ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01741.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01742.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractTesting of drugs for abuse liability can benefit public health. By encouraging proper therapeutic use, appropriate regulation, and development of safer and more effective drugs, such testing can benefit both consumers and pharmaceutical manufacturers. Many factors influence actual abuse; animal and human drug abuse liability testing procedures are useful, though imperfect, predictors of abuse. Three suggestions are made concerning human drug abuse liability testing: (1) that more research is needed on differences between individuals and between different subpopulations tested with these procedures (2) that actual epidemiological experience concerning abuse should be the ‘gold standard’ for assessing the validity and utility of drug abuse liability testing methods; and (3) that methods for drug abuse liability testing in humans should be introduced and used systematically to guide appropriate development, regulation, and marketing of dr

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01743.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe procedures for approving medicines have been progressively harmonized within the European Community. The authorization of medicinal products beyond 1992 will be based on a more centralized procedure, with important safeguards to ensure that there is no dilution of strict standards of quality, safety, and efficacy. Although some efforts have been attempted to coordinate the procedures for approving medicines with Japan and the United States, some important problems still remain. An example of this lack of coordination is the lack of agreement about applying abuse liability testing to psychotropic drugs. In the United States, abuse liability data are routinely used for scheduling and labeling new drugs under the supervision of the Food and Drug Administration (FDA). This agency has codified the requirements for clinical studies of potential abuse of psychotropic drugs and requires pharmaceutical sponsors to submit specific data. However, requirements within the European Community in this matter are minimal. Clinical trials on subjective effects, drug discrimination or drug preference are not requested. This situation demands more scientific interchange between officials and scientists from the FDA and their counterparts from Europe. The Committee for Proprietary Medicinal Products (CPMP) must play a major role in this coordination and interchange.

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01744.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractAssessments of the abuse potential of psychoactive drugs in preclinical and clinical studies are used in regulatory decision making process in the United States under the Controlled Substance Act (CSA) and the Federal Food, Drug, and Cosmetic Act (FD&C Act). Two types of drugs are evaluated in abuse potential studies, those being developed for a therapeutic indication by the pharmaceutical industry and illicitly manufactured ‘street drugs’ of abuse. Only the former will be considered here. In the case of drugs being pursued for marketing or are amendable to study in human subjects and are of scientific, medical, or regulatory interest, preclinical data may be inadequate for drug scheduling and marketing decisions. Preclinical data assessment can suggest hypotheses which must be validated in clinical studies. Moreover, there are limitations to the feasibility of evaluating certain drugs/dosage forms in preclinical studies. Thus, clinical studies are needed for the following scientific reasons: to validate preclinical hypotheses; to assess the time‐course of subjective effects as a function of dose and route of administration; to evaluate the generalizability of drug liking in different human subject populations; and to evaluate the effects of drugs on cognitive and affective processes. Clinical studies are also needed if a claim is made regarding reduced or no abuse potential; and lack of additive or potentiative effects with al

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01745.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

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 humanit

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01746.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

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 preve

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01747.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractClinical testing for drug abuse liability began as part of a collaborative effort to develop non‐addicting substitutes for morphine. Physical dependence capacity and euphorigenic potential were identified as the potent effects of morphine leading to abuse; quantitative measures were developed for these effects. Drugs were evaluated for morphine‐like effects using principles of bioassay. In recent years, the alterations in mood, feeling, thinking, and perception induced by drugs (subjective effects) are viewed as the effects leading to reinforcement of drug‐taking behavior and to abuse. The same procedures and methods developed for assessing these effects with opioids have subsequently been applied to other classes of drugs. At present, human drug abuse liability testing methods exist for opioids, stimulants, sedative hypnotics, serotonin agonist and antagonists, nicotine, alcohol, and caf

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01748.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractEstimates of the likelihood that a drug will be abused have generally been based on the subjective effects engendered by that drug. With the development of standardized subjective effects questionnaires in the 1960s and 1970s, researchers have been able to carefully evaluate self‐reported effects of drugs, generally making measures before and repeatedly after administration of a single dose of drug. The use of multiple doses under controlled laboratory conditions in which physiological measures are also taken, and both the investigator and the subject are blind to the dose administered, has been suggested as most likely to yield useful data about the abuse liability of a test compound. Although questions remain about the specific subjective effects measures to be used, there has been general agreement among researchers in this area that scores on scales from the Profile of Mood States, Addiction Research Center Inventory, and Visual Analog Scales which include measures of “high” or liking' all provide predictive utility. The addition of a measure of actual drug‐taking to this predictive model appears to provide important information about the conditions under which these two behaviors (self‐reported effects and drug self‐administration) vary, and strengthens the model su

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01749.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe human drug self‐administration paradigm is an extension of the animal model developed in the 1960s. The paradigm can be used to investigate the determinants and correlates of drug‐seeking and drug‐taking behavior and has proven useful in the development of medications for treating drug dependence. This paper describes the basic components of the human self‐administration model and discusses studies that illustrate some of its applications, including assessment of the reinforcing effects of drugs, analysis of behavioral and pharmacological mechanisms of drug self‐administration and measurement of the abuse liability, behavioral toxicity, and aversive effects of drugs. Some of the strengths and limitations of using the paradigm with human research subjects are also presented. It is concluded that the drug self‐administration model should not replace other measures of abuse liability testing in humans, but should be incorporated into comprehensive programs of drug abuse assessment wherev

ISSN:0952-0481    

DOI:10.1111/j.1360-0443.1991.tb01750.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY