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1.
Clin Exp Pharmacol Physiol ; 30(10): 759-63, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14516415

ABSTRACT

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.


Subject(s)
Cold Temperature/adverse effects , Ketorolac/administration & dosage , Pain Threshold/drug effects , Pain/drug therapy , Sex Characteristics , Administration, Oral , Adult , Analysis of Variance , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Middle Aged , Pain/physiopathology , Pain Threshold/physiology
2.
J Clin Psychiatry ; 64(12): 1440-8, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14728105

ABSTRACT

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.


Subject(s)
Baclofen/therapeutic use , Cocaine-Related Disorders/rehabilitation , Cocaine/analogs & derivatives , GABA Agonists/therapeutic use , Adult , Baclofen/adverse effects , Cocaine/urine , Double-Blind Method , Female , GABA Agonists/adverse effects , Humans , Longitudinal Studies , Male , Middle Aged , Substance Abuse Detection , Treatment Outcome
3.
Drug Alcohol Depend ; 63(2): 139-46, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11376918

ABSTRACT

Patients on methadone maintenance therapy are relatively intolerant of pain, a finding hypothesized to reflect a hyperalgesic state induced by chronic opioid administration. To explore if the intrinsic activity of the opioid maintenance agent might affect expression of hyperalgesia in this population, withdrawal latency for cold-pressor (CP) pain was compared between small groups of methadone-maintained (n = 18), buprenorphine-maintained (n = 18), and matched control (n = 18) subjects. The opioid-maintained groups had equal and significantly shorter withdrawal latencies than controls, however it is possible that high rates of continued illicit opioid use precluded finding differences between methadone and buprenorphine groups. Differential effects of maintenance agent were found for the few subjects without illicit opioid use, such that withdrawal latencies for methadone-maintained (n = 5) were less than for buprenorphine-maintained (n = 7) which were less than controls (n = 18). Diminished pain tolerance in patients receiving opioid maintenance treatment has significant clinical implications. More research is needed to determine if buprenorphine offers advantages over methadone in this regard.


Subject(s)
Buprenorphine/therapeutic use , Methadone/therapeutic use , Opioid-Related Disorders/rehabilitation , Pain Threshold/drug effects , Adult , Buprenorphine/adverse effects , Cold Temperature , Female , Humans , Male , Methadone/adverse effects , Middle Aged , Opioid-Related Disorders/psychology , Reaction Time/drug effects
4.
J Pain Symptom Manage ; 20(4): 237-45, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11027904

ABSTRACT

Providing pain management for known opioid abusers is a challenging clinical task, in part because little is known about their pain experience and analgesic requirements. This study was designed to describe pain tolerance and analgesic response in a sample of opioid addicts stabilized in methadone-maintenance (MM) treatment (n = 60) in comparison to matched nondependent control subjects (n = 60). By using a placebo-controlled, two-way factorial design, tolerance to cold-pressor (CP) pain was examined, both before and after oral administration of therapeutic doses of common opioid (hydromorphone 2 mg) and nonsteroidal anti-inflammatory (ketorolac 10 mg) analgesic agents. Results showed that MM individuals were significantly less tolerant of CP pain than control subjects, replicating previous work. Analgesic effects were significant neither for medication nor group. These data indicate that MM opioid abusers represent a pain-intolerant subset of clinical patients. Their complaints of pain should be evaluated seriously and managed aggressively.


Subject(s)
Drug Interactions/physiology , Methadone/adverse effects , Opioid-Related Disorders/physiopathology , Pain/drug therapy , Adult , Cold Temperature/adverse effects , Female , Humans , Hydromorphone/administration & dosage , Hydromorphone/adverse effects , Ketorolac/administration & dosage , Ketorolac/adverse effects , Male , Middle Aged , Opioid-Related Disorders/drug therapy , Pain/physiopathology , Pain Measurement/statistics & numerical data , Pain Threshold/drug effects , Pain Threshold/physiology , Pressure/adverse effects , Reaction Time/drug effects , Reaction Time/physiology
5.
J Addict Dis ; 15(2): 85-92, 1996.
Article in English | MEDLINE | ID: mdl-8704003

ABSTRACT

Clinical trials designed to establish the effectiveness of a pharmacotherapy for the treatment of drug abuse typically call for the collection and analysis of three urine samples per week to detect changes in drug use patterns. Examination of over 16,500 urine samples collected from 225 subjects during a one year buprenorphine/methadone clinical trial indicates that analysis of one weekly urine sample from those collected on a three-times-per-week fixed schedule provides essentially the same outcome information as analysis of all three weekly urines. Further, the percent of opiate-positive samples is constant across weekday, indicating that a single urine, randomly selected from those collected each week, is a valid indicator of treatment performance.


