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. Author manuscript; available in PMC: 2017 Jun 1.
Published in final edited form as: Transl Issues Psychol Sci. 2016 Jun;2(2):192–202. doi: 10.1037/tps0000056

Behavioral factors predicting response to employment-based reinforcement of cocaine abstinence in methadone patients

August F Holtyn 1, Wendy Donlin Washington 2, Todd W Knealing 3, Conrad J Wong 4, Ken Kolodner 1, Kenneth Silverman 1
PMCID: PMC5074559  NIHMSID: NIHMS738694  PMID: 27777965

Abstract

We sought to identify behavioral factors associated with response to an employment-based intervention, in which participants had to provide drug-free urine samples to gain access to paid employment. The present secondary analysis included data from a randomized clinical trial. The trial evaluated whether employment-based reinforcement could decrease cocaine use in community methadone patients. Participants (N=56) in the trial worked in a model workplace for 4 hr every weekday and earned about $10 per hr. After a 4-week baseline, participants were randomly assigned to an Abstinence & Work (n = 28) or Work Only (n = 28) condition and could work for an additional 26 weeks. Abstinence & Work participants had to provide cocaine-negative urine samples to work and maintain maximum pay. Work Only participants only had to work to earn pay. For Work Only participants, cocaine abstinence during baseline and the intervention period were significantly (rs = .72, p <.001) correlated. For Abstinence & Work participants, baseline opiate abstinence was significantly correlated (rs = .59, p <.001) and workplace attendance was marginally correlated (rs = .32, p = .098) with cocaine abstinence during the intervention period. Furthermore, participants who provided over 60% cocaine-negative urine samples during the intervention period (i.e., responders) had significantly higher baseline rates of opiate abstinence (p <.0001) and workplace attendance (p = .042) than non-responders. Employment-based reinforcement of cocaine abstinence may be improved by increasing opiate abstinence and workplace attendance prior to initiating the cocaine-abstinence intervention.

Keywords: Cocaine, opiates, methadone, contingency management, incentives

Methadone maintenance is a widely used (Substance Abuse and Mental Health Services Administration, 2014) and effective treatment for opioid dependence, but ongoing abuse of other substances during methadone treatment is common. Rates of cocaine use are particularly high. Some studies have reported that approximately 50–73% of patients use cocaine during methadone treatment (Black, Dolan, Penk, Robinowitz, & Deford, 1987; Grella, Anglin, & Wugalter, 1997; Magura, Kang, Nwakeze, & Demsky, 1998; Sees et al., 2000). The negative health and social consequences of cocaine use among methadone-maintained patients are particularly problematic. Cocaine use during methadone treatment is associated with poor treatment retention, continued opioid use, and an increased probability of relapse (DeMaria, Sterling, & Weinstein, 2000; Grella et al., 1997; Hartel et al., 1995; Leri, Bruneau, & Stewart, 2003; Magura et al., 1998). In addition to adversely impacting treatment outcomes, cocaine use is associated with increased criminal activity, unemployment, diminished psychosocial functioning, and an increased risk of contracting HIV or other blood-borne infectious diseases (Bandettini Di Poggio et al., 2006; Camacho, Bartholomew, Joe & Simpson, 1996; DeMaria, Sterling, & Weinstein, 2000; Grella et al., 1997; Hartel et al., 1995; Joe & Simpson, 1995; Leri et al., 2003). No pharmacological treatments have been demonstrated to be effective in the treatment of cocaine abuse (Shorter, Domingo, & Kosten, 2015), making psychosocial treatments central to reducing cocaine use.

Contingency management interventions, in which patients receive tangible consequences contingent on providing objective evidence of drug abstinence, are one of the most effective psychosocial approaches for initiating drug abstinence (Dutra et al., 2008; Knapp et al., 2007). These interventions are rooted in laboratory and clinical research demonstrating that drug use is operant behavior that is maintained and modifiable by its consequences (Bigelow & Silverman, 1999). As such, drug use can be reduced by the strategic use of operant reinforcement contingencies. For example, voucher-based abstinence reinforcement is a type of contingency management intervention in which patients receive vouchers for providing drug-free urine samples (Higgins et al., 1991). The vouchers have monetary values and can be exchanged for goods and services. Voucher-based reinforcement has been shown to increase abstinence from a wide range of drugs (Lussier et al., 2006) and has been particularly effective in promoting cocaine abstinence in individuals who use cocaine persistently during methadone treatment (Peirce et al., 2006; Rawson et al., 2002; Silverman et al., 1996; Silverman et al., 1998; Silverman, Stitzer, & Bigelow, 1998; Silverman, Robles, Mudric, Bigelow, & Stitzer, 2004). However, similar to other types of treatments, abstinence reinforcement interventions have not reliably prevented the relapse that commonly occurs over the long term after abstinence reinforcement is discontinued (Silverman, DeFulio, & Sigurdsson, 2012). Thus, long-term maintenance of abstinence contingencies may be needed to promote sustained abstinence (Silverman et al., 2004).

