Testing the abuse liability of anxiolytic and hypnotic drugs in humans

doi:10.1016/0376-8716(91)90054-3

Drug and Alcohol Dependence

Volume 28, Issue 1, June 1991, Pages 83-111

https://doi.org/10.1016/0376-8716(91)90054-3 Get rights and content

Abstract

This paper represents a comprehensive review of laboratory studies investigating the abuse liability of anxiolytic and hypnotic drugs in humans. The subjective effects of these drugs, most of which are either barbiturates or benzodiazepines, have been measured using various self-report questionnaires and their reinforcing effects have been studied using self-administration and choice procedures. Studies using both subjective and reinforcing effects reveal orderly relations between the two main chemical classes of anxiolytic/hypnotics (e.g. barbiturates are associated with higher abuse liability than benzodiazepines), between different doses of the drugs (e.g. higher doses are usually associated with higher abuse liability) and among different compounds within a class. The subjective and reinforcing effects of barbiturates and benzodiazepines depend critically upon the subject populations that are tested and it is argued that individuals with histories of drug abuse provide a more sensitive indicator of abuse liability than healthy volunteers. Several principles of abuse liability testing are discussed, including the selection of an appropriate subject population, the use of blind drug administration procedures, the comparison of a test compound to an appropriate standard, the inclusion of a placebo and a wide range of doses of the test drug and the use of multiple measures of likelihood of abuse.

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Abuse liability assessments influence drug development, federal regulation, and clinical care. One suggested procedure to reduce variability of assessments is a qualification phase, which assesses whether study applicants adequately distinguish active drug from placebo; applicants failing to make this distinction are disqualified. The present analyses assessed differences between qualification phase qualifiers and non-qualifiers.
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Testing the abuse liability of anxiolytic and hypnotic drugs in humans

Abstract

Pharmacol. Biochem. Behav.

Drug Alcohol Depend.

Pharmacol. Biochem. Behav.

Pharmacol Biochem. Behav.

Drug Alcohol Depend.

Drug Alcohol Depend.

Am. J. Med.

Pharmacol. Biochem. Behav.

Trends Pharmacol. Sci.

Drug Alcohol Depend.

Preference for alprazolam as opposed to diazepam in benzodiazepine-dependent psychiatric inpatients

Pharmacopsychiatry

Longterm treatment with diazepam

Int. Pharmacopsychiatry

Comparison of the reinforcing properties of zopiclone and triazolam in former alcoholics

Pharmacology

Euphoria, dysphoria. Measurement of Subjective Responses

Studies on the dependence-inducing potential of zopiclone and triazolam

Pharmacology

Drug deprivation and reinforcement by diazepam in a dependent population

Psychopharmacology

Benzodiazepines as drugs of abuse and dependence

Parental alcoholism as a risk factor in benzodiazepine abuse: a pilot study

Am. J. Psychiatry

Abuse liability and clinical phar-macokinetics of alprazolam in alcoholic men

J. Clin. Psychiatry

Critical review of liability for benzodiazepine abuse among alcoholics

Am. J. Psychiatry

Assessment of the abuse liability of buspirone in recreational sedative users

J. Clin. Psychiatry

A drug preference procedure for use with human volunteers

Assessing pentobarbital preference in normal volunteers using a cumulative dosing procedure

Psychopharmacology

Lack of preference for diazepam in anxious volunteers

Arch. Gen. Psychiatry

Drug preference in normal volunteers: effects of age and time of day

Psychopharmacology

The reinforcing properties of amphetamine in overweight subjects and subjects with depression

Clin. Pharmacol. Therapeut.

Preference for pentobarbital and diazepam in normal volunteer subjects

Patterns of benzodiazepine use in Great Britain as measured by a general population survey

Br. J. Psychiatry

Zolpidem and triazolam in humans: Behavioral and subjective effects and abuse liabiity

J. Pharmacol. Exp. Therapeut.

Preference studies of triazolam with standard hypnotics in out-patients with insomnia

J. Int. Med. Res.

The assessment of the abuse potentiality of sedative/hypnotics (depressants) (methods used in animals and man)

Methods for evaluating addiction liability. (A) ‘Attitude’ of opiate addicts toward opiatelike drugs, (B) A short-term ‘direct’ addiction test

J. Pharmacol. Exp. Therapeut.

Human drug self-administration: double-blind comparison of pentobarbital, diazepam, chlorpromazine and placebo

J. Pharmacol. Exp. Therapeut.

Similarities in animal and human drug-taking behavior

Drug preference in humans: double-blind choice comparison of pentobarbital, diazepam and placebo

J. Pharmacol. Exp. Therapeut.

Human sedative self-administration: effects of interingestion interval and dose

J. Pharmacol. Exp. Therapeut.

Differential effects of diazepam and pentobarbital on mood and behavior

Arch. Gen. Psychiatry

Relative abuse liability of diazepam and oxazepam: behavioral and subjective dose effects

Psychopharmacology

Comparison of diazepam and oxazepam: preference, liking and extent of abuse

J. Pharmacol. Exp. Therapeut.

Abuse liability of benzodiazepines: a review of human studies evaluating subjective and/or reinforcing effects