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not in the initial exposures. Given to a postoperative patient these analgesics provide a welcome relief of pain, but addiction from such medical use is uncommon. When given to an average pain-free subject, morphine produces nausea and sedation, but rarely euphoria. What, then, is the temptation to become an addict? So far as can be judged from the histories of addicts, many of them found the first trials of a narcotic in some sense pleasurable or tranquilizing, even though the drug also caused nausea and vomiting. Perhaps their reaction to the drug was abnormal, even on the first exposure. However this may be, with repeated use and development of tolerance to side effects, the euphoric action evolved and the subjects became established addicts.

Drug-seeking behavior, like theft, is observed after addiction is established and the narcotic drug has become euphorigenic. The question as to whether this abnormality in reaction stems from a basic weakness of character or is a consequence of drug usage is best studied when drug hunger is relieved. Patients on the methadone maintenance program, blockaded against the euphorigenic action of heroin, turn their energies to school work and jobs. lt would be easy for them to become passive, to live indefinitely on public support and claim that they had done enough in winning the fight against heroin. Why they do not yield to this temptation is unclear, but in general they do not. Their struggles to become self-supporting members of the community should impress the critics who had considered them self-indulgent when drug-hungry addicts. When drug hunger is blocked without production of narcotic effects, the drug-seeking behavior ends.

So far as can be judged from retrospective data, narcotic drugs have been quite freely available in some areas of New York City, and experimentation by adolescents is common. The psychological and metabolic theories diverge somewhat in interpreting this fact; the first postulates preexisting emotional problems and a need to seek drugs for escape from reality, whereas the alternative is that trial of drugs, like smoking the first cigarette, may be a result of a normal adolescent curiosity and not of psychopathology (Wikler and Rasor 1953). As to the most important point—the reasons for continuation of drug use in some cases and not in others—there is no definitive information, either psychological or metabolic. This is obviously a crucial gap in knowledge. Systematic study of young adolescents in areas with high addiction rates is needed to define the process of becoming addicted and to open the way for prevention.

The other extreme—the cured addict—involves a controversy as to the goal of therapy. Those of us who are primarily concerned with the social productivity of our patients define success in terms of behavior— the ability of the patients to live as normal citizens in the community— whereas other groups seek total abstinence, even if it means confinement of the subjects to an institution. This confusion of goals has barred effective comparison of treatment results.

Actually, the questions to be answered are straightforward and of great practical importance. Do the abstinent patients in the psychological programs have a residual metabolic defect that requires continued group pressure and institutionalization to enforce the abstinence? Conversely, do the patients who are blockaded with methadone exhibit any residual psychopathology? No evidence is available to answer the first question. As to the latter point, we can state that the evidence so far is negative. The attitudes, moods, and intellectual and social

performance of patients are under continuous observation by a team of psychiatrists, internists, nurses, counselors, social workers, and psychologists. No consistent psychopathology has been noted by these observers or by the social agencies to which we have referred patients for vocational placement. The good records of employment and school work further document the patients' capacity to win acceptance as normal citizens in the community.

The real revolution of the methadone era was its emphasis on rehabilitation rather than on detoxification. This reversed the traditional approach to addiction, which had been based on the assumption that abstinence must come first. According to the old theory, rehabilitation is impossible while a person is taking drugs of any kind, including methadone. The success of methadone programs in rehabilitating addicts who had already failed in abstinence programs decisively refuted this old theory. lndeed, nowhere in the history of treatment has a program with the abstinence approach achieved even a fraction of the retention rate and social rehabilitation now seen in the average methadone clinic. This statement includes all of the abstinence-oriented programs of governmental institutions, therapeutic communities, and religious groups for which any data are available (Brecher 1972; Glasscote 1972).

We believe that it is a serious mistake for programs to put a higher value on abstinence than on the patient's ability to function as a normal member of society. After the patient has arrived at a stable way of life with a job, a home, a position of respect in his community, and a sense of worth, it may, or may not, be best to discontinue methadone, but at least he can consider this option without pressure. The pharmacologic symptoms of withdrawal will be the same whether or not the addict is socially rehabilitated, but with a job and family there is much more to lose if relapse occurs, and therefore the motivation to resist a return to heroin will be strong. The time spent in maintenance treatment does not make detoxification more difficult. lt has proved very easy to withdraw methadone from patients who have been maintained for one to eight years when the reduction in dose has been gradual and the patient free from anxiety.

As with heroin, the real problems begin after withdrawal. The secondary abstinence syndrome, first described by Himmelsbach, Martin, Wikler, and colleagues at the United States Public Health Hospital, Lexington, Kentucky, in patients detoxified from morphine and heroin, reflects the persistence of metabolic and autonomic disturbances in the postnarcotic withdrawal period (Himmelsbach 1942; Martin et al. 1963; Martin and Jasinski 1969): These persistent abnormalities in metabolism are clearly pharmacologic since they occur also in experimental animals addicted to narcotics and then detoxified. Followup studies of abstinent ex-addicts have emphasized the frequency of alcoholism and functional deterioration (Brecher 1972).

An unfortunate consequence of the early enthusiasm for methadone treatment is today's general disenchantment with chemotherapy for addicts. What was not anticipated at the onset was the nearly universal reaction against the concept of substituting one drug for another, even when the second drug enabled the addict to function normally. Statistics showing improved health and social rehabilitation of the patients receiving methadone failed to meet this fundamental objection. The analogous long-term use of other medications such as insulin and digitalis in medical practice has not been considered relevant.

