranging from no problems (0) to extreme problems (9), on the separate ASI areas were: medical problems 1.6 (SD 5 2.2), employment problems 2.9 (SD 5 2.1), alcohol problems 1.4 (SD 5 2.3), drug problems 5.5 (SD 5 1.0), legal problems 3.9 (SD 5 2.3), social problems 3.3 (SD 5 2.3), and psychiatric problems 4.3 (SD 5 1.7).
I.H.A. Franken et al.
Procedure and Assessments At intake, before detoxification, the ASI (McLellan et al., 1980) was administered to asses the severity of drugrelated problems. After detoxification, all subjects received intensive inpatient treatment for at least 12 months. In the subsequent outpatient resocialization phase of the treatment program, subjects were asked to participate in the CET program. CET consisted of a ninesession, protocolized exposure to drug-related cues. Twelve different stimuli (slides, video, drug-use material, simulation of drug-use ritual) were presented to the subjects during the study. The assessment sessions consisted of the presentation of four different cues (two slides and two videos). Every cue was presented for 5 minutes. The neutral cues consisted of a slide of a landscape and a film of natural scenery (video). The drug cues consisted of a slide of drug users who prepared smokeable heroin and inhaled heroin (“chasing the dragon”) and a film of this ritual (video). The slide and video stimuli were presented to the subjects within the same session. Assessments of reactivity to drug-related and neutral cues were conducted prior to the CET after nine CET sessions (posttreatment), and after 6 weeks following the last CET session (follow-up). These assessments consisted of a (single-item) craving scale, the Profile of Mood States (POMS) and the Physical Symptom Checklist (PSC). The CET and assessment procedure have been described by Powell, Gray, and Bradley (1993). Craving Scale. A single-item self-rating scale was used to assess the intensity of craving each minute during the presentation of the stimuli. The scale ranged from 0 (no craving) to 10 (excessive craving). For each stimulus a mean craving score of the subject was calculated. For purposes of the study, craving was defined as the strength of the attraction to use drugs (Powell,1995). It was explicitly communicated with the subjects that craving could also occur when they felt they were able to resist drug use. Profile of Mood States. The abridged Dutch version of the POMS (McNair, Lorr, & Droppelman, 1971) has acceptable psychometric properties. Five subscales were used in this study (Depression, Anger, Fatigue, Vigor, and Tension). Furthermore, a total score is calculated by adding the scores of the subscales used (the subscale Vigor is recoded). The POMS consisted of 32 items that can be scored on a 5-point scale, from 0 (none) to 5 (extremely intense). Physical Symptoms Checklist. This checklist was adopted from Powell, Bradley, and Gray (1992). The PSC measures physical symptoms that reflect characteristics of opiate withdrawal and drug-agonistic states. Furthermore, a residual category was used to report ambiguous physical signs. The subject could complete the PSC on a
Posttreatment Cue Exposure
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TABLE 1 Mean and Standard Deviation of Reaction of Subjects on Slide Cues Before and After Cue Exposure Treatment (CET), Including 6-Week Follow-Up (n 5 16)
Pre-CET
Craving Depression Anger Fatigue Vigor Tension POMS—total Withdrawal-like symptoms Drug-agonistic symptoms Ambiguous symptoms
Post-CET
6-Week Follow-Up
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
0.0 (0.1) 2.1 (3.7) 2.4 (3.7) 2.6 (2.9) 7.9 (3.9) 5.3 (4.5) 15.8 (6.8) 1.7 (1.6) 0.4 (0.6) 2.9 (2.7)
1.0 (1.5)* 3.1 (4.0)* 5.4 (5.0)** 2.4 (3.0) 7.4 (4.2) 3.6 (2.3) 18.9 (9.9)* 2.3 (1.7) 0.6 (0.9) 2.9 (2.8)
0.0 (0.0) 0.4 (1.0) 0.6 (1.8) 1.6 (1.9) 8.2 (3.7) 0.8 (1.5) 11.1 (4.9) 0.9 (1.1) 0.3 (0.6) 0.6 (0.9)
0.1 (0.2) 0.3 (0.8) 1.3 (3.0) 2.1 (2.5) 8.0 (4.5) 0.8 (1.3) 12.4 (5.9) 0.9 (1.4) 0.3 (0.6) 0.5 (0.9)
0.0 (0.0) 0.7 (2.0) 1.3 (2.6) 2.3 (3.4) 8.0 (3.3) 1.6 (2.2) 12.6 (8.2) 1.1 (1.5) 0.1 (0.3) 0.5 (1.1)
0.1 (0.1) 0.7 (2.3) 2.1 (3.2) 2.0 (3.8) 7.4 (4.0) 1.1 (1.6) 13.3 (6.6) 1.0 (1.3) 0.1 (0.3) 0.4 (0.8)
Note. Wilcoxon Matched-Paired Signed-Ranks test (differences on neutral vs. drug cues). * p , .01; ** p , .001.
4-point scale, ranging from 0 (symptom not present) to 3 (symptom strongly present). The craving scale was completed by the subject every minute during presentation of the stimulus. Administration of the POMS and PSC questionnaires took place after each presentation of a neutral or drug-related cue. The same sequence of stimulus presentation was used in each measurement-session (neutral slide, drug slide, neutral video, drug video). Analysis Because of the small sample size and the non-normal distribution of some variables, nonparametric Wilcoxon Matched-Pairs Test was used for analyzing differences on reactivity between neutral and drug cues on baseline measurement. This same statistical test was used to analyze
changes between baseline drug reactivity, posttreatment drug reactivity and 6-week follow-up drug reactivity. RESULTS Pretreatment Differences on Drug Versus Neutral Cues The mean score of the subjects’ reactivity after presenting the slide stimuli is summarized in Table 1. As indicated, Craving (Z 5 1.4; p 5 .018), Depression (Z 5 2.41; p 5 .016), Anger (Z 5 2.94; p 5 .003), and Total score of the POMS (Z 5 2.31; p 5 .021) elicited an increased reaction to the drug-related slides, compared to neutral slides in the pre-CET phase. The mean score of the subjects’ reactivity after presenting the video stimuli is summarized in Table 2. Increased
TABLE 2 Mean and Standard Deviation of Reaction of Subjects on Video Cues Before and After Cue Exposure Treatment (CET), Including 6-Week Follow-Up (n 5 16)
Pre-CET
Craving Depression Anger Fatigue Vigor Tension POMS—total Withdrawal-like symptoms Drug-agonistic symptoms Ambiguous symptoms
Post-CET
6-Week Follow-Up
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
Neutral M (SD)
Drug M (SD)
0.0 (0.0) 1.6 (2.9) 2.3 (3.6) 3.3 (4.6) 7.6 (4.4) 3.6 (2.3) 15.2 (7.1) 1.9 (1.6) 0.5 (0.8) 2.4 (2.6)
1.9 (1.5)** 2.8 (4.2)* 6.8 (7.3)** 2.8 (3.3) 7.0 (4.3) 4.4 (4.1) 19.2 (11.8) 3.0 (2.4) 0.6 (0.8) 2.9 (2.6)
0.0 (0.0) 0.3 (0.9) 1.2 (2.4) 2.4 (2.3) 7.6 (4.4) 0.9 (1.5) 12.5 (5.3) 0.9 (1.4) 0.3 (0.6) 0.7 (1.1)
0.1 (0.3) 0.3 (0.9) 2.3 (5.0) 2.2 (2.3) 8.0 (4.4) 1.3 (2.0) 13.1 (6.7) 1.7 (2.2) 0.3 (0.6) 0.9 (1.4)
0.0 (0.0) 0.7 (2.0) 1.3 (2.7) 2.4 (4.4) 7.4 (4.0) 0.9 (1.6) 13.5 (7.7) 0.8 (1.2) 0.3 (0.6) 0.3 (0.6)
0.2 (0.8) 0.6 (1.8) 2.4 (3.1) 2.3 (3.7) 8.4 (3.8) 1.2 (1.4) 12.9 (6.3) 1.3 (1.1) 0.3 (0.6) 0.5 (1.0)
Note. Wilcoxon Matched-Pairs Signed-Ranks test (differences on neutral vs. drug cues). * p , .01; ** p , .001.
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reactivity to the drug-related video was observed, compared to the neutral video in Depression (Z 5 1.93; p 5 .053), Anger (Z 5 2.91; p 5 .004) and Craving (Z 5 3.06; p 5 .002). An increase in withdrawal symptoms after exposure to drug-related video cues was also observed, but this difference was not statistically significant (Z 5 1.79; p 5 .072) at the .05 level. Change of Reactivity After Cue Exposure Treatment The reactivity to the presentation of the drug-related slides, as measured by pre-post CET comparison, decreased for Withdrawal symptoms (Z 5 2.19; p 5 .029), Ambiguous symptoms (Z 5 2.8; p 5 .006), Depression scale (Z 5 2.34; p 5 .02), Tension (Z 5 3.30; p 5 .001), Anger (Z 5 2.66; p 5 .008), POMS-total score (Z 5 2.45; p 5 .014), and Craving (Z 5 2.37; p 5 .018). Cue reactivity on the drug-related slides did not increase after the nine-session CET on any of the measures. Reactivity on the drug-related video stimuli decreased for Withdrawal symptoms (Z 5 2.01; p 5 .045), Ambiguous symptoms (Z 5 2.67; p 5 .008), Depression (Z 5 2.49; p 5 .013), Anger (Z 5 2.06; p 5 .039), Tension (Z 5 2.39; p 5 .017), and Craving (Z 5 3.06; p 5 .002). Like the slide cues, reactivity did not increase on any of the measures following the nine-session CET. Stability of Cue Reactivity After 6-Week Follow-Up To observe the stability of the effects of CET, posttreatment reactivity was compared to 6-week follow-up reactivity. Results indicated that the 6-week follow-up reactivity did not differ (p , .05) from the post-CET reactivity on any of the measures.
drug-free lifestyle (de Leon, 1995), it may be beneficial to incorporate cue exposure as a relapse prevention intervention into these programs. Although, the contribution of self-reported craving and cue reactivity to the occurrence of relapse is still subject of debate in the general field of substance abuse, there is a growing amount of studies in which a relation between cue reactivity and relapse rate in alcohol dependency (Drummond & Glautier, 1994; Kosten, 1992) has been found. There is no unambiguous evidence that the application of cue exposure does in fact prevent relapse in detoxified drug-dependent subjects (Dawe et al., 1993, Powell et al., 1993). In addition, experimental studies on the effect of CET on relapse in posttreatment drug-dependent persons are scarce. In the present study, no control condition was included. Therefore, it remains unclear whether a non-CET intervention would have achieved a similar decrease in cue reactivity. In addition, the sample size is relatively small. Finally, despite the growing amount of studies on cue reactivity and craving, there is still a lack of sound theoretical models. Consequently, the measurement of these phenomena is still subject to discussion (Kozlowski, Pillitteri, Sweeney, Whitfield, & Graham, 1996; Tiffany, 1992). Further research is needed to study the effectiveness of CET in both inpatient and outpatient treatment. With respect to long-term inpatient treatment, the appropriate moment of conducting CET is not known. In addition, further research is needed on the effectiveness of the use of different drug-related stimuli used in CET protocols. The effect of in vivo exposure can be compared to exposure to artificial cues in an experimental design. Finally, the effects of CET should be compared to the effects of other interventions aimed at the reduction of craving, such as pharmacological treatment with naltrexone (Van Ree, 1996).
DISCUSSION The results indicate that, prior to CET, cue reactivity is still present among detoxified patients after 12 months of intensive inpatient treatment. When subjects are confronted with drug-related stimuli, there is an increase in craving and feelings of depression and anger. Given that subjects in the resocialization phase are likely to be confronted with these stimuli (in vivo) soon after treatment discharge, a reduction of cue reactivity may contribute to the prevention of relapse. In the present study, cue reactivity (feelings of depression, anger, tension, craving, and physical symptoms) reduced after CET, and this effect maintained for (at least) 6 weeks after the last CET session. The implications for clinical practice are that cue exposure treatment can reduce self-reported craving in subjects who have been in a long-term inpatient treatment program. Although many therapeutic community treatment programs of drug dependence are focused on changing negative patterns of behavior and promoting a
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