In an effort to develop a practical method for arranging long-term exposure to abstinence reinforcement, Silverman and colleagues have examined the use of employment-based abstinence reinforcement, in which participants are required to provide drug-free urine samples to gain access to a model workplace. In this way, participants can work and earn monetary wages, but only as long as they remain abstinent from drugs. Employment-based abstinence reinforcement has increased opiate and cocaine abstinence in methadone-maintained patients (Holtyn et al., 2014a,b; Silverman et al., 2001; Silverman et al., 2002; Silverman et al., 2007), suggesting that it may be a viable means of applying abstinence reinforcement interventions. However, like other interventions, it has not been effective in all participants. An understanding of why employment-based reinforcement is effective in some individuals and not in others would provide valuable information that could be used to improve treatment efficacy.

In a prior study, Donlin, Knealing, Needham, Wong, and Silverman (2008) identified factors that were associated with responsiveness to an employment-based abstinence reinforcement intervention. They performed a predictor analysis on a sample of 111 cocaine-using methadone patients. Cocaine abstinence, opiate abstinence, and workplace attendance during a contingency-free baseline period were examined as predictors of response to employment-based reinforcement of cocaine abstinence. Donlin et al. (2008) reported that cocaine abstinence and workplace attendance, but not opiate abstinence, during baseline were independently associated with cocaine-negative urine samples during the intervention. However, all participants in Donlin et al.’s study were exposed to the cocaine-abstinence contingency. Thus, it is unclear whether the contingency itself is a moderator of the impact of baseline rates of abstinence and workplace attendance on later abstinence.

The present study sought to examine the generality of Donlin et al.’s (2008) findings and extend those results by including a control condition to assess whether factors associated with cocaine abstinence were dependent on exposure to the cocaine-abstinence contingency. The present study assessed whether baseline rates of abstinence and workplace attendance were related to cocaine abstinence during an intervention period among participants who were and were not exposed to an employment-based cocaine abstinence contingency.

Method

This paper presents a secondary analysis of data collected in a randomized clinical trial that evaluated the effectiveness of employment-based reinforcement of cocaine abstinence in community methadone patients (Silverman et al., 2007). The original report of that trial provides a full description of the methods employed in that study and participant demographic information; the present paper will include details of the methods that are most critical to the secondary analyses being presented.

Participants

Participants (N=78) were enrolled in the clinical trial if they were at least 18 years old, unemployed, enrolled in a methadone maintenance program in Baltimore City, reported using cocaine and intravenous drugs in the 30 days prior to intake, provided a cocaine-positive urine sample, and had visible signs of injection drug use. Individuals with current suicidal ideation or hallucinations were excluded from the study. The Institutional Review Board approved the study protocol and all participants provided written informed consent to participate.

Baseline

Participants in the clinical trial were invited to attend the workplace for a 4-week baseline period, during which they could work for 4 hr every weekday and earn approximately $10 per hr ($8 per hr in base pay and about $2 per hr for performance on training programs). Urine samples were collected and tested for opiates and cocaine on Mondays, Wednesdays, and Fridays; however, participants could work even if their urine samples tested positive for opiates or cocaine. Participants who attended the workplace on at least 50% of the workdays, provided at least two cocaine-positive urine samples, and were still enrolled in methadone treatment at the end of the baseline period were randomly assigned to a Work Only (n = 28) or Abstinence & Work (n = 28) condition. Participants in both conditions were invited to attend the workplace for an additional 26 weeks.