Subject(s)
Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Methadone/therapeutic use , Narcotics , Substance-Related Disorders/rehabilitation , Substance-Related Disorders/urine , Adult , Female , Humans , Male , Middle Aged
6.
J Addict Dis ; 14(3): 97-114, 1995.
Article in English | MEDLINE | ID: mdl-8555282

ABSTRACT

The partial mu-opiate agonist, buprenorphine, is the subject of recent evaluation as a potential pharmacotherapy for cocaine dependence. This paper reviews the extant preclinical and clinical evidence of buprenorphine effectiveness in treating cocaine abuse, including data from our large methadone comparison trial and a smaller buprenorphine dose ranging study. Although buprenorphine appears to reduce cocaine self-administration in studies of non-opiate dependent animals, clinical evidence for the same response in opiate addicts abusing cocaine has not been demonstrated. Further efficacy trials should await preclinical demonstrations of effectiveness in samples with opiate and cocaine exposure.


Subject(s)
Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Cocaine , Substance-Related Disorders/rehabilitation , Analgesics, Opioid/administration & dosage , Buprenorphine/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Male , Methadone/administration & dosage , Methadone/therapeutic use
7.
Int J Addict ; 27(1): 15-23, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1537637

ABSTRACT

All patients admitted to a Residential Treatment Center (RTC), a drug-free hospital-based inpatient facility in February 1985 through July 1985, were followed-up 6 months after discharge. The results are contrasted with those obtained in 1973 in a similar follow-up study. Length of stay at RTC had been reduced from 1 year in 1973 to 3 months in 1985. Six months after discharge, the longer length of stay in 1973 appears to be almost twice as effective as the 3-month program in 1985.


Subject(s)
Length of Stay/statistics & numerical data , Residential Treatment/standards , Substance-Related Disorders/therapy , Adolescent , Adult , California/epidemiology , Follow-Up Studies , Health Services Research , Hospitals, Veterans , Humans , Male , Recurrence , Substance-Related Disorders/epidemiology , Time Factors , Treatment Outcome
8.
Addict Behav ; 14(3): 343-5, 1989.
Article in English | MEDLINE | ID: mdl-2750572

ABSTRACT

Two previous follow-ups of 50 patients at the Veterans Administration Medical Center, Brentwood Division, West Los Angeles, Residential Treatment Center (RTC), were conducted in 1974 and 1981. This is a 10-year follow-up of the same cohorts conducted in 1984. We were able to locate 11 out of 50 candidates. Of the 11 candidates located, interviews were completed on six candidates. Of the remaining five patients, two are decreased and the other three were unable to be interviewed. Of the six patients that were interviewed, three were drug-free since treatment; one has been drug-free for the last five years. The other two patients had been drug-free approximately six months. It would appear that follow-up studies of this particular group of subjects are very difficult and that the outcome of treatment is difficult to evaluate due to difficulty in locating this group of subjects over a long term.


Subject(s)
Substance-Related Disorders/rehabilitation , Therapeutic Community , Adult , Alcoholism/rehabilitation , California , Follow-Up Studies , Hospitals, Veterans , Humans , Male
9.
Addict Behav ; 10(3): 203-7, 1985.
Article in English | MEDLINE | ID: mdl-4083099

ABSTRACT

Most people would agree that a relationship exists between drinking alcohol and smoking cigarettes, but there is very little empirical evidence demonstrating a direct causal association. Study of the relationship has been hampered by the lack of a simple laboratory methodology. This article describes an efficient experimental paradigm. Fourteen male narcotic addicts in methadone maintenance treatment volunteered to come to the laboratory for two smoking sessions, during which each subject was given either an alcoholic drink or orange juice, followed by three cigarettes at 20-minute intervals. Drinking alcohol significantly increased the amount and rate of smoking. However, not all subjects reacted to alcohol with increased smoking, and we were unable to account for those individual differences. Our finding supports the theory that a direct causal mechanism linking smoking and drinking exists. That link probably has clinical significance, because there is evidence that ex-smokers are at particularly high risk when they drink alcohol.


