bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection of participants and experimental design in clinical abuse liability testing
Authors: MENDELSON JACK H. 
Published: January 2006

AbstractThe protection of participants in clinical abuse liability testing requires adherence to the basic practices of respect for persons, beneficence and justice. Informed consent procedures must ensure protection of confidentiality, specification of potential risks and benefits, and careful explanation of the nature of the research project and the procedures of the study. All participants should be assured that their participation is voluntary, and that they may freely decline or withdraw from the study. The selection of subjects for participation in clinical abuse liability testing should involve consideration of social and behavioral factors which may co‐vary with risk for substance abuse. Protection of participants also involves attempts to achieve excellence in the design and conduct of the research in order to enhance the contribution of such studies to science and humanity.
Drug abuse potential evaluation in animals
Authors: BALSTER ROBERT L. 
Published: January 2006

AbstractAnimal laboratory studies can provide useful information concerning the potential of drugs for abuse. Over the past SO years, methods have been developed for use with animal subjects which allow the evaluation of pharmacological properties of drugs which are particularly relevant to their abuse. The methods for preclinical drug abuse liability testing are reviewed under six headings: (1) establishment of the degree of pharmacological equivalence to known drugs of abuse, (2) drug discrimination studies, (3) tests of tolerance and cross‐tolerance, (4) tests of physical dependence capacity, (5) drug self‐administration tests of reinforcing effects, and (6) evaluation of toxicity and performance impairment at self‐administered doses. Preclinical studies can be helpful early in drug development to select lead compounds with low abuse potential for further study. In the case of new or already marketed medications, animal testing can often compliment and extend abuse liability evaluation in human subjects. The results of abuse potential evaluation studies can be useful in making decisions about the possible need for regulation under national and international drug laws, and thus play an important role in drug abuse prevention.
Drug metabolism and interactions in abuse liability assessment
Authors: SELLERS EDWARD M. , OTTON S. VICTORIA , BUSTO USOA E. 
Published: January 2006

AbstractThe interpretation of acute abuse liability studies and drug interaction studies would be importantly strengthened by the routine inclusion of drug concentration measurements at appropriate sampling times. Reliance on mean kinetic data misrepresents the variation in drug kinetics and fails to take experimental advantage of the natural differences in the population which may represent the extremes of abuse risk. Pharmacokinetic‐pharmacodynamic studies to better understand the relationship of plasma drug concentration, drug concentration in the receptor biophase and specific drug reinforced behaviour will ensure proper study design and yield useful theoretic information. Multi‐ and poly‐drug abuse (including heavy smoking and heavy ethanol use) are very common. Such patterns of use can have quite large effects on drug kinetics. Because of the potentially large qualitative and quantitative differences in drug metabolism and kinetics between pre‐clinical species and the human, data should be gathered at the earliest possible time with respect to human metabolic rates, patterns, and identification of inhibitors. The availability of human liver microsomes facilitates such studies.
Methods for the assessment of abuse liability of psychomotor stimulants and anorectic agents in humans
Authors: FOLTIN RICHARD W. , FISCHMAN MARIAN W. 
Published: January 2006

AbstractAlthough stimulant drugs have been available and abused for centuries, it is only recently that procedures for evaluating their liability for abuse have been developed. This methodological development relies on several converging assessment procedures, combining to reveal the resultant profile of effects. The first of these, drug self‐administration, is based on the principle that those drugs which can serve as reinforcers, maintaining behavior leading to their delivery, have a high liability for abuse. In addition, the more traditional approach to measuring abuse liability has been through assessing self‐reported effects in which standardized questionnaires are used. A variant of this, a drug liking' scale has also been used. A third focus of measurement has been the accuracy with which subjects can identify the drug they have been administered, with some laboratories developing procedures for training subjects to discriminate specific substances. The profile of effects obtained with a specific compound can then be compared to the profile obtained with prototypic stimulants such as amphetamine or cocaine. The extent to which these profiles are similar would predict relative liability for abuse. This paper describes the data collected for amphetamine and concludes that the most accurate assessment of abuse liability is obtained when an unknown drug is compared to a drug with abuse liability using as many of these measures as possible.
Drug abstinence effects: opioids
Authors: PRESTON KENZIE L. 
Published: January 2006

AbstractThe capacity to produce physical dependence is an important factor in the abuse liability of the opioids, contributing both to their reinforcing efficacy and to the negative public health consequences of abuse. Validated methods for measuring the physical dependence capacity of opioids in humans are the Direct Addiction and Substitution/Suppression tests; however, both methods require that subjects be made physically dependent on morphine or on high doses of investigational drugs. New methods need to be developed. Possibilities include assessment of acute physical dependence and the modification of existing substitution test methods for use with subjects already dependent on therapeutic agents.
Psychological deficit from excessive alcohol consumption: evidence from a co‐twin control study
Authors: GURLING HUGH M. D. , CURTIS DAVID , MURRAY ROBIN M. 
Published: January 2006