Intervention Period

During the intervention period, Abstinence & Work participants were exposed to an employment-based abstinence reinforcement contingency in which they were required to provide urinalysis evidence of recent cocaine abstinence (i.e., if their urinary benzoylecgonine concentration had decreased by at least 20% per day since the last sample, or if the concentration was ≤ 300 ng/ml) to gain daily access to the workplace and to continue earning the standard base pay rate. If a participant provided a urine sample that did not meet the recent abstinence criteria or failed to provide a required sample, the participant was not allowed to work and his or her base pay was reset to $1 per hr. After a participant’s base pay was reset, it could then increase by $1 per hr each day that the participant met the cocaine abstinence requirement and worked at least 5 min, until it reached the standard pay rate of $8 per hr. Participants in the Work Only condition were allowed to work and earn pay even if their urine samples tested positive for opiates or cocaine. The Work Only participants were included in the present analyses as a control condition to assess whether factors associated with cocaine abstinence were dependent on exposure to the cocaine-abstinence contingency.

Urine Collection Testing

Observed urine samples were collected and tested using the Abbott AxSym® system (Abbott Laboratories, Abbott Park, IL). Urine was tested for the heroin metabolite morphine and the cocaine metabolite benzoylecgonine. If the urinary morphine concentration exceeded 300 ng/ml, the sample was considered positive for opiates. Benzoylecgonine concentration was quantified, and that value was compared to previous samples to determine if there was evidence of recent cocaine use. The sample was considered positive for cocaine if urinary benzoylecgonine concentrations exceeded 300 ng/ml and if the concentration had not decreased by at least 20% since the last sample.

Methadone Treatment

Participants in both the Work Only and Abstinence & Work conditions were enrolled in a methadone treatment program, reported receiving statistically similar average maximum methadone doses at their treatment programs (108 mg and 112 mg, respectively), and provided high rates of methadone-positive urine samples at routine assessments that were conducted every 30 days throughout the study (97% and 94% positive, respectively).

Data Analysis

To examine the relation between cocaine abstinence, opiate abstinence, and workplace attendance in the baseline period and cocaine abstinence during the intervention period, we identified three primary baseline measures and one primary outcome (i.e., intervention period) measure. The three primary baseline measures were the percentage of thrice-weekly urine samples that were negative for cocaine and opiates (a 4-week period totaling 12 measurements), and the percentage of available minutes that participants worked during baseline. The percentage of minutes worked was calculated as total minutes worked during the 4 weeks of the induction period divided by 4,800 min, the maximum possible number of minutes in that period (240 min per day times 20 days). The primary outcome measure was the percentage of thrice-weekly urine samples that participants provided during the 26-week intervention period that were negative for cocaine (a total of 78 measures). Urine samples were considered negative for opiates and cocaine if the concentration of the metabolite, morphine or benzoylecgonine, respectively, was ≤ 300 ng/ml. Data were aggregated for each participant to provide one value for each baseline measure and one value for the outcome measure. Because of the skewed non-normal distributions of some of the outcome measures, Spearman’s correlation coefficients were calculated to assess the relation between each of the baseline variables and the primary outcome measure (the percentage of cocaine-negative urine samples) for each of the study conditions (the Work Only condition and the Abstinence & Work condition).

For the urinalysis measures, missing samples were considered positive. Additional analyses were conducted in which two other methods were used to handle missing urinalysis samples. Values were interpolated based on the urinalysis results before and after the missing sample, and values were not replaced. The results of those analyses were similar to the primary analyses in which missing samples were considered positive. Furthermore, adjusted logistic regression analyses reported previously showed no significant between-group differences in the percentage of urine samples collected during the induction and intervention periods (see Silverman et al., 2007 for rates of missing urine samples). Therefore, only the primary analyses will be presented.

Exploratory analyses using similar procedures were used to examine two other baseline measures of cocaine use (average and maximum benzoylecgonine concentration during baseline) and another measure of the reinforcing value of the workplace (the percentage of available days that participants worked during baseline). In addition, the three primary baseline measures were analyzed as independent variables using a least squares linear multiple regression to determine the independent relation between each of the baseline variables and the primary outcome variable.