Subject(s)
Alcohol Drinking , Opioid-Related Disorders , Smoking , Adult , Humans , Male , Middle Aged
10.
Int J Addict ; 19(1): 25-44, 1984 Feb.
Article in English | MEDLINE | ID: mdl-6706451

ABSTRACT

The results of analysis of successive relapse and remission times of many opiate addicts were examined. It is discovered that motivation is the preeminent factor that governs the distribution of lengths of remission times (periods of abstinence), differences in types of motivation leading to an underlying mixture of three or fewer Weibull distributions. On the other hand, two distinct factors-namely wear-out (dysfunction resulting from exhaustion or tiring out brought on by the addict's enforced life-style) and precipitation of events that may not be beyond the control of the addict-govern the distribution of lengths of relapse times (periods of using opiates), leading, typically, to an underlying competing-risk distribution. Methods for using this information to aid in treatment and in research are described.


Subject(s)
Narcotics , Substance-Related Disorders/psychology , Temperance , Humans , Inactivation, Metabolic , Male , Models, Psychological , Motivation , Narcotics/metabolism , Random Allocation , Substance-Related Disorders/rehabilitation , Time Factors
11.
Arch Gen Psychiatry ; 40(8): 851-4, 1983 Aug.
Article in English | MEDLINE | ID: mdl-6347118

ABSTRACT

A multicentered clinical trial studied the efficacy and safety of disulfiram in controlling heavy alcohol consumption by patients on methadone maintenance regimens. The trial was stopped when sample size targets were not achieved. Efficacy comparisons were based on 82 patients who started the study; safety comparisons were based on 35 patients who completed 12 weeks of study. Patients received either disulfiram and methadone or placebo and methadone. Disulfiram was administered at a dosage of 125 mg/day for seven days and 250 mg/day thereafter for 36 weeks. No significant differences between the disulfiram and placebo groups were observed in either the retention in study or any other important end point. Both groups showed improvement in control of drinking during the study. There were no serious adverse reactions that could be attributed to the combined use of the two drugs.


Subject(s)
Alcoholism/rehabilitation , Disulfiram/therapeutic use , Methadone/therapeutic use , Adult , Alcohol Drinking , Alcoholism/complications , Alcoholism/psychology , Clinical Trials as Topic , Double-Blind Method , Drug Therapy, Combination , Humans , Opioid-Related Disorders/complications , Opioid-Related Disorders/rehabilitation , Placebos , Random Allocation
12.
Drug Alcohol Depend ; 6(5): 273-84, 1980 Nov.
Article in English | MEDLINE | ID: mdl-7460760

ABSTRACT

Fifty of sixty original study subjects were assessed via two questionnaires and urinalysis tests between six months and one year following completion of the experimental program. Results indicate a high rate of retention in methadone/methadyl acetate treatment, and point to the need for positive social context, satisfactory interpersonal relationships, and good role functioning as concomitants to achieving drug-free status.


Subject(s)
Heroin Dependence/rehabilitation , Methadone/analogs & derivatives , Methadone/therapeutic use , Methadyl Acetate/therapeutic use , Alcohol Drinking , California , Double-Blind Method , Employment , Follow-Up Studies , Humans , Interpersonal Relations , Methadone/urine , Social Adjustment
13.
Drug Alcohol Depend ; 6(5): 345-8, 1980 Nov.
Article in English | MEDLINE | ID: mdl-7460765

ABSTRACT

Immunoglobulin levels of 21 heroin addicts at the Brentwood Veterans Administration Hospital Drug Treatment Service were studied after 9 months of treatment with methadone or methadyl acetate. This paper discusses the results of this study regarding IgM, IgA, and IgG levels.