AbstractTwenty‐five pairs of monozygotic twins discordant for either the alcohol dependence syndrome or heavy drinking were studied to determine the adverse cognitive effects of alcohol. The twins and their co‐twins were well‐matched for premorbid history and personality but twins with high alcohol consumption performed significantly less well overall on cognitive testing than their co‐twins. Impaired performance in parts of the following tests was found: visual spatial ability, visual spatial recognition, Mill Hill vocabulary, Bexley Maudsley category sorting, tactual performance. The number of years of problem drinking correlated with inferior scores on subtests of the tactual performance test. This study provides further evidence that alcohol abuse produces long‐term cognitive sequelae which may not be grossly evident in clinical practice, and which may occur even at relatively low levels of intake.
The influence of setting on consumption in the balanced placebo design
Authors: WIGMORE STEPHEN W. , HINSON RILEY E. 
Published: January 2006

AbstractPrevious research using the balanced placebo design has demonstrated that instructions about alcohol content of a beverage affect consumption more than actual alcohol content. In the present experiment the balanced placebo design was expanded to include a dimension of context. The design was a 2×2×2 factorial with expectancy about alcohol content, actual alcohol content, and setting in which the experiment was conducted as factors. The setting factor involved conducting the experiment either in a laboratory setting typical of most balanced placebo research or in an actual bar‐room. Results obtained in the laboratory setting replicated the basic finding that subjects consumed more beverage when they believed it contained alcohol than when they believed it did not contain alcohol, regardless of actual alcohol content. Consumption in the bar‐room setting was higher than in the laboratory setting, and most importantly, consumption was not differentially affected by instruction about alcohol content or actual alcohol content. These results demonstrate the important role of setting on beverage consumption, and suggest the need to investigate factors thought to affect consumption in natural drinking environments.
Centre for behavioural research in cancer
Authors: HILL DAVID , BORLAND RON , KARAZIJA BRIGITTE 
Published: January 2006

AbstractThe Centre for Behavioural Research in Cancer (CBRC) is one of two research centres housed at the Anti‐Cancer Council of Victoria, the other being an epidemiological research centre. The CBRC's main focus for research is in smoking behaviour. A feature of the Centre is its close organisational and professional links with Victoria's large publicly funded smoking prevention programme. This provides opportunities to conduct programme‐related research, to influence the nature of tobacco reduction interventions and to evaluate outcomes.
Control versus abstinence in the treatment of pathological gambling: a two to nine year follow‐up
Authors: BLASZCZYNSKI A. , McCONAGHY N. , FRANKOVA A. 
Published: January 2006

AbstractA structured gambling interview schedule, the Eysenck Personality Questionnaire, Spielberger's State‐Trait Anxiety Inventory, Zuckerman's Sensation Seeking Scale and Beck Depression Inventory were administered to 63 out of 120 pathological gamblers who had 5 years previously completed a behavioural treatment for uncontrollable gambling behaviour. Results indicated that both abstinence and controlled gambling outcomes were associated with continued improvement in self‐report and psychological indices of social functioning and psychopathology. Response to treatment was associated with a reduction in arousal levels, anxiety and depression. Uncontrolled gamblers failed to show post‐treatment changes on parameters of improvement. It was concluded that abstinence is not the only possible therapeutic outcome in behavioural treatment and further, that controlled gambling is not a temporary response which is followed by a return to continued uncontrollable gambling.
Alcohol abuse by patients undergoing methadone treatment programmes
Authors: STASTNY D. , POTTER M. 
Published: January 2006

AbstractTo study the prevalence of problem drinking among patients undergoing methadone treatment programmes, 170 patients were assessed using the self‐administered alcohol screening test (mSAAST). Fifty‐three (31.9%) patients scored 7 or more on the mSAAST, indicating actual or potential drinking problems. There was a slight tendency for these to be male. Patients who abused alcohol also tended to use benzodiazepines irrespective of sex. The results of the study seem to indicate that the prevalence of dual alcohol and opiate use is high amongst patients attending drug dependency units. Furthermore comprehensive research is required in order to plan effective treatment for these dual addicted patients.
Suicide among hospital‐treated alcoholics in Scotland, 1974–83
Authors: KREITMAN N. B. 
Published: January 2006

AbstractTwo cohorts of suicide (and undetermined deaths) in Scotland for the quinquennia 1974–78, 1979–83 were investigated. A national record linkage exercise was carried out relating the deaths to admissions for alcoholism in the preceding 5 years (minimum) to 10 years (maximum). No differences were found between the cohorts in socio‐demographic or clinical characteristics at the time of initial admission. The survival lime as measured from either first admission or from last discharge to death was appreciably longer in the second quinquennium. This improvement might reflect changes in the patterns of services provided for alcoholics, especially the increased emphasis on the extra‐mural care.
The influence of stress on psychopharmacological responses to nicotine
Authors: BALFOUR DAVID J. K. 
Published: January 2006