The original study on which this secondary analysis was based (Silverman et al., 2007) found a bimodal distribution for the intervention period percentage of cocaine-negative urine samples in the Abstinence & Work condition: participants either achieved substantial amounts of abstinence (i.e., they provided 69–99% cocaine-negative urine samples), or they failed to achieve substantial abstinence and appeared similar to the control participants (i.e., they provided 0–47% cocaine-negative urine samples). To determine if participants who achieved substantial amounts of abstinence (i.e., “Responders”) differed from participants who did not achieve substantial amounts of abstinence (i.e., “Non-responders”), data from the Responders and Non-responders were compared on the three primary measures assessed during the baseline period. Six participants in the Abstinence & Work condition and one participant in the Work Only condition were categorized as Responders. Because there was only one Responder in the Work Only condition, comparison of Responders and Non-responders on the baseline measures in that condition was not possible. For the Abstinence & Work condition, Levene’s test for equality of variances was used to determine whether group variances for Responders and Non-responders were sufficiently similar to conduct independent-samples t-tests for each baseline measure. For the baseline measures that did not pass Levene’s test, Welch’s t-tests were performed.

Results

Relation Between Baseline Measures and Intervention-Period Cocaine Abstinence

The percentage of cocaine-negative urine samples in the baseline period (Figure 1, top panels; Table 1) was strongly and significantly correlated with the percentage of cocaine-negative urine samples in the intervention period for the Work Only condition, but not the Abstinence & Work condition. The percentage of opiate-negative urine samples during the baseline period (Figure 1, middle panels; Table 1) was correlated with cocaine abstinence during the intervention period in the Abstinence & Work condition, but not in the Work Only condition. The percentage of minutes worked in the baseline period (Figure 1, bottom panels; Table 1) was not significantly correlated with the percentage of cocaine-negative urine samples during the intervention for either condition.

Figure 1.

Figure 1

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The relation between each of the three primary baseline measures (x-axes) and the percentage of cocaine-negative urine samples collected during the intervention period (y-axes) for the Work Only (left column; n=28) and the Abstinence & Work (right column; n=28) conditions. The filled circles show data from individual participants.

Table 1.

Spearman’s r correlation matrix of abstinence-related measures and workplace attendance.

Intervention
Cocaine Negative		 BL Cocaine
Negative		 BL Avg
BZE		 BL Max
BZE		 BL Opiate
Negative		 BL Minutes
Worked
Work Only (n = 28)
BL Cocaine Negative 0.72***
BL Average BZE −0.68*** −0.49**
BL Max BZE −0.51** −0.24 0.92***
BL Opiate Negative 0.29 0.31 −0.24 −0.10
BL Minutes Worked 0.14 0.13 0.15 0.15 0.31
BL Days Worked 0.13 0.24 −0.09 −0.05 0.57** 0.67***
Abstinence & Work (n = 28)
BL Cocaine Negative 0.19
BL Average BZE −0.25 −0.57*
BL Max BZE −0.24 −0.49* 0.92**
BL Opiate Negative 0.59*** 0.03 −0.04 −0.04
BL Minutes Worked 0.32 0.36 −0.20 −0.07 0.47*
BL Days Worked 0.23 −0.02 −0.06 0.02 0.70*** 0.65***
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Note:

*

p < .05;

**

p <. 01;

***

p < .001. BL = Baseline, Avg = Average, BZE = Benzoylecgonine concentration

Table 1 shows results of the exploratory analyses using two other baseline measures of cocaine use (average and maximum benzoylecgonine concentration during baseline) and another measure of the reinforcing value of the workplace (the percentage of available days that participants worked during baseline). The exploratory analyses were generally similar to the analyses using the primary measures of cocaine use (percentage of cocaine-negative urine samples) and the reinforcing value of the workplace (percentage of minutes worked).

Interpretation of the relation between the three primary baseline measures and intervention-period cocaine abstinence is limited by the inter-relations between the baseline measures. Specifically, the percentage of minutes that Abstinence & Work participants worked was significantly correlated with the percentage of opiate-negative urine samples that they provided during the baseline period (Table 1). To determine whether the primary baseline measures were independently associated with the percentage of cocaine-negative urine samples in the intervention period, all variables were included in a multiple regression analysis (Table 2). For the Work Only condition, only the baseline percentage of cocaine-negative urine samples was significantly related to the percentage of cocaine-negative urine samples during the intervention. For the Abstinence & Work condition, only the baseline percentage of opiate-negative urine samples was significantly related to the percentage of cocaine-negative urine samples during the intervention.

Table 2.