Subject(s)
Heroin Dependence/immunology , Immunoglobulins/analysis , Methadone/analogs & derivatives , Methadone/therapeutic use , Methadyl Acetate/therapeutic use , Adult , Heroin Dependence/rehabilitation , Humans , Middle Aged
14.
Drug Alcohol Depend ; 6(3): 137-9, 1980 Sep.
Article in English | MEDLINE | ID: mdl-7000479

ABSTRACT

In a previous article the authors reported renal transplantation in a male veteran heroin addict being treated with methadone maintenance. They now report the 5-year follow-up of this patient and his subsequent renal transplant rejection.


Subject(s)
Heroin Dependence/complications , Kidney Failure, Chronic/etiology , Methadone/therapeutic use , Adult , Follow-Up Studies , Graft Rejection , Heroin Dependence/rehabilitation , Humans , Kidney Failure, Chronic/therapy , Kidney Transplantation , Male , Transplantation, Homologous
15.
Arch Gen Psychiatry ; 35(8): 989-91, 1978 Aug.
Article in English | MEDLINE | ID: mdl-678048

ABSTRACT

Chromosomes of peripheral leukocytes were examined in 28 addicts participating in a Veterans Administration-Special Action Office for Drug Abuse Prevention (SAODAP) cooperative study of methadyl acetate vs methadone. Blood samples for 72-hour leukocyte cultures were drawn after nearly 40 weeks of maintenance therapy while subjects were receiving active medication. For comparison, ten nondrug users were also studied. The frequency of chromosome damage was not greater in subjects maintained on methadyl acetate or methadone than in nondrug users.


Subject(s)
Chromosome Aberrations , Methadone/analogs & derivatives , Methadone/adverse effects , Methadyl Acetate/adverse effects , Adult , Double-Blind Method , Heroin Dependence/rehabilitation , Humans , Leukocytes/ultrastructure , Male , Methadone/administration & dosage , Methadyl Acetate/administration & dosage , Middle Aged , Time Factors
16.
Am J Drug Alcohol Abuse ; 5(4): 415-23, 1978.
Article in English | MEDLINE | ID: mdl-755381

ABSTRACT

The level of heroin craving was monitored in patiens receiving naltrexone on a regular basis. Meetings and interviews conducted twice weekly attested to a pattern of craving reduction in most but not all the addicts. It was also found that it usually took 3 to 5 weeks for this effect to occur. The possible relationship between drug craving and participation in the naltrexone program is discussed.


Subject(s)
Heroin Dependence/psychology , Naloxone/analogs & derivatives , Naltrexone/therapeutic use , Heroin Dependence/rehabilitation , Humans , Patient Dropouts
18.
Med J Aust ; 2(13): 433-4, 1977 Sep 24.
Article in English | MEDLINE | ID: mdl-600139

ABSTRACT

A 30-year-old veteran heroin addict being treated with methadone maintenance suffered renal failure. He underwent haemodialysis, peritoneal dialysis and cadaveric renal transplantation while being maintained on methodone. This report illustrates long-term treatment of heroin addicts with renal failure.


Subject(s)
Heroin Dependence/rehabilitation , Kidney Failure, Chronic/therapy , Methadone/therapeutic use , Adult , Heroin Dependence/complications , Humans , Kidney Failure, Chronic/etiology , Male
19.
Med J Aust ; 2(5): 150-2, 1977 Jul 30.
Article in English | MEDLINE | ID: mdl-331052

ABSTRACT

Sixty subjects participated in a double-blind study comparing methadyl acetate (80 mg) with two dosages of methadone (50 mg and 100 mg) in the maintenance of opiate addicts. The safety of all three regimens was supported and methadyl acetate was as effective as methadone in the retention of subjects.


Subject(s)
Heroin Dependence/rehabilitation , Methadone/therapeutic use , Adult , Clinical Trials as Topic , Heroin Dependence/urine , Humans , Illicit Drugs/urine , Male , Methadone/administration & dosage , Methadyl Acetate/therapeutic use , Morphine/urine , Patient Dropouts
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