Employment-based reinforcement of adherence to oral naltrexone in unemployed injection drug users: 12-month outcomes.

Oral naltrexone could be a promising relapse-prevention pharmacotherapy for recently detoxified opioid-dependent patients; however, interventions are often needed to promote adherence with this treatment approach. We recently conducted a study to evaluate a 26-week employment-based reinforcement intervention of oral naltrexone in unemployed injection drug users (Dunn et al., 2013). Participants were randomly assigned into a contingency (n = 35) group required to ingest naltrexone under staff observation to gain entry into a therapeutic workplace or a prescription (n = 32) group given a take-home supply of oral naltrexone and access to the workplace without observed ingestion. Monthly urine samples were collected and analyzed for evidence for naltrexone adherence, opioid use, and cocaine use. As previously reported, contingency participants provided significantly more naltrexone-positive urine samples than prescription participants during the 26-week intervention period. The goal of this current study is to report the 12-month outcomes, which occurred 6 months after the intervention ended. Results at the 12-month visit showed no between-groups differences in naltrexone-positive, opioid-negative, or cocaine-negative urine samples and no participant self-reported using naltrexone at the follow-up visit. These results show that even after a period of successfully reinforced oral naltrexone adherence, longer-term naltrexone use is unlikely to be maintained after reinforcement contingencies are discontinued. (PsycINFO Database Record

Response inhibition is impaired by developmental methylmercury exposure: acquisition of low-rate lever-pressing.

Developmental methylmercury (MeHg) exposure produces response perseveration on discrimination reversal procedures, disrupts sensitivity to reinforcement, and enhances sensitivity to dopamine agonists - a profile suggesting a deficit in behavioral inhibition. To examine inhibition, we examined MeHg's effects on the acquisition and persistence of low-rate lever-pressing following a history of high-rate responding. Additionally, we examined whether chronic exposure to selenium protects against MeHg's developmental neurotoxicity. Female rats were exposed in utero via maternal exposure to drinking water containing 0ppm, 0.5ppm or 5ppm of Hg as MeHg, producing approximately 0µg/kg/day, 40µg/kg/day, or 400µg/kg/day of Hg. The mothers (during gestation) and the offspring (throughout life) consumed a purified diet containing 0.06ppm or 0.6ppm of Se (as sodium selenite), forming a 2 (lifespan diet)×3 (developmental MeHg) factorial design. Adult offspring lever-pressed under two schedules of reinforcement. A differential reinforcement of high-rate (DRH) schedule imposed rigid response requirements that remained constant through the study. A high-rate percentile schedule (PCNT-H) incorporated a flexible criterion that reinforced short interresponse times using an adjusting criterion that was sensitive to recent performance. After high-rate responding stabilized, the PCNT-H schedule was abruptly inverted by reinforcing long interresponse times. Acquisition of low-rate responding was impaired in the MeHg-exposed rats because of intrusions of high-rate response bursts. DRH response rates did not change. Dietary selenium did not influence MeHg's effects. High-rate operant behavior perseverated, suggesting that gestational MeHg exposure impairs response inhibition - an effect that extends results previously reported using choice procedures or spatial and visual discrimination reversals.

Employment-based reinforcement of adherence to oral naltrexone treatment in unemployed injection drug users.

Oral naltrexone has high potential for use as a relapse prevention pharmacotherapy for opiate dependence yet suffers from notoriously poor adherence. This study evaluated whether entry to a therapeutic workplace could reinforce adherence with oral naltrexone. Opiate-dependent and cocaine-using injection drug users were detoxified, inducted onto oral naltrexone, and randomly assigned to a contingency (n = 35) or prescription (n = 32) group for a 26-week period. Contingency participants were required to ingest naltrexone under staff observation to gain access to the therapeutic workplace. Prescription participants received a take-home supply of naltrexone and could access the workplace independent of naltrexone ingestion. Primary outcome measures were percent of urine samples positive for naltrexone at 30-day assessments and negative for opiates and cocaine at 30-day assessments. Contingency participants provided significantly more urine samples that were positive for naltrexone compared with prescription participants (72% vs. 21%, p < .01); however, no effect of experimental group was observed on percent opiate-negative (71% vs. 60%, p = .19.) or cocaine-negative (56% vs. 53%, p = .82) samples in the contingency and prescription groups, respectively. Opiate-positive samples were significantly more likely to occur in conjunction with cocaine (p < .001) and when not protected by naltrexone (p < .02), independent of experimental group. Overall, these results show that contingent access to a therapeutic workplace significantly promoted adherence to oral naltrexone, and that the majority of opiate use occurred in conjunction with cocaine use, suggesting that untreated cocaine use may limit the effectiveness of oral naltrexone in promoting opiate abstinence.

Employment-based reinforcement of adherence to depot naltrexone in unemployed opioid-dependent adults: a randomized controlled trial.

