The application of drug discrimination (DD) procedures to human subjects has been successful with stimulant and opioid drugs. These discriminations are orderly, pharmacologically specific, and are consistent with findings from non-human studies. Additionally, these studies typically show concordance between DD measures and self-reports of drug effect. Despite their widespread use and abuse, benzodiazepines (BZD) and other sedative hypnotics have yet to be investigated in the human DD paradigm. This project will develop a behavioral DD paradigm for laboratory use with humans and will use this paradigm to comparatively evaluate the discriminative stimulus characteristics of BZD and other sedative hypnotics. Ultimately, the usefulness of this paradigm will be determined by its pharmacologic specificity; that is, a highly specific discrimination will permit careful characterizations of the similarities and differences between BZD and other sedative-hypnotic compounds, while a drug-specific or a non-specific discrimination would have limited usefulness in this regard. In this project, the specificity of the discrimination will be determined by employing progressively more stringent tests across six studies. Study 1 will first develop the procedure and, if necessary, manipulate dose, drug, instructions and the number of training sessions to establish a discrimination between triazolam and placebo. This study will then test whether d-amphetamine is labeled as triazolam or placebo and, thus, establish whether the trained discrimination is more specific than a drug vs. no-drug discrimination. Studies 2-4 will test whether amitriptyline, buspirone, hydromorphone, pentazocine, phenobarbital and secobarbital will be labeled as triazolam or placebo and, thus, establish whether the discrimination is more specific than a sedative vs. nonsedative discrimination. Studies 5-6 will test whether chlordiazepoxide, clonazepam, diazepam, and lorazepam will be labeled as triazolam and, thus, establish whether the discrimination is drug specific. Overall, this project will thoroughly characterize the specificity of the trained discrimination and determine its utility for the study of BZD pharmacology. Additionally, the concordance between, DD and self-reports measures will be examined and, thus, test the widely held assumption that these measures are comparable. The development of a human DD procedure for studying BZD will provide an empirical tool to 1) examine the interoceptive stimulus effects of BZD and how these effects vary across different drugs, doses, populations and situations, 2) understand the neuropharmacology of BZD effects in humans, and 3) screen new anxiolytic, hypnotic, and anticonvulsant drugs for abuse liability.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA006205-03
Application #
3212781
Study Section
Special Emphasis Panel (SRCD (18))
Project Start
1990-03-01
Project End
1993-02-28
Budget Start
1992-03-01
Budget End
1993-02-28
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Smith, B J; Bickel, W K (2001) Effects of alprazolam, caffeine, and zolpidem in humans trained to discriminate triazolam from placebo. Drug Alcohol Depend 61:249-60
Smith, B J; Bickel, W K (1999) Comparing single and cumulative dosing procedures in human triazolam discriminators. J Exp Anal Behav 71:417-37
Smith, B J; Bickel, W K (1999) The novel-response procedure in humans. Pharmacol Biochem Behav 64:245-50
Smith, B J; Bickel, W K (1999) Flumazenil discrimination by humans under a two-response and a novel-response procedure. J Pharmacol Exp Ther 291:1257-68
Oliveto, A H; Bickel, W K; Hughes, J R et al. (1997) Functional antagonism of the caffeine-discriminative stimulus by triazolam in humans. Behav Pharmacol 8:124-38
Kamien, J B; Bickel, W K; Smith, B J et al. (1997) Secobarbital in humans discriminating triazolam under two-response and novel-response procedures. Pharmacol Biochem Behav 58:983-91
Oliveto, A H; Bickel, W K; Kamien, J B et al. (1994) Effects of diazepam and hydromorphone in triazolam-trained humans under a novel-response drug discrimination procedure. Psychopharmacology (Berl) 114:417-23
Kamien, J B; Bickel, W K; Hughes, J R et al. (1993) Drug discrimination by humans compared to nonhumans: current status and future directions. Psychopharmacology (Berl) 111:259-70
Rush, C R; Higgins, S T; Hughes, J R et al. (1993) A comparison of the acute behavioral effects of triazolam and temazepam in normal volunteers. Psychopharmacology (Berl) 112:407-14
Bickel, W K; Oliveto, A H; Kamien, J B et al. (1993) A novel-response procedure enhances the selectivity and sensitivity of a triazolam discrimination in humans. J Pharmacol Exp Ther 264:360-7

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