Archive for category Drug Dependence'

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 […]

Human Dependence on Tobacco and Opioids: Physiologic Dependence

Physiologic dependence is a factor of significance in opioid dependence and of suspected significance in cigarette smoking. There are three primary aspects of physiologic dependence. The first is important in the maintenance of opioid-taking behavior, in which the emergence of the withdrawal syndrome is correlated with increasingly intense craving scores (). Some analogous findings in animal studies are that the onset of the opioid withdrawal syndrome is correlated with increased rates of drug-taking behavior () and increases in the reinforcing efficacy of opioid drugs (). The second aspect of physiologic dependence to opioids is the increasing propensity of a person in withdrawal to become anxious and to emit aggressive and antisocial acts (). The third aspect of physiologic dependence is the phenomenon of protracted abstinence (), which, in the most rigorous use of the term, refers to physiologic withdrawal signs that are present for more than six months following the onset of opioid abstinence (). Protracted abstinence to opioids has also been well documented in animal studies (). With regard to cigarette smoking, it has been recently postulated that withdrawal phenomena occur and are similar in certain respects Read more […]

Differential Drug Effects as a Function of the Controlling Consequences

One of the central themes during the initial period in the development of behavioral pharmacology was the issue of whether motivational factors influence the effects drugs have on behavior. Though seemingly a straightforward question, the translation of this problem into an experimentally addressable form was, and continues to be, somewhat difficult. Motivational concepts almost inevitably pose formidable experimental problems, and studies designed to resolve those problems have often yielded equivocal results. Typically, however, the question has been approached experimentally by comparing the effects of various drugs on behavior controlled by different types of events, e.g., food presentation and escape from electric shock. Presumably, different events and the behavioral consequences associated with them engendered different motivational states. The influence of motivational factors as determinants of drug action should then be reflected by differential changes in overt behavior when the organism is given certain drugs. This approach had one rather substantial problem that was not always recognized. Behavioral consequences are important in several different ways, not only when they differ on some hedonic dimension, 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 […]

Drug Preference in Humans: Lorazepam

A drug’s capacity to reinforce behavior in a laboratory setting usually correlates with its dependence potential in the general population. In laboratory tests, diazepam is not an effective positive reinforcer, either in laboratory animals using drug self-administration tests () or in normal human volunteer subjects using a choice test (). The failure to find evidence for a positive reinforcing effect of diazepam in these experimental tests is inconsistent with clinical reports that diazepam is used excessively by some people. The failure to demonstrate the positive reinforcing efficacy of diazepam in an experimental situation may be due in part to the drug’s long duration of action (half-life = 24 – 48 hours). In animal self-administration studies that test the reinforcing efficacy of drugs, it has been found that benzodiazepines that have shorter durations of action are also more effective reinforcers (). In the present study, human subjects were tested for preference for lorazepam, a benzodiazepine with effects similar to diazepam but with a shorter half-life than diazepam (half-life = 12-15 hours). Method Subjects. Twelve normal healthy volunteers, aged 21 to 27 (4 males, 8 females) participated in this study. Read more […]

Psychotherapy and Naltrexone in Opioid Dependence

An issue of current importance to psychiatry is the efficacy of psychotherapy and phamacotherapy in comparison to one another and in combination. In addiction treatment, the importance of individual counseling for the successful use of opioid antagonists such as naltrexone has often been suggested but as yet there is insufficient data to support this contention. Furthermore, naltrexone efficacy studies have not controlled for the type or degree of patients’ involvement in interpersonal aspects of treatment. The present pilot study evaluated the effectiveness of naltrexone in conjunction with a high intervention treatment that included individual counseling as compared with a low intervention treatment that excluded such counseling. Method Sixty-six opioid-dependent volunteers were randomly assigned at intake to either a low intervention (N=31) or high intervention (N=35) treatment group. All subjects were over 18 years of age, had been addicted to opiates for at least one year, were free of serious medical and psychiatric illness and signed an informed consent. An attempt was made to match the two groups for level of opioid dependence immediately prior to entering the study and number of subjects who entered the study Read more […]

Measurement and Extinction of Conditioned Withdrawal-Like Responses in Opiate-Dependent Patients

