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Studies the non-linear pharmacokinetics of methylenedioxymethamphetamine (MDMA or ecstacy) in humans in Great Britain. Pharmacological effects of the drug; Pharmacokinetic parameters for MDMA and methylenedioxyphetamine (MDA); Assessment of MDMA and MDA.

Long-term opioid consumption can induce hypoadrenalism through impairment of the hypothalamic-pituitary-adrenal axis. Results of the present study showed that, in heroin addicts, saliva cortisol concentrations varied according to the amount of recently consumed heroin and the time elapsed since the last self-administration. Hypercortisolism was observed either after abrupt withdrawal of heroin or the last dose of methadone. Post-detoxification hypercortisolism was still present on day 16 after the last opioid consumption, whereas it was not observed in abstinent addicts for a mean period of 4 months. During detoxification treatment, mean AUC[sub 8-24] cortisol in saliva of clonidine or guanfacine-treated patients was significantly higher than that in methadone-treated patients. It may be hypothesized that elevated cortisol levels may account for untoward effects of adrenergic agonist therapy which, in turn, may represent an added risk factor for relapse during detoxification. Further studies are necessary to correlate the severity of withdrawal symptoms to cortisol levels in opioid addicts detoxified with α[sub 2]-adrenergic agonist substitution. [ABSTRACT FROM AUTHOR]

In the early 80's opioid addiction was a low prevalence problem in Spain, grew enormously during that decade and became the most important risk factor for AIDS in recent years. The limitations of assessing the prevalence of illegal drug use by means of standard epidemiological methods lead, worldwide, to the use of indirect indicators. A Register of Toxicological Emergencies. developed for research purposes and containing data from 1979 to 1989 at the Hospital del Mar (Barcelona) is described. Results for opioid-related emergencies are presented, showing an epidemic increase in the number of such emergencies after 1981. The total number of opioid-related emergencies was 18042 with a mean of 2.23 opioid-related emergency admissions per client throughout the whole period, implying that some 8000 persons were seen. In episodes Prom non-arrestees, mean age increased slightly over time, the male/female ratio being 2.5; withdrawal was the more frequent reason for attendance (53%), overdoses accounting for 9% of admissions, and other medical conditions for 33%. Non-arrested women were more likely to attend for other medical conditions and overdoses than men. The importance of this kind of register as well as its limitations for assessing the trend of opioid use prevalence is discussed. [ABSTRACT FROM AUTHOR]

Naltrexone and placebo as adjuvant treatment of opioid dependence were compared in a double-blind, controlled clinical trial in 50 heroin addicts. The overall efficacy was assessed by the degree of treatment acceptance, percentage of relapse in heroin consumption, presence of side effects, and overall retention on naltrexone. A total of SO patients of both sexes, aged from 18 to 30years, who fulfilled DSM-III-R criteria for opioid dependence were included in the study. All patients completed detoxification with clonidine on an inpatient basis for 2 weeks and subsequently, on an out-patient basis, received oral naltrexone 050 mg per week) for a month. At the beginning of the second month patients were randomly allocated to treatment with nalirexone (28 patients) or placebo (22 patients) until a 6-month treatment period in a double-blind fashion had been completed. During the study period (1 year) all patients followed the same therapeutic schedule. Patients in both groups were comparable in terms of socio-demographic data and toxicological history. The efficacy of naltrexone was not superior to that of placebo as there were no significant differences in acceptance of treatment, retention rates, opioid and other drug consumption, drug compliance or side effects. [ABSTRACT FROM AUTHOR]

The pharmacokinetics and tolerance of repeated oral doses of furafylline were investigated in normal volunteers. In accord with predictions from single dose studies, steady state was achieved on the first day following the administration of 90 mg and maintained by subsequent daily doses of 30 mg. When corrected for body weight there were no significant differences in minimum and maximum plateau levels of furafylline between males (1.2-2.0 micrograms ml-1; mean body weight 67.2 kg) and females (1.6-2.6 micrograms ml-1; mean body weight 54.9 kg). The half-life of elimination was less when the plasma concentration was lower than 600 ng ml-1 than during the stationary phase of treatment. Despite constant plasma levels the repeated administration of furafylline appeared to be associated with the onset of adverse xanthine-like side effects, a finding which was subsequently traced to the presence of, and possible synergism with, accumulating serum levels of caffeine in those volunteers drinking caffeine containing beverages. Subsequent studies showed that a single dose (90 mg) of furafylline results in a rapid accumulation of caffeine given orally (100 mg twice daily) and that this is accompanied by an elimination half-life of some 50 h and an abrupt decrease in metabolite levels. The furafylline-induced accumulation of caffeine was not influenced by the smoking habits of the subjects, implying that the metabolite pathway blocked by furafylline is the demethylation of caffeine in position 3, an implication confirmed by the reduced formation of paraxanthine. This demonstration of an unacceptable level of adverse side effects resulting from a potent inhibiting effect of furafylline on the metabolism of a normal dietary constituent has obvious implications in the interpretation of drug-induced toxicity. [ABSTRACT FROM AUTHOR]