Comparison of opioid agonists in maintaining responding and in suppressing morphine withdrawal in rhesus monkeys

Sixteen opioid agonists were studied for their capacity both to maintain responding previously reinforced by codeine and to suppress the withdrawal syndrome induced by morphine deprivation in rhesus monkeys. All compounds, which included examples from each of the major chemical families of opioids, maintained responding at rates above those maintained by saline. There were differences among the compounds in the maximal response rates maintained, and large differences in their potencies in maintaining responding. In morphine-dependent monkeys, the abstinence signs that developed 14 h after the last morphine dose were suppressed completely by all of the compounds except codeine. There was a strong positive correlation (r=0.92) between the potency of a compound in maintaining drug-reinforced responding and the potency of the compound in suppressing the morphine withdrawal syndrome.     

The effects of methadone on operant behavior maintained with and without conditioned reinforcement in the pigeon

Effects of methadone on key pecking supplemented with brief stimuli either correlated with or independent of unconditioned reinforcement was investigated. On average, key pecks by pigeons produced brief stimuli (BS) once per minute and food once per 4 min during both components of a multiple schedule (i.e., VI1:BS, VI4:Food). Brief stimuli were paired with food presentation during one component and not related to food during the second component. Acute methadone administration (0.56, 1.0, 1.7, and 3.0 mg/kg) decreased response rates during both components; however, the decrease was smaller by a constant amount during the paired brief stimulus component, regardless of drug dose. These results suggest conditioned reinforcement is not a primary mechanism through which methadone exerts behavioral effects and that reinforcer-correlated stimuli have potential for diminishing the reduced behavioral output observed following methadone administration.     

Does pregnancy affect outcome of methadone maintenance treatment?

Studies of pregnant women receiving methadone maintenance have tended to focus on teratogenic, prenatal, and neonatal issues. We are not aware of any controlled studies comparing pregnant to non-pregnant heroin-addicted women in methadone treatment. This article presents findings from a study examining treatment outcome between pregnant and non-pregnant participants in a metropolitan methadone-maintenance program. Participants were 51 pregnant women and 51 non-pregnant women enrolled in a methadone maintenance program between 1994 and 2003. Groups were compared on demographic characteristics, psychiatric comorbidity, urinalysis results and retention rates. Groups were comparable in terms of most demographic characteristics and severity of addiction at intake. Groups did not differ significantly in terms of urinalysis results or retention rates. While most women reduced their drug use, a majority of both groups continued to use illicit drugs at least occasionally. Psychiatric comorbidity was significantly different with the non-pregnant group being more psychiatrically disordered. Clinical implications are discussed.     

Improving entry to methadone maintenance among out-of-treatment injection drug users

This study of 577 out-of-treatment drug injectors was designed to assess predictors of methadone maintenance treatment entry, including offering free treatment coupons. Using targeted sampling methods, participants were recruited through street outreach; randomly, they were either assigned a coupon for 90 days of free treatment or required to pay for their treatment. Regardless of assignment, all subjects who desired treatment were provided transportation, rapid intake, and a waiver of the treatment entry fee. Overall, 33% entered treatment, including 66% of those who received a free coupon. Other factors associated with treatment entry included desire for treatment, heroin use, prior treatment experience, associating with fewer drug-using friends, and injecting with a previously used unsterile needle/syringe. Injecting cocaine and smoking crack reduced the probability of treatment entry. Findings lend support to street outreach efforts designed to increase rates of treatment entry among chronic out-of-treatment drug injectors. Additional treatment options are required for those abusing cocaine.     

Nicotine and drug interaction expectancies among methadone maintained cigarette smokers

Smoking rates among persons being treated with methadone for opiate dependence are exceptionally high. Nevertheless, there is debate about whether smoking cessation has a negative effect on substance abuse treatment outcomes. To understand patient perceptions of the interaction between smoking and illicit drug use, we administered the Nicotine and Other Substances Interaction Expectancies questionnaire (NOSIE) to 168 smokers—79% Caucasian and 48% female—at two methadone programs in Providence, Rhode Island. The four summed-rating scales of this 20-item instrument exhibited good to excellent internal-consistency reliabilities. The scales measured the effect of drug use on smoking (5 items, = .84), the effect of smoking on drug use (3 items, = .73), smoking to cope with drug urges (9 items, = .91), and the difficulty of concomitantly quitting smoking and drugs (3 items, = .72).

Most subjects believed drug use increased smoking, but that smoking did not trigger drug use. Relatively few reported smoking to cope with drug urges and most did not consider quitting smoking and quitting drug use to be incompatible goals. NOSIE was a reliable instrument that offers insight into patient expectations of the interaction of smoking and drug use.     

Gaps in the drug-free and methadone treatment program response to Hepatitis C

Drug treatment programs are sites of opportunity for the delivery of hepatitis C (HCV) prevention and care services to drug users. Using data collected from a random nationwide sample (N = 595) of drug treatment programs in the United States, this study compares the provision of HCV services by drug-free and methadone maintenance treatment programs (MMTPs). It then examines and compares perceived inadequacies in this service provision from the perspective of the managers in these two types of programs. Findings indicate that MMTPs are providing more HCV services to their patients, and that a greater proportion of MMTPs are dissatisfied with their current level of HCV service provision. Managers of drug-free programs would like to be offering patients more HCV education, while MMTP managers would like to be providing more HCV testing to their patients, and more support and care for patients who are HCV+.     

