PubMed HealthSearch

Biomedical subjects

S M Mirin

Publications and source records attributed to S M Mirin.

13 recordsLinked to original sources

Opiates, catecholamines, behavior, and mood.

Indirect evidence has linked opioid reinforcement with changes in noradrenergic metabolism secondary to drug administration. Methodological precedents for biobehavioral correlations in depressive illness have suggested an important association between changes in mood and biogenic amine excretion patterns in the urines of patients during depression and recovery. This paper presents preliminary data on the possible relationship between changes in catecholamine excretion that were observed and the changes in behavior, mood, psychiatric status, and cardiorespiratory physiology secondary to heroin administration and methadone-assisted withdrawal. This study focuses on the urinary excretion of MHPG, since an appreciable fraction of this metabolite is probably derived from norepinephrine originating in the brain. The subjective changes in mood associated with heroin use, the decrease in respiratory rate, and the behavioral and mental status effects associated with opiate intoxication were observed only in the individuals whose MHPG excretion increased during the period of opiate administration.

Adult

Catecholamine metabolism during heroin use.

The authors examined urinary levels of catecholamines and metabolites during a 10-day period of heroin use in 9 subjects. Catecholamine and metabolite excretion increased over baseline values on the first day of heroin use, but markedly different patterns of change emerged later. In contrast to the significant increase in normetanephrine and decrease in metanephrine excretion in all 9 subjects during heroin use, only 4 subjects showed an increase in 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion. Moreover, it appeared that the increase in MHPG excretion in this subgroup began on the day before heroin administration, which suggests the possibility of an anticipatory or conditioned response.

Catecholamines

A behavioral paradigm for the evaluation of narcotic antagonists.

We have developed an experimental paradigm for the behavioral evaluation of narcotic antagonists. The study specifically examined the heroin-seeking behavior of hard-core narcotic addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. A long-term follow-up program in the community, with aftercare services, was utilized to determine the relationship between behavior observed on the research ward and behavior that occurred in the community. While preliminary one-month follow-up data offered some cause for an optimistic view of narcotic antagonist treatment, behavioral data observed on the research ward raised serious doubts about the possibility of extinguishing heroin self-administration with antagonists. The behavioral data were not consistent with laboratory descriptions of extinction. Rather, the data suggested that narcotic antagonist programs should emphasize the development of contingencies for the reinforcement of narcotic antagonist self-administration to ensure an opiate-free state, instead of focusing on an extinction approach.

Adult

Psychopathology and mood during heroin use: acute vs chronic effects.

In the context of evaluating the effects of a narcotic antagonist on opiate acquisition, 14 detoxified addicts self-administered increasing doses of unblocked heroin intravenously over a ten-day period. Early in the addiction cycle, subjects experienced tension relief and euphoria but this was followed shortly by a shift in the direction of increasing dysphoria and psychopathology. Nonetheless, individual injections of the drug continued to induce brief episodes of positive mood, an effect enhanced by frequent injection. Heroin self-administration was sharply reduced when subjects were blocked with naltrexone, a narcotic antagonist, and the negative effects observed during unblocked drug use were not observed.

Acute Disease

Analysis and modification of opiate reinforcement.

The authors describe a research protocol for the evaluation of narcotic antagonists which examines the heroin-seeking behavior of hard-core heroin addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. This paper serves as an introduction to a series of papers which follow dealing with behavioral, psychiatric, and aftercare results. It describes detailed methods and preliminary results for the first 21 subjects admitted to the study. More specific results are reported in the papers that follow.

Adult

Opiate antagonists and the modification of heroin self-administration behavior in man: an experimental study.

The heroin self-administration behavior of 8 inpatient heroin addicts was examined for 10 days under blocked (i.e., following ingestion of narcotic antagonists--naloxone or naltrexone) and unblocked (no antagonist) conditions. In the unblocked state, subjects injected all the available heroin, but they ceased heroin use almost completely following antagonist administration. Possible explanations for these results are discussed along with their implications for treatment.

Adult

Psychopathology, craving, and mood during heroin acquisition: an experimental study.

Six detoxified addict volunteers were allowed to self-administer intravenous heroin on an essentially self-determined schedule. Two periods of heroin acquisition were compared: an unmodified cycle in which patients could become intoxicated and a later cycle in which the effects of heroin were blocked with a narcotic antagonist. In the unblocked condition, patients initially experienced an increase in positive mood, but with chronic administration there was a significant rise in psychopathology and the development of a generalized dysphoric state. Similar changes did not occur when the same patients took heroin while blocked with a narcotic antagonist. Drug craving rose dramatically when "unblocked" heroin was available, but gradually fell during methadone detoxification. Following treatment with a narcotic antagonist, the presence of heroin failed to elicit any sustained rise in craving and drug taking was dramatically reduced.

Adult

Effects of heroin and methadone on plasma cortisol and testosterone.

Narcotic addicts self-administered heroin intravenously for 10 days under controlled research ward conditions and were subsequently detoxified with methadone for 7 days. Plasma testosterone levels decreased signifcantly when heroin dosage was between 45 and 65 mg/day contrasted to predrug base-line levels. Testosterone levels remained depressed during methadone withdrawal. No statistically significant changes in a.m. plasma cortisol levels were observed during both heroin acquisition and methadone withdrawal.

Adult