Search PubMed⌕ Search

Biomedical subjects

Walter Ling

Publications and source records attributed to Walter Ling.

At least 37 records · Page 2Linked to original sources
PubMed2004

Participants receiving dehydroepiandrosterone during treatment for cocaine dependence show high rates of cocaine use in a placebo-controlled pilot study.

Twenty-three cocaine-dependent participants were randomly assigned to receive either dehydroepiandrosterone (DHEA; n = 11; 100 mg/day) or placebo (n = 12) in the context of 12 weeks of thrice weekly cognitive-behavioral group counseling. Outcomes were retention, urine drug screening, cocaine craving, adverse experiences, and medication compliance. DHEA-treated participants averaged 45.8 (SD = 28.8) days in treatment, compared with 70.7 (SD = 20.6) days for placebo, r(21) = -2.4, p =.03, and provided 26.8% (SD = 29.3) of urine samples free of cocaine metabolite compared with 70.6% (SD = 39.9) for the placebo condition, r(21) = -3.0, p =.01. No differences were detected between conditions for cocaine craving or adverse experiences. High levels of medication compliance were documented. Results argue against using high doses of DHEA as a pharmacotherapy for cocaine dependence.

Adolescent↗
PubMed2004

Diffusion of substance abuse treatment: will buprenorphine be a success?

The availability of buprenorphine promises to return the treatment of heroin addiction to mainstream medicine in the United States for the first time in nearly a century. This new treatment also provides an opportunity to reflect on the introduction of methadone and LAAM and their subsequent successes and failures in clinical implementation. The three articles that follow in this issue highlight the potential pharmacological, clinical, and logistic advantages of buprenorphine and provide clinicians with guidelines for its use in an integrated treatment setting. The clinical success of buprenorphine, however, depends in large part on factors beyond its pharmacological advantages. Clinician attitude and the extent to which they embrace buprenorphine will play an important role in determining the future success of this medication.

Buprenorphine↗
PubMed2004

Bringing buprenorphine-naloxone detoxification to community treatment providers: the NIDA Clinical Trials Network field experience.

In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16 mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence.

Administration, Sublingual↗
PubMed2003

Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.

BACKGROUND: Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. RESULTS: The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated. CONCLUSIONS: Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.

Administration, Sublingual↗
PubMed2003

Clinical efficacy of buprenorphine: comparisons to methadone and placebo.

Buprenorphine has been studied extensively since 1978 when it was initially proposed as an alternative to methadone for treatment of opioid dependence. Early work by Jasinski et al., 1978; Mello and Mendelson, 1980; Mello et al., 1982; Mello et al., 1983 and Mendelson et al., 1984 and their colleagues demonstrated buprenorphine's low physical abuse potential and its ability to substitute for heroin and reduce heroin self-administration in opiate-dependent humans. The subsequent early clinical studies suggested that, in clinical settings, buprenorphine was a safe and efficacious opiate dependence pharmacotherapy. Formal approval for general clinical use, however, required that systematic data be gathered on buprenorphine's safety and efficacy in larger groups and a series of controlled clinical trials was designed to evaluate its utility from a medication development perspective. In general, these trials adhered to one of three basic protocol designs: comparison of buprenorphine to methadone; dose comparisons using dose response as an indicator of efficacy; and comparison of buprenorphine to placebo. Retention in treatment, reduction in illicit drug use and craving, and patient and staff ratings of improvements were the most frequently used outcome indicators in these trials. Additional data collected included optimum dosing and dosage schedules, adverse reactions and common side-effects, and other information intended to clarify buprenorphine's benefit-risk relationship and to help prepare guidelines for its safe marketing and utilization by physicians in general clinical practice. This paper presents a review of the buprenorphine/methadone comparison trials conducted in the United States and two such trials conducted in Europe. Also reviewed are three placebo-controlled trials and a buprenorphine/methadone detoxification study. Overall, this series of studies did firmly establish the efficacy of buprenorphine alone and in comparison to methadone.

Buprenorphine↗
PubMed2003

Opioid effects and opioid withdrawal during a 24 h dosing interval in patients maintained on buprenorphine.