Perhaps the limitations of medical treatment for complex medical-social problems were not sufficiently stressed. No medicine can rehabilitate persons. Methadone maintenance makes possible a first step toward social rehabilitation by stabilizing the pharmacological condition of addicts who have been living as criminals on the fringe of society. But to succeed in bringing disadvantaged addicts to a productive way of life, a treatment program must enable its patients to feel pride and hope and to accept responsibility. This is often not achieved in present-day treatment programs. Without mutual respect, an adversary relationship develops between patients and staff, reinforced by arbitrary rules and the indifference of persons in authority. Patients held in contempt by the staff continue to act like addicts, and the overcrowded facility becomes a public nuisance. Understandably, methadone maintenance programs today have little appeal to the communities or to the majority of heroin addicts on the street.

Methadone maintenance, as part of a supportive program, facilitates social rehabilitation, but methadone treatment clearly does not prevent opiate abuse after it is discontinued, nor does social rehabilitation guarantee freedom from relapse.

For the previously intractable heroin addict with a pretreatment history of several years of addiction and social problems, the most conservative course, in our opinion, is to emphasize social rehabilitation and encourage continued maintenance. On the other hand, for patients with shorter histories of heroin use, especially the young ones, a trial of withdrawal with a systematic followup is indicated when physician and patient feel ready for the test, and when they understand the potential problems after detoxification. The first step of withdrawing methadone is relatively easy and can be achieved with a variety of schedules, none of which have been shown to have any specific effect on the long-range outcome. The real issue is how well the patient does in the years after termination of maintenance.

A Chronobiological
Control Theory

Mark Hochhauser, Ph.D.

CHRONOBIOLOGICAL VARIABLES

The effects of a given drug are a function of a number of variables; some of these variables, such as dosage level, have been considered as representing a specific chemical effect, unique to the amount of the drug ingested by the individual. Other variables, such as psychological set, are considered to be nonspecific, and may be viewed as an individualized behavioral process, insofar as each drug user will have his or her own idiosyncratic psychological response to a given drug.

Chronobiology (Halberg et al. 1977) offers a possible synthesis of these chemical and behavioral variables. Briefly stated, chronobiology (or biological rhythms) concerns the temporal aspects of biology; numerous experiments have shown that both animal and human behavior vary as a function of such rhythms (Luce 1971; von Mayersbach 1967) and that drug effects may be particularly sensitive to changes in such chronobiological rhythms.

A number of chronobiological rhythms have been identified: circadian (about 24 hours), diurnal/nocturnal (variations in light and dark periods), ultradian (less than 24 hours), monthly, or even yearly. Unfortunately, the role of such rhythms in human behavior has often been grossly misrepresented (e.g., McConnell 1978).

An understanding of chronobiological rhythms and how they affect (and are affected by) behavior is essential to a more complete understanding of subject-drug interactions. Unfortunately, very little is known about the field of developmental chronobiology (Petren and Sollberger 1967), although it has been documented that drugs will exert differential effects, depending upon the level of physiological and psychological maturity achieved by the subject (Young 1967; Vessel 1968; Vernadakis and Weiner 1974; Conroy and Mills 1970; Yaffee et al. 1968).

CHRONOBIOLOGY AND DRUGS

There has been some empirical and theoretical work done on the relationship between chronobiology and drug effects (Nair 1974; Reinberg 1973; Reinberg and Halberg 1971); however, such findings have not been extrapolated to problems of drug addiction. The following is a brief summary of the relationship between drugs and chronobiological variables.

AMPHETAMlNES

Rats have demonstrated circadian variation in their susceptibility to d-amphetamine sulfate (Scheving 1969); furthermore, diurnal variations (i.e., differences in responsivity between periods of light and dark) have also been found for methamphetamine and p-chloromethamphetamine (Evans et al. 1973).

BARBlTURATES

Rats have also demonstrated long-term variation (i.e., seasonal effects) in their responsivity to barbiturates (Beuthin and Bosquet 1970), as well as daily variations (Davis 1962). Such temporal effects have been attributed to changes in the rate of barbiturate metabolism by enzymes in the liver (Radzialowski and Bosquet 1968). Further, daily variations have been observed with phenobarbital (Pauly and Scheving 1964), and different doses of pentobarbital have had different effects as a function of circadian rhythms (Nelson and Halberg 1973). Moreover, there are apparent chronobiological differences even within the barbiturate category, as some barbiturates (e.g., phenobarbital) are long lasting, while others (e.g., hexobarbital) act for a shorter period of time (Muller 1974). Finally, it has been noted that the duration of barbiturate-induced sleep in rats was a function of the circadian phase of administration; the same barbiturate, administered in the same dose but at different times, produced variable levels of sleep. These findings suggested that the neurotransmitters that control sleep may display rhythmic levels of activity (Friedman 1974).

ALCOHOL

Alcohol studies on humans have found that ethanol is metabolized faster in the evening than in the afternoon, at least among some alcoholics (Jones and Paredes 1974). However, on cognitive tasks, Jones (1974) has found that alcohol impaired cognitive performance more in the afternoon than in the evening, suggesting a faster metabolic rate for alcohol in the afternoon. Studies with mice have also demonstrated dramatic variations in alcohol susceptibility over a 24-hour period; depending upon the time of administration, the mortality rate could be increased fivefold (Haus and Halberg 1959). More recently, Zeiner and Paredes (1978) have obtained racial differences in the circadian variation of ethanol metabolism; they found that a higher peak blood alcohol concentration was reached in the morning than in the afternoon among white male subjects, while for a male Native American group the peak blood alcohol concentration was lowest in the morning and highest at night.

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