Neuromodulation of Trauma Memories in PTSD & Alcohol Dependence

Summary and Synthesis: Epidemiological studies have established the occurrence of high rates
of AD in persons with PTSD. Likewise, studies of alcohol/drug abuse treatment seekers have
documented high rates of trauma exposure and PTSD. The high prevalence of PTSD/AD
comorbidity is the cause of enormous human suffering, most of which either goes untreated or
is resistant to treatment efforts. Both theory and research concerning the interface between
these two disorders suggests that PTSD is associated with the initiation of excessive
alcohol use and/or the development of AD by way of an escape/avoidance behavioral mechanism
wherein escalating alcohol use is reinforced by its ability to dampen the negative emotions
and arousal associated with PTSD. If PTSD is often a primary cause of the initiation and
maintenance of AD, then clinical interventions that primarily impact PTSD should lead to
significant improvements in craving for, and use of, alcohol. The findings of two recent
treatment studies offer especially compelling support for this expectation. Drawing on both
basic neuroscience research and a developing body of suggestive clinical/applied research,
we were led to consider if the putative memory modulating properties of the adrenergic
antagonist propranolol might have therapeutic benefits for PTSD/AD comorbid individuals.
Thus, the proposed study will test the hypothesis that the strategic administration of
propranolol coupled with the elicitation/retrieval of trauma-related memories will dampen
emotional distress, alcohol craving and cue reactivity during subsequent exposure to trauma-
and alcohol-related cues. A two-week follow-up laboratory session and clinical assessment
will permit us to evaluate whether treatment benefits are maintained over time and if there
are any changes in alcohol use and PTSD symptomatology.

Inclusion Criteria:

- Participants must meet DSM-IV criteria for current alcohol dependence

- Participants must have experienced criminal victimization

- Use of birth control by female participants

- Live within a 50-mile radius of research site

- Consent to remain abstinent of all drugs and alcohol for 24 hours prior to patient
admission and follow-up

- Consent to random assignment to propanol or placebo

- Individuals must be able to provide informed consent and function at an intellectual
level sufficient to allow accurate completion of all assessment instruments.

Exclusion Criteria:

- Women who are pregnant, nursing or are of childbearing potential and not using birth
control.

- Evidence or history of significant hematological, endocrine, cardiovascular,
pulmonary, renal, gastrointestinal or neurological disease

- Significant liver impairment

- Currently taking anti-arrhythmic agents, psychostimulants or other agents known to
interfere with heart rate and skin conductance monitoring.

- Known or suspected hypersensitivity to propanol

- Individuals taking medication that could adversely interact with the study
medication, including the following: albuterol, insulin or significant inhibitors of
CYP2D6

- Individuals with bronchial asthma or chronic obstructive pulmonary disease

- Prospective participants will be excluded if they are currently receiving
exposure-based therapy for PTSD.

- Individuals with a history of or current psychotic disorder.

- Individuals with Addison's disease, Cushing's disease or other diseases of the
adrenal cortex likely to affect cortisol levels.

- Individuals receiving synthetic glucocorticoid therapy, any exogenous therapy, or
treatment with other agents that interfere with HPA axis function within one month of
the time of testing.

- Individuals with resting heart rates less than 55 bpm.