AbstractThis essay considers the mechanisms which may mediate the apparent anxiolytic properties of nicotine and which are thought to be responsible for the ‘calming’ effect of tobacco smoke experienced by many smokers. It summarizes the evidence that, in many tests for anxiolytic activity, the effects of nicotine do not resemble those of established anxiolytic drugs such as diazepam and concludes that it is likely that neural systems other than those which mediate the responses to the benzodiazepines are responsible for the putative anxiolytic properties of nicotine. Circumstantial evidence which suggests that the increase in mesolimbic dopamine secretion evoked by nicotine may not only be rewarding per se but may also contribute to the ability of the drug to alleviate the effects of stress is presented. The essay also summarizes results which suggest that chronic nicotine evokes changes in the mesolimbic dopamine system which resemble those seen in animals treated chronically with antidepressant drugs and proposes that the mechanisms which mediate the ability of antidepressant drugs to alleviate the effects of stress may also mediate the apparent anxiolytic properties of nicotine. The possible consequences of this hypothesis for future research are considered.
Understanding brain mechanisms in nicotine reinforcement
Authors: CORRIGALL WILLIAM A. 
Published: January 2006

AbstractCurrent understanding of the mechanisms through which nicotine acts to reinforce behavior is limited. Demonstrated interactions between nicotine and the mesolimbic dopamine system have provided the impetus for investigations of the role of this particular brain pathway in nicotine reinforcement, and preliminary studies do indeed suggest that the dopamine system might be involved in self‐administration of nicotine. However, there are clearly other possible brain sites and neurotransmitter mechanisms that could be critical to reinforcement processes for nicotine. This article proposes that a broadly‐based attack on the question of nicotine reinforcement would be the most fruitful; basic biological research should aim to verify the involvement of the mesolimbic dopamine system, but also to elucidate other candidate brain systems that may contribute to the reinforcing properties of nicotine.
Behavioural pharmacology of nicotine: multiple mechanisms
Authors: STOLERMAN IAN P. 
Published: January 2006

AbstractIt is widely accepted that nicotine serves as a major reinforcer of tobacco use, but how it does so is obscure. Little is known about the nature of the reinforcing effect of nicotine in psychobiological terms, or about the mechanism of reinforcement at the level of neuropharmacology. Several ideas about the nature of the reinforcement are current, including mood changes such as euphoria, learning, memory and attention improvements, ability to help smokers deal with or adapt to stressors, and capacity to terminate symptoms of a nicotine withdrawal syndrome. These psychobiological effects are not mutually exclusive; different effects may be important for different people, or for the same person under different circumstances. Similarly, the neuropharmacology of nicotine reinforcement remains largely unexplored; nicotinic‐cholinergic receptors seem to play a primary role but evidence implicating particular subtypes of nicotine receptor is not available. Evidence points to the release of dopamine as an important link in the chain of events that transduce effects at nicotinic receptors into behaviour and nicotine‐seeking responses, but the dopamine hypothesis addresses only one part of a complex system. The possibility has to be faced that neuropharmacologically, several mechanisms are involved that parallel the several psychobiological effects mentioned above; multiple types of receptor, brain structures and indirectly activated neurotransmitter systems may contribute to the maintenance of nicotine‐seeking behaviour.
Beneficial effects of nicotine
Authors: JARVIK MURRAY E. 
Published: January 2006

AbstractNicotine in tobacco brings illness and death to millions of people. Yet nicotine in its pure form has the potential to be a valuable pharmaceutical agent. Nicotine fairly specifically binds to the cholinergic nicotinic gating site on cationic ion channels in receptors throughout the body. This action stimulates the release of a variety of neurotransmitters including especially catecholamines and serotonin. When chronically taken, nicotine may result in: (1) positive reinforcement, (2) negative reinforcement, (3) reduction of body weight, (4) enhancement of performance, and protection against: (5) Parkinson's disease (6) Tourette's disease (7) Alzheimers disease, (8) ulcerative colitis and (9) sleep apnea. The reliability of these effects varies greatly but justifies the search for more therapeutic applications for this interesting compound.
The development of dependence on smoking in children
Authors: McNEILL ANN D. 
Published: January 2006