In maintenance patients methadone has been shown to produce considerable changes in opioid effects and withdrawal over the dosing interval. As a partial agonist buprenorphine may be expected to produce smaller changes, but the nature and magnitude of these changes have only been described for single doses. In the present study opioid effects and withdrawal were described in patients maintained on buprenorphine. Twenty four opioid dependent subjects were administered 16 mg buprenorphine tablets sublingually for 10 days. On day 10 plasma samples were collected and physiological, subjective and observer-rated measures collected pre-dose and at 14 time points during the dosing interval. No significant respiratory depression was observed. Consistent with the partial agonist properties of buprenorphine, other physiological and subjective changes were also of small magnitude. However, even at a once daily dose of 16 mg some patients experienced significant opioid withdrawal that was maximal at the end of the dosing interval. Buprenorphine maintenance should be associated with a high level of safety and a low level of disruption caused by changing opioid effects over the dosing interval, but some patients may require high doses or other strategies to completely suppress withdrawal.

Administration, Sublingual↗
PubMed2003

Irritability following abstinence from cocaine predicts euphoric effects of cocaine administration.

This study evaluated the association between negative affective symptoms during initial abstinence and euphorigenic response to experimentally administered cocaine. Cocaine-dependent individuals achieved 5 days of abstinence in a hospital setting. Forty milligrams of cocaine was given intravenously on the fifth day of abstinence, and participants were asked to rate the subjective effects produced by the drug. The associations between irritability, self-reported depression, and the subjective "high" produced by cocaine were evaluated. Increased levels of irritability and depression both correlated positively and statistically significantly with heightened response to experimentally administered cocaine as indexed by self-reported subjective "high." The positive association between irritability and subjective "high" remained after controlling for self-reported depressive symptoms. The opponent process model predicts that increased levels of negative affect should be associated with diminished euphoric response to cocaine; however, the opposite was observed. If these findings are replicated in a larger sample, then it may be necessary to reconsider the applicability of the opponent process model to cocaine addiction in humans.

Adult↗
PubMed2003

Quantitative EEG abnormalities in recently abstinent methamphetamine dependent individuals.

OBJECTIVE: Methamphetamine exposure is associated with long-lasting reductions in markers for dopaminergic neurons in preclinical models and probably in humans. Quantitative electroencephalography (EEG) has been used to characterize abnormalities in brain function in a number of disorders, including cocaine dependence, but this technique has not been used to characterize abnormalities associated with methamphetamine dependence. METHODS: The sample included 11 methamphetamine dependent subjects and 11 non-drug using volunteers. Methamphetamine dependent subjects were hospitalized for 4 days to document abstinence; non-drug using volunteers were studied as outpatients. EEGs were recorded in the eyes-closed resting state, and absolute EEG power in each frequency band (0.5-4, 4-8, 8-12, and 12-20 Hz) was quantitated using a fast Fourier transform. EEG power was log-transformed prior to analysis. Conventional, EEG tracings were interpreted by a qualified electroencephalographer who was blinded to the subjects' identity. RESULTS: Methamphetamine dependent volunteers with 4 days of abstinence had increased EEG power in the delta and theta bands. Power in the alpha and beta bands did not differ between the groups. Within the methamphetamine dependent group, a majority of the conventional EEGs were abnormal (64%), compared to 18% in the non-methamphetamine using group. CONCLUSIONS: Recently abstinent methamphetamine dependent subjects demonstrate QEEG abnormalities that are consistent with a generalized encephalopathy. SIGNIFICANCE: Encephalopathic changes in brain electrical activity, as found here in methamphetamine dependence, are frequently associated with a range of cognitive and psychiatric abnormalities, suggesting further avenues of investigation.

Adult↗
PubMed2003

Effect of oral ketorolac and gender on human cold pressor pain tolerance.

1. Although the analgesic effect of opioids on experimental cold pressor (CP) pain has been well demonstrated, the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs) on experimental CP pain has been less reliable, a finding complicated by inconsistencies in how CP analgesic effect is measured. 2. In the present study, a clinically relevant CP response of pain tolerance was used to assess the previously undescribed analgesic efficacy of the potent NSAID ketorolac (10 mg, p.o.), on CP pain across gender in a sample of normal subjects (n = 50). 3. Using a placebo-controlled crossover design, neither a main nor interaction effect for ketorolac on CP pain tolerance was detected. When examined by gender, male subjects exhibited a large placebo response to CP pain under study conditions, whereas women (albeit less pain tolerant at baseline) evidenced no placebo effect but a modest-to-good NSAID analgesic response. 4. Findings on the gender-specific placebo and analgesic NSAID response, integrated with the current literature, indicate that the lack of NSAID analgesic efficacy in the CP pain model may be related to unexamined and differential effects of how gender affects NSAID analgesic effect.

Administration, Oral↗
PubMed2003

Opiate recidivism in a drug-treatment program: comparison of hair and urine data.