Multiple regression analysis for the three primary baseline measures and the primary outcome measure (percentage of cocaine-negative urine samples during the intervention period).

Work Only (n=28) Abstinence & Work (n=28)
Variable Adjusted
beta β		 S.E. p-value Adjusted
beta β		 S.E. p-value
Baseline Cocaine Negative 0.62 0.18 .002 0.68 0.37 .077
Baseline Opiate Negative 0.03 0.09 .780 0.55 0.20 .013
Baseline Minutes Worked 0.34 0.23 .150 0.21 0.51 .688
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Differences in Baseline Measures Between Responders and Non-Responders

Figure 2 shows the distribution of the three primary baseline measures for participants in the Abstinence & Work condition who did (Responders) and did not (Non-responders) achieve substantial amounts of cocaine abstinence during the intervention period. Responders and Non-responders in the Abstinence & Work condition did not differ in the percentage of cocaine-negative urine samples that they provided during the baseline period. In contrast, Responders had significantly higher baseline rates of opiate-negative urine samples and minutes worked compared to Non-responders.

Figure 2.

Figure 2

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The percentage of cocaine-negative urine samples, opiate-negative urine samples, and minutes worked during baseline for Non-responders (n=22) and Responders (n=6) in the Abstinence & Work condition. Participants who provided cocaine-negative urine samples on more than 60% of the urine collection opportunities during the intervention period were categorized as Responders; all others were categorized as Non-responders. Filled circles represent individual participants and the grey horizontal lines represent group means.

Discussion

Employment-based abstinence reinforcement can promote cocaine abstinence; however, it is not effective in all individuals. The analysis reported here identified behavioral factors that were associated with response to employment-based reinforcement of cocaine abstinence among methadone-maintained patients. Opiate abstinence was the most robust predictor of response to the employment-based abstinence contingency. Specifically, Abstinence & Work participants with the highest rates of opiate abstinence during the baseline period were most likely to respond to an intervention that arranged employment-based reinforcement of cocaine abstinence. This behavioral predictor was specific to participants who were exposed to the employment-based abstinence contingency, as similar predictors were not identified for Work Only participants even though rates of abstinence during baseline were statistically similar among participants in the two conditions. Thus, it does not appear that mere exposure to paid employment in the workplace, but rather the abstinence contingency, contributed to this behavioral predictor.

The relation between baseline opiate use and responsiveness to abstinence-reinforcement interventions has been observed previously among populations of cocaine-using methadone patients. Specifically, those patients who had higher rates of opiate abstinence were more likely to achieve high rates of cocaine abstinence when exposed to voucher-based reinforcement of cocaine abstinence (Silverman et al., 1996; 1998). This may reflect the inherent challenge in promoting abstinence from one drug when abuse of other substances is occurring. Opiate abstinence was not identified as a predictor of response to employment-based abstinence reinforcement in Donlin et al.’s (2008) study. However, most participants in that study had high rates of opiate abstinence during the baseline period (96% of the urine samples were negative for opiates). The small amount of variation in rates of opiate abstinence during baseline may have precluded the ability to detect a relation between baseline opiate abstinence and subsequent cocaine abstinence in Donlin et al.’s study.

Cocaine use during baseline was not a behavioral predictor of response to employment-based reinforcement of cocaine abstinence. The majority of participants in the Work Only condition provided low rates of cocaine-negative urine samples during baseline and continued to provide low rates during the intervention period. Abstinence & Work participants provided similarly low rates of cocaine-negative urine samples during baseline; however, several participants provided more cocaine-negative urine samples during the intervention. Thus, while cocaine use was likely to persist at a similar rate in the absence of an intervention, it appears that the cocaine-abstinence contingency overrode this effect. This finding is consistent with prior research suggesting that abstinence-based incentives can improve drug-use outcomes among methadone patients irrespective of the severity of baseline stimulant use (Stitzer et al., 2007).

