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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.

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.

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.

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 highs 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.

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.