The objective of this preliminary study was to determine whether hair can be used as an adjunct specimen for the monitoring of opiate use in a drug-treatment program. Subjects (n = 10) initiating clinical therapy for opiate addiction were monitored for up to 17 weeks with hair and urinalysis. Questionnaires were administered weekly to document hair cuts and chemical treatments. Hair specimens were collected weekly by cutting at the scalp and segmented into 1-cm lengths prior to analysis. Codeine (COD), morphine (MOR), and 6-monoacetylmorphine (6-MAM) concentrations in hair were measured by liquid chromatography-mass spectrometry (LC-MS) [limit of detection (LOD): 20 pg/mg for COD and 6-MAM; 50 pg/mg MOR]. Urine specimens were analyzed by semiquantitative radioimmunoassay (25-ng/mL cutoff) and LC-MS for codeine (COD), morphine (MOR), morphine-3beta-glucuronide (M3G), morphine-6 beta-glucuronide (M6G), and 6-monoacetylmorphine (6-MAM). The LOD and limit of quantitation (LOQ) in urine for COD, M3G, M6G, and 6-MAM were 10 ng/mL and 25 ng/mL for MOR. Interpretation of the segmental hair data in this study was complex and generally was not in agreement with urine data in most cases. Evaluation of hair data suggested that 6 of 10 subjects discontinued opiate use by the end of the study, whereas 3 of 10 appeared to have reduced their use. One subject appeared not to have used opiates throughout the entire study. In contrast, evaluation of urine data suggested that only 4 of 10 subjects significantly reduced use, and 6 of 10 continued drug use on at least an intermittent basis. Urine appeared to be a more sensitive indicator of changes in the pattern(s) of drug use during the course of clinical drug treatment.

Adolescent↗
PubMed2003

Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use.

BACKGROUND: This screening trial evaluated whether the GABAB agonist baclofen demonstrated sufficient clinical efficacy to recommend an adequately powered trial of the medication as a pharmacotherapy for cocaine dependence. METHOD: Participants with cocaine dependence verified by the Structured Clinical Interview for DSM-IV were randomly assigned to baclofen (N = 35; 20 mg t.i.d.) or placebo conditions (N = 35; identical in appearance and dosage rate) using a 2-group, experimental, 16-week double-blind design featuring thrice-weekly cognitive-behavioral drug counseling groups. Outcomes were retention, cocaine use, cocaine craving, and adverse events. RESULTS: A generalized estimating equation (GEE) model showed that participants assigned to receive baclofen demonstrated statistically significant reductions in cocaine use over those assigned to receive placebo as indicated by urine drug screening results (chi(2) = 5.34, df = 1, p =.021). Confirming the GEE model, longitudinal analyses showed that participants assigned to receive baclofen demonstrated significant and stepwise increases in the probability of providing benzoylecgonine-free urine samples throughout the trial as the number of benzoylecgonine-positive samples increased during baseline (chi(2) = 10.63, df = 1, p =.001). Participants assigned to placebo demonstrated no such association. Univariate analyses of aggregates of urine drug screening showed generally favorable outcomes for baclofen, but not at statistically significant levels. There was no statistical significance observed for retention, cocaine craving, or incidence of reported adverse events by treatment condition. CONCLUSIONS: Project findings demonstrated initial clinical efficacy of baclofen over placebo in reducing cocaine use when delivered concurrent with thrice-weekly drug abuse counseling sessions. The effects of baclofen were particularly apparent for those participants with chronic levels of cocaine use at baseline and provide support for a full-scale efficacy trial for baclofen, especially among this subgroup of patients.

Adult↗
PubMed2002

A screening trial of amantadine as a medication for cocaine dependence.

This screening trial evaluated whether amantadine hydrochloride (100 mg bid) demonstrated sufficient clinical efficacy compared to placebo to recommend development as a pharmacotherapy for cocaine dependence. Participants were randomized to amantadine (n=34) or placebo (n=35) conditions in a 16-week, placebo-controlled, double blind trial with three times per week group counseling. Amantadine-treated participants were retained significantly longer than placebo. Based on results of a joint probability index for urine drug testing results (i.e. the proportion of cocaine-metabolite free urine samples divided by the number of participants assigned to the condition), participants assigned to amantadine were found to be significantly more likely to be cocaine abstinent on the last day of 8-weeks of treatment than participants assigned to placebo. Results at the end of 16 weeks of treatment were similar. Standard measures of urine drug testing consistently favored the amantadine condition over placebo, although not at levels of statistical significance. There was no statistical significance infrequency or severity of reported adverse events by treatment condition. Participants assigned to amantadine exhibited greater reductions in global staff ratings of cocaine dependence severity from baseline to termination compared with placebo. There were no significant differences in frequency or severity of reported adverse events by treatment condition. These results provide moderate support for further study of amantadine for the treatment of cocaine dependence.