Baseline rates of workplace attendance were also examined as a predictor of response based on previous basic and clinical research on reinforcement. This research suggests that the duration of time that an individual attends the workplace during a period of unconstrained access may provide a measure of the reinforcing value of employment for that individual (Donlin et al., 2008; Premack, 1959; Timberlake and Farmer-Dougan, 1991). This measure, in turn, may predict the extent to which contingent access to the workplace will serve as a reinforcer for individual participants. In the present study, the correlation between baseline minutes worked and cocaine abstinence in the intervention period for Abstinence & Work participants was not significant, but was similar to the relation reported by Donlin and colleagues (rs = 0.32 versus rs = 0.35, respectively). Furthermore, Responders in the present study had significantly higher amounts of workplace attendance during baseline than Non-Responders. These results are consistent with Donlin et al. (2008) who showed that Responders (individuals who sustained cocaine abstinence for at least three weeks) worked significantly more during baseline than Non-responders (those unable to establish three weeks of sustained cocaine abstinence). Thus, employment-based abstinence reinforcement may be most effective in individuals who maintain high, consistent rates of workplace attendance prior to the initiation of the abstinence contingencies.

Potential conclusions from the data in this study are limited by two main factors. First, the observed relations were descriptive associations, as opposed to experimentally controlled variables. We cannot know for certain whether high rates of opiate abstinence and workplace attendance make participants more responsive to the employment-based reinforcement intervention, or whether those behaviors are simply associated with some unknown factor that influences response to the intervention. Nevertheless, these behavioral factors could be systematically controlled in future studies, which would allow for an experimental analysis of these associations. Second, while workplace attendance was not independently associated with cocaine abstinence during the intervention period, this finding may have been influenced by the criteria for completing the induction period. Recall that participants were required to attend the workplace on at least 50% of the workdays to complete induction and thus qualify for the main study. The attendance requirement may have precluded the ability to detect a significant relation between workplace attendance and subsequent cocaine abstinence, as individuals not attending at least 50% of the workdays were excluded from the study. Nevertheless, the finding that Responders attended the workplace during the baseline period significantly more than Non-responders confirms the relevance of workplace attendance as a predictor of the effectiveness of employment-based abstinence reinforcement.

The present analyses provide information that could be used to improve the effectiveness of employment-based abstinence reinforcement interventions. They suggest that it may be possible to identify responsive and nonresponsive patients prior to implementing the employment-based intervention. For potentially responsive patients, the intervention could be implemented immediately following baseline. In comparison, for potentially nonresponsive patients, measures could be undertaken to increase opiate abstinence and workplace attendance before arranging the cocaine-abstinence intervention. Opiate abstinence could be increased by manipulating each patient’s methadone dose and by arranging a reinforcement contingency for opiate abstinence. Workplace attendance could be increased by increasing the reinforcing value of the workplace, such as by changing the type of work to meet each patient’s interests and by increasing the base pay rate. Tailoring the implementation of the employment-based intervention in this manner may benefit a greater majority of individuals who use cocaine persistently during methadone treatment.

While the present analyses focused on cocaine-using, methadone-maintained patients, the treatment approach described in the present paper has the potential to be widely applied and disseminated. Employment-based reinforcement contingencies could be embedded into real-world workplaces, as workplaces have features that make them ideal vehicles for administering and financing this type of intervention. First, employees maintain regular and extended contact with their places of employment, which could facilitate long-term treatment. Second, naturally-occurring workplace reinforcers (e.g., wages, employee benefits) could be used to reinforce therapeutic behavior change and, in turn, would cover the cost of the financial incentives. Finally, established infrastructures for monitoring employee behavior (e.g., employee wellness programs, workplace drug testing procedures) could be co-opted in the application of employment-based reinforcement. Because workplaces are ubiquitous, diverse populations and behavioral problems could be targeted by this approach. Nevertheless, the present findings also highlight that employers in therapeutically oriented workplaces may need to manipulate parameters of the employment conditions for certain employees in an effort to increase the effectiveness of employment-based reinforcement contingencies.

All substance abuse treatments fail to succeed with some proportion of individuals, and abstinence-reinforcement interventions are no exception. Understanding why interventions fail to affect some individuals and developing methods to remediate those failures is an important challenge for treatment researchers. This study suggests that among persistent cocaine users enrolled in methadone treatment, those with the lowest rates of opiate abstinence and the lowest rates of workplace attendance are least likely to respond to employment-based reinforcement of cocaine abstinence. These relations are orderly at a theoretical level and potentially addressable at a practical level. Future research may build on these findings to improve the effectiveness of employment-based abstinence reinforcement interventions.

Acknowledgments

The preparation of this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Numbers R01 DA037314, R01 DA019497, R01 DA13107, and T32 DA07209. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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