The purpose of this study is to understand the effects of the drug alprazolam (Xanax ) on anxiety.

To understand the effect of anxiety-relieving drugs on fear and anxiety, researchers often have participants anticipate unpleasant stimuli. Anticipating unpleasant stimuli increases or potentiates a simple reflex called the startle reflex. The so-called fear-potentiated startle reflex (FPS) effect may be blocked or reduced by anxiety-relieving drugs. Evidence suggests that the FPS can be mediated by two mechanisms that regulate the phasic- and sustained enhancement of startle. This study will elicit phasic and sustained FPS in participants by having them anticipate moderately painful stimuli that are administered predictably and unpredictably. The main goal of this study is to assess the affect of alprazolam on the phasic and sustained enhancement of startle.

This study comprises two pilot experiments and a main study. Participants in the study will be screened with a psychiatric history, physical examination, electrocardiogram (EKG), and blood and urine tests. Participants will four testing sessions separated by 5 to 10 days. At each session, participants will be given one of two doses of alprazolam, diphenhydramine, or placebo (an inactive pill). Questionnaires and other tests will be performed.

Condition
Healthy

Further Study Details: 

Expected Total Enrollment:  70

A lack of adequate experimental models of emotional reactions to aversive stimuli is an impediment to furthering our understanding of the psychopharmacology of fear and anxiety in humans. Finding procedures that enable us to test putative anxiety-relieving agents would greatly facilitate this type of research. The startle reflex is an ideal tool for such an endeavor. The so-called fear-potentiated startle reflex (FPS) has clear face validity, well-defined neuronal system, and cross-species generalization. In addition, in rodents the fear-potentiated startle reflex effect is blocked or reduced by drugs that are anxiolytic in humans. However, the few psychopharmacological studies conducted so far in humans have yielded inconsistent results. One possibility is that prior studies have not employed optimal designs to test the effects of anxiolytics. Our previous studies in anxious individuals and patients with anxiety disorders, as well as animal studies, suggest that the potentiation of startle by aversive states can be mediated by two distinct psychological and neurobiological mechanisms. One mediates the short-term potentiation of startle to explicit threatening cues, and the other the long-term potentiation of startle by contextual cues. We believe that benzodiazepines act preferentially on FPS to contextual cues. We have designed an experiment in humans to elicit short- and long-term FPS by having subjects anticipate unpleasant stimuli that are administered predictably or unpredictably. The specific objective of this protocol is to assess the effect of alprazolam on this short- and long-term potentiation of startle. The effect of alprazolam will be compared to placebo and to diphenhydramine (Benadryl). Diphenhydramine will be used as an active control agent to approximate the level of sedation induced by alprazolam. Following a screening procedure, subjects will be tested on four consecutive experimental sessions separated by 7-10 days. They will receive a pill containing either a placebo, a dose of 0.5 mg alprazolam, a dose of 1 mg alprazolam, or a dose up to 50 mg of diphenhydramine.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
Subjects will be healthy volunteers ages 18-45 free of current psychopathology and organic central nervous system disorders.
EXCLUSION CRITERIA:
Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizure, etc.).
Adverse reactions to benzodiazepines or antihistamines.
A past history of psychotic disorder, bipolar disorder, PTSD, major depression, social phobia, panic disorder, anorexia.
Any current psychiatric disorders, including alcohol or drug (except nicotine) abuse/dependence and anxiety disorders.
Past history of alcohol or drug abuse/dependence in the last 10 years.
Current use of psychotropic medication or an illicit substance.
Impaired hearing.
Reduced startle reactivity.
Pregnancy.
Positive results of beta-human chorionic gonadotropin testing (females only).

Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020263; 02-M-0263
Record last reviewed:  May 21, 2004
Last Updated:  November 23, 2004
Record first received:  August 16, 2002
ClinicalTrials.gov Identifier:  NCT00044096
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08