Adult↗
PubMed2002

A comparison of contingency management and cognitive-behavioral approaches during methadone maintenance treatment for cocaine dependence.

BACKGROUND: This study compared 2 psychosocial approaches for the treatment of cocaine dependence: contingency management (CM) and cognitive-behavioral therapy (CBT). METHODS: Patients with cocaine dependence who were receiving methadone maintenance treatment (n = 120) were randomly assigned to 1 of 4 conditions: CM, CBT, combined CM and CBT (CBT + CM), or treatment as usual (ie, methadone maintenance treatment program only [MMTP only]) (n = 30 per cell). The CM procedures and CBT materials were comparable to those used in previously published research. The active study period was 16 weeks, requiring 3 clinic visits per week. Participants were evaluated during treatment and at 17, 26, and 52 weeks after admission. RESULTS: Urinalysis results during the 16-week treatment period show that participants assigned to the 2 groups featuring CM had significantly superior in-treatment urinalysis results, whereas urinalysis results from participants in the CBT group were not significantly different than those from the MMTP-only group. At week 17, self-reported days of cocaine use were significantly reduced from baseline levels for all 3 treatment groups but not for the MMTP-only group. At the 26-week and 52-week follow-up points, CBT participants showed substantial improvement, resulting in equivalent performance with the CM groups as indicated by both urinalysis and self-reported cocaine use data. CONCLUSIONS: Study findings provide solid evidence of efficacy for CM and CBT. Although the effect of CM is significantly greater during treatment, CBT appears to produce comparable long-term outcomes. There was no evidence of an additive effect for the 2 treatments in the CM + CBT group.

Adult↗
PubMed2002

Buprenorphine: blending practice and research.

Although pharmacotherapy has been a mainstay in opiate addiction, not much research in the development of new opiate medications has been translated into clinical practice. In part, this is because opiate pharmacotherapy has not been an integral element of mainstream medical practice and because new medications developed by research are not available to clinicians. All that will change with the availability of buprenorphine for addiction treatment. For the first time in nearly a century, clinicians will be able to treat opiate addicts in the general medical setting, in the same manner they treat other patients. The unique pharmacological properties of buprenorphine, with its high patient acceptance, favorable safety profile, and ease of clinical administration, should facilitate its clinical integration. However, successful implementation will require changes in the understanding and attitude of clinicians, policymakers, and society.

Australia↗
PubMed2002

Smoking cessation in methadone maintenance.

AIMS: To evaluate relapse prevention (relapse prevention) and contingency management (contingency management) for optimizing smoking cessation outcomes using nicotine replacement therapy for methadone-maintained tobacco smokers. DESIGN: Experimental, 2 (relapse prevention)x2 (contingency management) repeated measures design using a platform of nicotine replacement therapy featuring a 2-week baseline period, followed by randomization to 12 weeks of treatment, and 6- and 12-month follow-up visits. SETTING: Three narcotic treatment centers in Los Angeles. PARTICIPANTS: One hundred and seventy-five participants who met all inclusion and no exclusion criteria. INTERVENTION: Participants received 12 weeks of nicotine replacement therapy and assignment to one of four conditions: patch-only, relapse prevention + patch, contingency management + patch and relapse prevention + contingency management + patch. MEASUREMENTS: Thrice weekly samples of breath (analyzed for carbon monoxide) and urine (analyzed for metabolites of opiates and cocaine) and weekly self-reported numbers of cigarettes smoked. FINDINGS: Participants (73.1%) completed 12 weeks of treatment. During treatment, those assigned to receive contingency management showed statistically higher rates of smoking abstinence than those not assigned to receive contingencies (F3,4680=6.3, P=0.0003), with no similar effect observed for relapse prevention. At follow-up evaluations, there were no significant differences between conditions. Participants provided more opiate and cocaine-free urines during weeks when they met criteria for smoking abstinence than during weeks when they did not meet these criteria (F1,2054=14.38, P=0.0002; F1,2419=16.52, P<0.0001). CONCLUSIONS: Contingency management optimized outcomes using nicotine replacement therapy for reducing cigarette smoking during treatment for opiate dependence, although long-term effects are not generally maintained. Findings document strong associations between reductions in cigarette smoking and reductions in illicit substance use during treatment.

Adolescent↗