The Theoretical Basis of Narcotic Addiction Treatment with Narcotic Antagonists

The theoretical basis of narcotic addiction treatment with narcotic antagonists was well stated by Martin et al. (). Briefly, outpatient maintenance of a previously detoxified opioid addict on a daily oral opioid-blocking dose of a narcotic antagonist is expected to accomplish two objectives: (a) to remove the incentive for seeking and using opioid drugs; and (b), to extinguish conditioned abstinence (including “craving”) should this phenomenon occur as a response to environmental stimuli to which unconditioned abstinence had previously become conditioned (). Needless to add, such a period of out-patient maintenance on a narcotic antagonist should be used to “rehabilitate” the patient – i.e., to train him in the skills necessary for holding a socially useful job. to form new, mutually supportive relationships with non-drug using persons, and to persuade him to give up the illegal “hustling” activities which had become self-reinforcing during previous periods of opioid addiction. Such a period of out-patient maintenance on a narcotic antagonist would have advantages over detoxification followed by enforced abstention from opioids (by prison sentences with or without a subsequent probationary period) in Read more […]

Human Dependence on Tobacco and Opioids: Common Factors

Recent years have seen increasing acceptance of the notion that tobacco is an addictive or dependence-producing substance, particularly as it is used in cigarette smoking. This idea is supported by the observations that tobacco serves as a reinforcer (i.e., it maintains behavior leading to its use) and that most people who smoke cigarettes would like to quit but cannot, even in the face of well documented health risks and economic sacrifices (Surgeon General’s Report 1979). The term “drug dependence” suggests that (1) the drug serves as a reinforcer, (2) behavior occurs which is maintained by the opportunity to take the drug, and/or (3) other reinforcers are sacrificed as a consequence of taking the drug (). Many cigarette smokers in some degree satisfy these criteria for drug dependence (). Since cigarette smoking has only recently been conceptualized as an instance of drug dependence, it should be useful to systematically compare cigarette smoking with another more thoroughly studied dependence process such as opioid dependence or narcotic addiction. At first blush, cigarette smoke and opioid drugs appear to produce vastly differing pharmacological and behavioral effects: large doses of opioids can produce Read more […]

Drug effects on behavior maintained by food, electric-shock presentation and stimulus-shock termination

Although early experiments did not find differences in drug effects depending on the type of event, more recent studies have reported several instances in which the maintaining event appeared to influence the effects of several drugs on behavior. For example, morphine, methadone, and the narcotic antagonists naloxone and nalorphine decreased responding maintained under 5-minute fixed-interval food-presentation schedules at doses that increased responding comparably maintained by the presentation of an electric shock (). Under similar schedule conditions, both amphetamine () and cocaine () increased responding maintained by these two events. However, appropriate doses of pentobarbital, ethanol, and chlordiazepoxide increased responding maintained by food, while only decreasing responding under shock-presentation schedules (). These findings suggested that there were several conditions under which certain drugs appeared to affect similar performances maintained under comparable schedules in an event-dependent manner. Further, as shown in Figure Effects of chlordiazepoxide on different control rates of responding under S-minute fixed-interval schedules of food or shock presentation. The event pen was defected downward Read more […]

Studies of Acute Alcohol Effects in Women and Animal Models

Alcohol Effects on Basal Hormone Levels Another approach to examination of alcohol’s toxic effects on reproductive function is to administer a single acute dose of alcohol to a normal healthy woman or experimental animal and measure the effects on pituitary and ovarian steroid hormones. Through a systematic manipulation of alcohol dose and changes in hormone levels, it should be possible to establish whether alcohol primarily disrupts hypothalamic, pituitary, or ovarian function. Surprisingly, studies of acute alcohol administration have shown that alcohol has minimal effects on basal hormone levels. Alcohol did not significantly suppress LH or estradiol in normal women or in female macaque monkeys. These data suggest that a single episode of intoxication is probably not sufficient to suppress normal basal hormone levels and that repeated episodes of intoxication are required to produce the hormonal correlates of amenorrhea, anovulation, and luteal phase dysfunction observed in clinical studies. One procedural difficulty affecting all investigations of acute alcohol effects on basal hormone levels is that studies have usually been conducted during the early follicular or luteal phase of the menstrual cycle, when basal Read more […]

Internal Stimulus Control and Subjective Effects of Drugs

For many years psychotropic drugs have been characterized and classified using methods designed to measure their subjective effects in humans (). This research approach has two principal purposes: 1) to investigate the efficacy of a drug in attenuating unwanted subjective states in patients (e.g., pain, anxiety, depression), 2) to investigate the abuse potential of new drugs by comparing their subjective effects in experienced drug abusers to those produced by known drugs of abuse. In regard to the latter, such methods have been used to determine whether there are any common subjective states produced by all drugs of abuse (e.g., euphoria). Systematic studies of subjective methods for drug classification have been conducted at the Addiction Research Center (ARC) in Lexington, Kentucky, now part of the National Institute on Drug Abuse. A major mission of the ARC has been to evaluate new analgesic compounds to determine whether they produced morphine-like effects. The subjective effects of morphine and related compounds were an important aspect of this evaluation. The research demonstrated that morphine and related narcotic analgesics produced a unique spectrum of subjective effects that can be reliably discriminated Read more […]

Classically Conditioned Phenomena in Human Opiate Addiction

Classical and operant conditioning factors are both potentially significant in the maintenance of opiate use. Analysis from the perspective of the operant conditioning paradigm emphasizes the importance of discriminative stimulus control and the efficacy of opiates as reinforcers (). In the context of the classical conditioning paradigm, emphasis is placed on environmental correlates of drug effects and withdrawal symptoms as elicitors of overt behavioral and physiological responses. Concurrently it must be recognized that a model based on integration of both paradigms probably reflects most accurately the reality of human opiate dependence (). In the context of either the operant or classical conditioning paradigms, seemingly contradictory and diverse effects of stimuli and events may be identified. However, careful analysis leads to the conclusion that systematic results prevail and that findings parallel those involving other behaviors and reinforcers. As has been discussed in a recent review (), the primary problems appear to arise in delineating the phase of opiate action (e.g., onset, termination, withdrawal) with which stimulus events are associated. A secondary problem arises in differentiating patterns of Read more […]

History of Drug Exposure as a Determinant of Drug Self-Administration

The purpose of this paper is to review how a drug’s effectiveness in initiating and maintaining self-administration can be influenced by a subject’s past experience with drugs. Drug self-administration by humans and laboratory animals is considered an instance of operant behavior (), controlled by the subject’s genetic constitution, past history, and the current circumstances of drug availability (of Skinner, 1938). The influence of history of drug exposure on current drug-maintained behavior may be controlled, in turn, by the particular drugs and doses employed and the conditions under which the drug is administered. This discussion will focus on the ways in which a history of drug exposure can control later drug self-administration in laboratory animals. Effects of history of drug exposure on initiation of drug self-administration In order to study drug self-administration by laboratory animals, an experimenter must set up a situation in which subjects are exposed to some contingency between the occurrence of a specific response and delivery of a particular drug. For many drugs, no explicit behavioral or pharmacologioal history is necessary for the drug to maintain behavior. In one initial study, for example, Read more […]

The development of sustained action preparations of narcotic antagonists

The use of narcotic antagonists in the treatment of opiate addiction is based on the concept of a pharmaceutical agent capable of blocking the reinforcing properties of a dose of opiate taken during an addicts rehabilitation. The rationale for use is that the antagonist blocks the opiate “high” and makes it pleasureless, thus removing the addict’s incentive for continued use. Earlier successful therapy with cyclazocine and naloxone prompted the full-scale development of new and superior antagonists. Presently naltrexone is the drug under the most intensive clinical evaluation and appears to be a promising antagonist candidate. It was felt from the outset that a most desirable component of antagonist therapy would be long-acting drug, so that the need for an addict to decide to take his medication would be minimized. Naltrexone in oral doses of 70 mg. will provide adequate blocking protection for at least 48 hours, or perhaps 72 hours in certain individuals. This is not felt to be a long enough interval between dosages to aid the addict in becoming dissociated from his drug-taking behavior. It was recognized very early that in order to achieve the desired one week, one month or longer duration between dosages, Read more […]

Nida’s Naltrexone Research Program

The current naltrexone research program sup ported by the National Institute on Drug Abuse can be traced developmentally to its embryonic beginnings in the mid-1960’s. At that time Dr. William Martin and his co-workers at the Addiction Research Center in Lexington, Kentucky initiated a series of studies into the use of narcotic antagonists for the treatment of opioid dependence (). The studies were a practical outgrowth of the theoretical formulations elaborated by Dr. Abraham Wikler over the preceding years (). The results of the studies showed that a narcotic antagonist could be effectively used to block the euphorigenic and dependence-producing properties of opioids in man. Furthermore, this chemotherapeutic agent would produce neither physical dependence nor abuse liability in the treated individual. This was important because previous treatment drugs had the liability of producing their own degree of addiction. These early clinical studies into the therapeutic use of narcotic antagonists might have faded into textbook obscurity had it not been for a number of concurrent social and political events that were rapidly developing. In the years following the tragedy of President Kennedy’s assassination on November Read more […]

Behavioral Pharmacology of Narcotic Antagonists

Narcotic antagonists are currently the major pharmacological alternative to methadone for the long-term treatment of narcotic addiction. The clinical utility of antagonist treatment is undergoing continuing evaluation (). Within the last five years, there have been several comprehensive reviews of research on narcotic antagonist drugs (). This review will focus upon some recent behavioral studies of narcotic antagonist drugs in man and in animals. It is now apparent that antagonist drugs may have a number of complex behavioral effects, in addition to antagonism of the pharmacological effects of opiate drugs (). Recent explorations of the aversive properties of some antagonists () have been complemented by studies of the positive reinforcing qualities of antagonist drugs. The finding that opiate dependent monkeys will work to produce an infusion of a narcotic antagonist under certain conditions () suggests the complexity of the process of drug-related reinforcement (). Narcotic agonists and antagonists each may maintain behavior that leads to their administration. Of the several compounds which have narcotic antagonist properties), only two appear to be relatively “pure” antagonists with minimal agonistic activity. Read more […]