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The physiology of drug addiction is reviewed. Topics include factors influencing drug abuse, drug effects and mechanisms of action, neurobiology, and neuroadaptation to long-term drug use. Drug abuse can cause structural changes in the brain, which makes long-term treatment so challenging.

In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient defoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone-associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms. Keywords--opiate withdrawal; methadone; guanfacine; heroin addiction; treatment-efficacy.

The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n=11) or placebo (n=11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic. [ABSTRACT FROM AUTHOR]

The behavioral effects of a drug are related to three factors: its intrinsic pharmacological activity, its physicochemical properties, and its pharmacokinetic parameters. In many cases differences in absorption, distribution, metabolism, and elimination may explain the different abuse liability profiles of drugs from within the same pharmacological class. Rapid absorption rate and high lipid solubility are the most important factors contributing to early drug concentrations in the brain. Differences in drug metabolism may be related to dose-dependent kinetics, first-pass metabolism, and variations in genetic traits (e.g. poor or extensive metabolizers). Metabolic pathways may produce active metabolites with similar or greater pharmacological activity than the parent substance. Drugs with a rapid elimination rate have been associated with greater self-administration and with early emergence of withdrawal symptoms. More pharmacokinetic studies are needed in human drug abuse liability evaluations. Knowledge of the plasma concentrations of drugs and their pharmacokinetic parameters can be essential to interpret differences among similar drugs in human abuse liability assessments. [ABSTRACT FROM AUTHOR]

The efficacy of clonidine, methadone, and guanfacine in rapid detoxification of heroin inpatients was assessed in a randomized controlled clinical trial. Signs and symptoms of abstinence and of side effects were analysed in 90 heroin addicts successfully completing a 12-day inpatient trial, all patients fit DSM-III criteria for opioid dependence, the age range being 18 to 36 years. All three drugs were effective in controlling abstinence; however, the course of abstinence was different in the methadone group as compared to the adrenergic agonists, the latter showing limitations in their ability to suppress withdrawal manifestations. While mean number of withdrawal signs and symptoms was significantly lower during days 2 to 5 in the methadone group (p.<0.01), adrenergic agonists were slightly more effective at the end of the trial. Incidence of side effects was closely related to the dose administered. Hypotensive action of adrenergic agonists was more marked in orthostatic position. The present results suggest that methadone is superior to adrenergic agonists. Between these drugs clonidine appears to be less effective than guanfacine in controlling some withdrawal manifestations, and causes more side effects, mainly of cardiovascular nature. [ABSTRACT FROM AUTHOR]

Predictors of either detoxification success or failure were evaluated during an inpatient trial that compared the efficacy of methadone, clonidine and guanfacine for rapid heroin detoxification. The analysis of such predictors was stimulated by the fact that in order to achieve 90 patients who completed the study (30 in each group), a total of 170 patients had to be included. Of 80 detoxification failures, 10 occurred in the methadone group, 32 in the guanfacine group, and 38 in the clonidine group. Voluntary request for discontinuation of the detoxification schedule was the first cause of failure. There were not statistically significant differences with regard to sociodemographic characteristics and pattern of drug consumption among patients in the three groups who completed detoxification with success or failure. The treatment drug, the type of schedule and the score obtained from the Symptom Checklist-90/Revised (SCL-90/R) were the only predictors of either detoxification success or failure. Inpatient opioid detoxification would be a useful strategy for patients with more severe psychological symptoms. [ABSTRACT FROM AUTHOR]

The EMETYST (Estudio Multicentrico de Evaluacion de Tratamientos y Seguimiento de Toxicomanos) project describes demographic characteristics and history of drug abuse in a sample of 311 heroin addicts, who began treatment for addiction between the months of March and July 1985 in 16 different outpatient drug-free clinics in Spain. The outcome of these patients was studied prospectively at 6 and 12 months after the onset of treatment. Drug use, psychological status, occupational status, and legal status were the main areas of interest. At 12 months, 51% of patients had discontinued heroin use (p<0.01). Ten per cent of patients remained on treatment for 1 year of more. As previously reported in other studies, treatment decreased heroin use and improved psychological status. Predictive factors of the patient's status at 12 months were duration of therapy, pretreatment criminal history, and results obtained at 6-month follow-up. [ABSTRACT FROM AUTHOR]