Temporal factors affecting cocaine-opioid interactions: a cocaine drug discrimination study in rats

RATIONALE: Increasing concomitant abuse of cocaine and morphine-like opioids has prompted a number of studies aimed at understanding how these drugs interact. OBJECTIVE: The present study was designed to determine if variations in opioid pretreatment time would affect how mu opioid agonists interact with cocaine. METHODS: Rats were trained to discriminate 10 mg/kg cocaine from saline. One group of subjects (n=6) received morphine (5.6 mg/kg) 0.5 h, 1 h or 4 h prior to cumulative doses of cocaine (0.1-17.8 mg/kg). These pretreatment times were selected to overlap with states of acute opioid tolerance (approximately 1 h) or acute opioid dependence (approximately 4 h) as demonstrated by previous studies. A second group (n=6) was administered naloxone (0.3 mg/kg) 5 min prior to cumulative cocaine doses, with or without a 4-h morphine (5.6 mg/kg) or methadone (3.0 mg/kg) pretreatment. In a third procedure, the same subjects used in the second experiment were also tested for time-dependent changes in the analgesic effect of morphine using a hot-plate assay. RESULTS: Morphine pretreatment 1 h prior to assessment of the cocaine dose-response function significantly enhanced the discriminative stimulus effects of cocaine. However, neither 0.5-h or 4-h morphine pretreatment had any effect. In contrast, when naloxone was administered 4 h following either morphine or methadone and 5 min prior to assessment of the cocaine dose-response curve, the discriminative stimulus effects of cocaine were significantly attenuated. In assessing morphine-induced analgesia, paw-lick latency was significantly longer at 1 h and shorter at 4 h following morphine administration. CONCLUSIONS: The results illustrate the importance of temporal parameters for interactions between cocaine and mu opioid agonists.     

Reinforcement by orally delivered methadone, cocaine, and methadone-cocaine combinations in rhesus monkeys: are the combinations better reinforcers?

RATIONALE: Polydrug abuse is a problem that has been infrequently examined. In the present study, drug self-administration procedures were used to investigate the reinforcing effects of drug combinations. OBJECTIVES: To determine the absolute and relative response rates maintained by orally delivered methadone, cocaine, and their combinations under sequential and concurrent access. Choice between drug combinations containing different concentrations of cocaine was also determined. METHODS: Oral intake of methadone, cocaine, and their combinations was studied with rhesus monkeys during daily 3-h sessions. Lip contact (the operant response) was reinforced by delivery of liquid contingent upon completion of a fixed-ratio schedule. In one series, the drugs and drug combinations were studied sequentially with the water vehicle concurrently available. In the next series, the drugs and drug combinations were concurrently available. In the third series, pairs of drug combinations containing different concentrations of cocaine were also concurrently available. RESULTS: Methadone, cocaine and their combinations functioned as reinforcers. Under sequential access, response rates for the drug combinations and the component drugs were often similar. However, under concurrent access, response rates for the drug combinations were greater than response rates for the component drugs at the highest FR size for each condition. Also, drug combinations containing higher cocaine concentrations were preferred to combinations containing lower cocaine concentrations. CONCLUSIONS: Combinations of methadone and cocaine have relatively greater reinforcing effects than the component drugs, and these greater reinforcing effects are better detected with concurrent measures than with sequential measures.     

云南省美沙酮维持门诊服药人员多药滥用及相关影响因素分析

目的了解云南省13个美沙酮门诊受治人员偷吸毒品情况及相关影响因素,旨在减少维持治疗患者的偷吸率及高危行为,完善美沙酮门诊综合干预及服务措施。方法云南省所有美沙酮服药人员,采用横断面调查方法,对云南省美沙酮服药人员进行尿检,检测吗啡及甲基安非他明,并结合个人进行深入访谈。结果吗啡阳性率26.7%,甲基安非他明阳性率12.4%。HIV阴性阳性组偷吸机率相同(P﹥0.05);Logistics回归分析营业时间、门诊收费、治疗剂量、抗病毒治疗知识、入组后使用毒品等为受治者偷吸影响因素(P均﹤0.05)。结论云南省美沙酮受治者主要为文化程度较低中年男性,治疗其间偷吸吗啡及甲基安非他明情况常见;美沙酮门诊服务措施完善及综合干预对减少美沙酮受治者减少偷吸率有重大意义。     

Assessing the effectiveness of an Internet-based videoconferencing platform for delivering intensified substance abuse counseling

Enhanced schedules of counseling can improve response to routine opioid-agonist treatment, although it is associated with increased time demands that enhance patient resistance and nonadherence. Internet-based counseling can reduce these concerns by allowing patients to participate from home. This study assesses treatment satisfaction and response to Internet-based (CRC Health Group's e-Getgoing) group counseling for partial responders to methadone maintenance treatment. Patients testing positive for an illicit substance (n = 37) were randomly assigned to e-Getgoing or onsite group counseling and followed for 6 weeks. Patients in both conditions responded favorably to intensified treatment by achieving at least 2 consecutive weeks of abstinence and 100% attendance to return to less-intensive care (e-Getgoing: 70% vs. routine: 71%, ns). Treatment satisfaction was good and comparable across conditions. E-Getgoing patients expressed a preference for the Internet-based service, reporting convenience and increased confidentiality as major reasons. Integrating Internet-based group counseling with on-site treatment services could help expand the continuum of care in methadone maintenance clinics.