AIMS: Naltrexone can be used to treat opioid dependence, but patients refuse to take it. Extended-release depot formulations may improve adherence, but long-term adherence rates to depot naltrexone are not known. This study determined long-term rates of adherence to depot naltrexone and whether employment-based reinforcement can improve adherence. DESIGN: Participants who were inducted onto oral naltrexone were assigned randomly to contingency (n = 18) or prescription (n = 17) groups. Participants were offered six depot naltrexone injections and invited to work at the therapeutic workplace on week days for 26 weeks, where they earned stipends for participating in job skills training. Contingency participants were required to accept naltrexone injections to maintain workplace access and to maintain maximum pay. Prescription participants could work independently of whether they accepted injections. SETTING: The therapeutic workplace, a model employment-based intervention for drug addiction and unemployment. PARTICIPANTS: Opioid-dependent unemployed adults. MEASUREMENTS: Depot naltrexone injections accepted and opiate-negative urine samples. FINDINGS: Contingency participants accepted significantly more naltrexone injections than prescription participants (81% versus 42%), and were more likely to accept all injections (66% versus 35%). At monthly assessments (with missing urine samples imputed as positive), the groups provided similar percentages of samples negative for opiates (74% versus 62%) and for cocaine (56% versus 54%). Opiate-positive samples were more likely when samples were also positive for cocaine. CONCLUSIONS: Employment-based reinforcement can maintain adherence to depot naltrexone. Future research should determine whether persistent cocaine use compromises naltrexone's effect on opiate use. Workplaces may be useful for promoting sustained adherence to depot naltrexone.

Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: a randomized controlled trial.

CONTEXT: Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. OBJECTIVE: To determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. DESIGN: Participants (n = 128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly and developed needed job skills during the first 6 months were hired as operators in a data entry business and assigned randomly to an employment-only (control, n = 24) or abstinence-contingent employment (n = 27) group. SETTING: A non-profit data entry business. Participants Unemployed welfare recipients who used cocaine persistently while enrolled in methadone treatment in Baltimore. INTERVENTION: Abstinence-contingent employment participants received 1 year of employment-based contingency management, in which access to employment was contingent upon provision of drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. MAIN OUTCOME MEASURE: Cocaine-negative urine samples at monthly assessments across 1 year of employment. RESULTS: During the 1 year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment-only participants [79.3% and 50.7%, respectively; P = 0.004, odds ratio (OR) = 3.73, 95% confidence interval (CI) = 1.60-8.69]. Conclusions Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance intervention, and is among the most promising treatments for drug dependence. Work-places could serve as therapeutic agents in the treatment of drug dependence by arranging long-term employment-based contingency management programs.

Attendance rates in a workplace predict subsequent outcome of employment-based reinforcement of cocaine abstinence in methadone patients.

This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N=111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction period, participants provided urine samples but could work independent of their urinalysis results. After the induction period, participants had to provide urinalysis evidence of cocaine abstinence to work and maintain maximum pay. A multiple regression analysis showed that induction period attendance was independently associated with urinalysis evidence of cocaine abstinence under the employment-based abstinence reinforcement contingency. Induction period attendance may measure the reinforcing value of employment and could be used to guide the improvement of employment-based abstinence reinforcement.

Effects of gestational exposure to methylmercury and dietary selenium on reinforcement efficacy in adulthood.

It has recently been demonstrated that developmental exposure to methylmercury (MeHg) is associated with perseveration on operant tasks. An understanding of the behavioral mechanisms underlying this phenomenon may improve human testing of MeHg exposures and could provide insight into clinical syndromes that include perseveration as a component. One possible mechanism is that MeHg-induced enhancement of reinforcer efficacy produces a "reinforcement trap" that inhibits change in novel situations. Rats were exposed gestationally to 0, 0.5 or 5 ppm mercury (Hg) as MeHg via maternal drinking water. They also received a diet during gestation and throughout life that was marginal (0.06 ppm) or rich (0.6 ppm) in selenium (Se), a nutrient believed to protect against MeHg's toxicity. Reinforcer efficacy was evaluated using a progressive ratio schedule of reinforcement during adulthood. Maximum ratio obtained (MRO) was determined using 20 or 60 mg sucrose pellets and with ratio requirements that increased at 5% or 20% per reinforcer. MRO was related to the rate at which the ratio increased, reinforcer magnitude, sex, and exposure regimen; MRO was increased for the 0.6 ppm Se, 5 ppm Hg group. This extends an earlier observation that developmental MeHg exposure enhances reinforcer efficacy, an effect that could be related to reports of perseveration.

Brain and blood mercury and selenium after chronic and developmental exposure to methylmercury.

Fish contain methylmercury and the potentially protective element, selenium. Blood and brain concentrations of these elements were determined in female rats after consuming AIN-93-based diets containing 0.06 or 0.6 ppm of selenium (Se) and drinking water containing 0, 0.5, or 5 ppm of mercury as methylmercury (MeHg) for 6 or 18 months. Brain and blood concentrations of mercury and selenium were also evaluated in neonates after gestational exposure. For adult rats in the high-Se, high-Hg condition, brain selenium content was 0.35 ppm and 1.8 ppm after 6 and 18 months, respectively, but for every other adult-onset condition, it was 0.1 ppm. Blood selenium varied less than two-fold despite a 10-fold difference in diet. After 6 months, mercury content in the brain showed a greater than 10-fold difference between the mercury groups, and interacted somewhat with dietary selenium. After 18 months, no mercury was detected in the brains of the 0.5 ppm groups, and their blood mercury also fell. For the 5.0 ppm groups, brain mercury increased slightly (low Se diet) or several-fold (high Se diet) over that seen at 6 months, and blood mercury also increased. Neonatal selenium concentrations were more labile than adults, and mercury in neonates was generally higher. All animals exposed to 5 ppm of mercury experienced a molar excess of mercury over selenium. Animals exposed to 0.5 ppm mercury showed a balance between mercury and selenium or a selenium excess, depending on the condition.