AbstractThe development of dependence on smoking has been largely unexplored and has theoretical importance and implications for interventions aimed at interrupting the early stages of smoking behaviour. Data are presented which indicate the importance of the first few cigarettes. The development of a regular smoking pattern had previously been reported to take about 2 years and involve a progression through a series of stages from smoking for psychosocial motives, to smoking for a positive nicotine effect and finally for some smokers, smoking to avoid withdrawal. Results from a small scale study with girls are described which give no support to the notion of any such well‐defined stages in the novice smoker's career. Inhalation was apparent from early on indicating that nicotine can play an active role in reinforcing smoking from a very early stage. Furthermore, the majority of the young smokers perceived themselves to be dependent on their cigarettes. The nature of any positive reinforcement was unclear, the dependence‐producing potential of smoking appearing to be largely due to relief of unpleasant feelings. These findings need to be replicated and the paper highlights other key areas in this field for future research.
Inter‐relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking
Authors: ROSE JED E. , LEVIN EDWARD D. 
Published: January 2006

AbstractResearch on smoking cessation has increasingly focussed on pharmacological aspects of nicotine and nicotine withdrawal. However, cigarette smoking also provides a characteristic set of sensory cues. These sensory aspects of smoking are important to address in that they may be potent conditioned reinforcing stimuli linked to the actions of nicotine. The repetition of the smoking act thousands of times per year by a moderately heavy smoker leads to a strong conditioned association between the sensory aspects of smoking (the putative CS) and the pharmacological effects of nicotine (the putative UCS). Strategies for disrupting CS‐UCS associations may be useful in developing more effective smoking cessation treatments. These include: counterconditioning of the CS; presenting the CS alone; presenting the CS with the UCS but pharmacologically blocking the UCS; and presenting the CS and UCS in an unconnected fashion. The role of sensory cues in alleviating craving for cigarettes is discussed, and specific techniques for duplicating relevant sensory aspects of smoking without delivering significant doses of nicotine are described. The combination of nicotine and nicotinic antagonists to block primary reinforcement and hasten extinction of conditioned reinforcement is also considered.
Conceptual and methodological considerations for tobacco addiction research
Authors: GRUNBERG NEIL E. , ACRI JANE B. 
Published: January 2006

AbstractThe 1988 Surgeon General's Report on nicotine addiction has research and treatment implications. It focuses clinical treatments on tobacco use as an addiction and highlights the importance of examining actions of nicotine relevant to dependence. It also indicates the value of comparing the pharmacologic and behavioral processes underlying use of nicotine with other addictive drugs. This essay points out gaps that remain in our understanding of nicotine addiction. For example, the exact mechanisms underlying nicotine addiction are unknown. Also, the reasons for individual differences in initiation, withdrawal, relapse and reinforcing effects of tobacco use are not understood. Research designed to address these issues should be problem‐driven and multidisciplinary. Parallel human and animal studies that include unconditioned as well as conditioned behaviors are particularly valuable.
The focus and conduct of clinical trials
Authors: WEST ROBERT 
Published: January 2006

AbstractThis paper discusses some issues regarding how putative stop‐smoking treatments should be evaluated. Preliminary evaluations of treatments have used withdrawal symptoms as a surrogate for abstinence in an attempt to decide those treatments on which to carry out expensive full‐scale clinical trials. However, withdrawal symptom severity has not been shown to relate to long‐term abstinence in any prospective studies. Until a better understanding of the relationship between withdrawal symptoms and abstinence is obtained withdrawal symptoms cannot be considered an appropriate surrogate for abstinence. Research is needed into what pattern of short‐term abstinence provides the best predictor of long‐term abstinence. Evidence from carbon monoxide validation of short‐term abstinence raises doubts about whether minor lapses back to smoking are likely to lead to full blown relapse. Further research into the use of expired‐air CO in validation of claims of abstinence is required. Finally, the traditional clinical trials format is not well suited to evaluation of treatment programmes with a large behavioural component. An alternative based on the principles underlying biological evolution is proposed.
Superior outcome of females over males after brief treatment for the reduction of heavy drinking: replication and report of therapist effects
Authors: SANCHEZ‐CRAIG MARTHA , SPIVAK KAREN , DAVILA RAFAELA 
Published: January 2006

AbstractThe procedures and findings of a previous study were replicated. Sixty‐one men and 35 women were randomized to one of three treatments: Manual: three sessions of instructions in use of a manual describing a step‐by‐step method for attaining abstinence or moderate drinking. Guidelines: three sessions of advice using a pamphlet summarizing the contents of the manual. Therapist: application of the step‐by‐step method in an indefinite number of sessions. At 3–month follow‐up, the number of Moderate drinkers was again significantly higher among women than men in the Guidelines (77% versus 24%) and Manual conditions (75% versus 33%), but not in the Therapist condition (50% versus 53%). Again, at 1–year more women than men were Moderate drinkers in all conditions (69% versus 31% overall). Changes from baseline in GOT, MCV, and the Digit Symbol Test corroborated the clients' reports of drinking. In this study the more experienced therapists had significantly lower rates of client dropout than the less experienced. Clinical and research implications of the findings are discussed.