Examining the Role of Negative Emotional States on Sedative Drug Use in Individuals With Post-Traumatic Stress Disorder

PTSD is a psychiatric illness that occurs following a traumatic event in which there was
threat of injury or death to an individual. Common symptoms of PTSD include anxiety, stress,
and tension. Some individuals with PTSD use benzodiazepines, a type of sedative medication,
or alcohol to alleviate the anxiety associated with the disorder. Past research has shown
that the negative feelings experienced by individuals with PTSD may increase the reinforcing
effects of antidepressant drugs. Feelings of anxiety act as a stimulus, which leads to drug
use; in turn, the anticipated or actual decrease in distress reinforces the drug-taking
behavior. Greater amounts of sedative drugs are then needed to decrease subsequent stress
and anxiety. The purpose of this study is to understand how negative emotional states affect
the reinforcing effects of sedative drugs in individuals with PTSD.

This study will enroll two types of individuals, both of whom have been exposed to an
emotional trauma and report using alcohol to reduce emotional distress but who differ in
their subsequent development of PTSD. Participants will take part in an initial screening
session which will include a physical examination, standardized psychological
questionnaires, and review of medical and drug histories. Once enrolled, each participant
will take part in 8 experimental session days, with each day of testing separated by at
least 48 hours. At the beginning of each session, a breathalyzer and urine test will be used
to screen for the presence of alcohol and drugs. On Day 1, participants will take part in an
orientation session to familiarize themselves with the laboratory and study procedures. On
Days 2 through 4, participants will receive varying doses of alcohol, a placebo drink, a
placebo drug, and alprazolam, a type of benzodiazepine medication. On Days 5 through 8,
participants will take part in experimental challenges designed to induce various emotional
states, including arousal, anxiety, aggression, and anger. They will also complete a
monetary reward task to measure the reinforcing effects of drugs. Participants will complete
questionnaires several times each day to assess anxiety, anger, drug effects, and drug
cravings. Heart rate will be monitored with an electrocardiogram, and electrodes placed on
the skin will measure other physiologic measures throughout each session. Participants will
receive compensation for completing each experimental session.

Inclusion Criteria:

- Diagnosis of PTSD with anxiety symptoms, as determined by a score greater than 14 on
the Hamilton Anxiety Rating Scale, or a score greater than 18 on the Profile of Mood
States-Tension Anxiety Rating Scale

- Experiences frequent and intense PTSD symptoms

- Able to spend 6 hours at a time in the research laboratory

- If a trauma control participant, must have experienced a trauma that meets criterion
A for PTSD, but has never developed PTSD

- Willing to use contraception throughout the study

Exclusion Criteria:

- Females who meet DSM-IV diagnostic criteria for premenstrual dysphoric disorder

- Females who report premenstrual distress that motivates them to use alcohol for
relief

- History of bipolar affective disorder, any psychotic disorder, current major
depressive episode, or current primary non-PTSD anxiety disorder (individuals with
Axis II diagnoses will not be excluded)

- Currently enrolled in psychodynamic or cognitive-behavioral therapy

- Current unstable medical illness

- Current medical illness treated with psychoactive drugs (e.g., beta blockers)

- Current medical illness with complicating psychiatric symptoms (e.g., thyroid
disease)

- Requires use of certain medications

- Current or past history of illicit substance dependence, other than past marijuana
abuse or dependence

- History of tobacco dependence

- Failure to provide a drug-free urine sample prior to study entry

- Smokes more than one pack of cigarettes per day or drinks beverages totaling more
than 500 mg of caffeine per day

- Pregnant