As O’Brien has reviewed elsewhere in this volume (), there has been much experimental work on opiates and Pavlovian conditioning processes since Wikler’s original observations of withdrawal-like responses in drug-free patients (). Several studies have found evidence of conditioned withdrawal-like and opiate-like responses in rats, monkeys, and humans (). Addict patients viewing slides or videotapes of drug-related stimuli () or handling drug objects in a preparation ritual () experience subjective craving and withdrawal-like changes in physiological measures of skin temperature, heart rate, pupillary dilation, etc. Research from our own laboratory has demonstrated that opiate withdrawallike responses in humans can be conditioned to an arbitrary conditioned stimulus (). These studies leave little doubt that conditioned withdrawal-like phenomena exist and can be both reliably elicited and measured. They do not, however, address the clinical significance of these responses. Though Wikler (1948) proposed conditioned withdrawal as the primary cause of relapse in drug-free patients, this link has not been clinically tested and is still controversial. Based on interviews with Baltimore street addicts, McAuliffe () had recently Read more […]

Marijuana, Affect and Tolerance: A Study of Subchronic Self-Administration in Women

The study of differential tolerance development has important implications for evaluation of the abuse potential of a particular drug. Tolerance to the disruptive behavioral and physiological effects of marijuana could make it possible for experienced users to function at their “normal” level of efficiency, even after heavy, daily consumption. On the other hand, tolerance to the positive psychological effects that users variously describe as euphoric, pleasurable and consciousness-expanding, would diminish the reinforcing value of the drug at a given dose, and thereby increase the necessity of more intense or more frequent consumption to achieve previous levels of intoxication. In the light of evidence that chronic marijuana consumption may be related to impaired respiratory function and other health consequences, tolerance to these effects might prove detrimental to the user (Institute of Medicine). To demonstrate that tolerance to THC leads to increased consumption, it would be necessary to establish that: 1) reliable changes are produced by acute doses of marijuana to psychological states, behavioral performance, or physiological function; 2) these effects diminish over a period of time when marijuana is administered Read more […]

Buprenorphine, Heroin, and Methadone: Comparison of Relative’ Reinforcing Properties

Buprenorphine is a partial agonist of the morphine type. It is both a long-acting opiate antagonist, like naltrexone, and a potent opiate agonist with respect to analgesia, physiological and subjective reactions in man (). However, buprenorphine does not induce physical dependence in several species and appears to produce only minimal physical dependence in man (). Buprenorphine’s positive morphine-like agonist effects combined with its antagonist potency, low toxicity, and minimal capacity for producing physical dependence, suggested that it should be valuable for the treatment of opiate addiction (). Clinical studies have shown that buprenorphine maintenance (8 mg/ day s.c.) significantly suppressed self-administration of heroin (21 to 40.5 mg/day) by male heroin addicts over 10 days of heroin availability in comparison to buprenorphine placebo (). Buprenorphine (0.282 to 0.789 mg/kg/day i.v.) also significantly suppressed opiate self-administration in the rhesus monkey drug self-administration model (). Recent clinical studies have shown that sublingual administration of buprenorphine (1-2 mg) should be suitable for daily maintenance for the treatment of narcotic addiction (). The opiate agonist effects of Read more […]

Benzodiazepines: Drug Discrimination and Physiological Dependence

The benzodiazepines are among the most widely used of all prescribed drugs. Concern about abuse of these drugs has prompted the development of preclinical methods for assessing various pharmacological effects of diazepam-like drugs which are relevant to their abuse and dependence liability. This abstract describes results from a series of ongoing experiments to assess discriminative stimulus effects and physiological dependence-producing properties of benzodiazepines. Drug discrimination: In drug discrimination procedures, animals are trained to respond differentially depending on the nature of drug pretreatment. The procedure can provide information analogous to a human testing situation in which subjects categorize drugs with respect to their subjective effects. In ongoing drug discrimination experiments, four baboons were trained to discriminate lorazepam (1.0 mg/kg) and two baboons were trained to discriminate pentobarbital (5.6 mg/kg) in a two-lever drug versus no-drug discrimination procedure. Food delivery depended on 20 consecutive responses on one lever in sessions preceded by an intramuscular injection of the training drug (60-min pretreatment time), and on 20 consecutive responses on the other lever Read more […]