Glutamatergic Modulation of Disordered Alcohol Use

Alcohol use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered drinking. Alcohol use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this randomized, double-blind, controlled trial is to test various glutamate modulators in conjunction with motivational enhancement therapy (MET) for alcohol use disorders.

Individuals diagnosed with alcohol dependence will be randomized to receive a single infusion of glutamate modulators during week 2 while engaged in a 5-week course of MET. They will meet with staff twice weekly, except for week 2 during which they will present to the clinic three times. Clinic visits include MET sessions, psychiatric monitoring, assessments, and study procedures (e.g., medication administration).

Eligibility Criteria:
Inclusion Criteria:

* Active alcohol dependence. In the case of the use of other drugs, alcohol is designated as the primary drug. At least four heavy drinking day over the past 7 days (\>4 drinks a day for males, \>3 drinks for females) OR minimum weekly use of 35 drinks for males and 28 for females
* Physically healthy
* No adverse reactions to study medications
* 21-69 years of age
* Capacity to consent and comply with study procedures, including sufficient proficiency in English
* Seeking to reduce or stop alcohol use

Exclusion Criteria:

* Meets criteria for current major depression, bipolar disorder, schizophrenia, any psychotic illness, including substance induced psychosis, and current substance-induced mood disorder.
* Physiological dependence on another substance requiring medical management, such as opiods or benzodiazepines, excluding caffeine, nicotine, and cannabis
* Delirium, Dementia, Amnesia, Cognitive Disorders, or Dissociative disorders. Significant dissociative symptoms
* Current suicide risk or a history of suicide attempt within the past year
* Inability to safely initiate 24 hours of abstinence from alcohol; repeated inability to initiate abstinence during the trial without incurring significant withdrawal; history of severe withdrawal phenomena over the past 6 months (e.g., withdrawal-related seizure); or self-reported inability to maintain abstinence for 24 hours without substantial distress.
* Pregnant or interested in becoming pregnant during the study period
* Any of the following cardiac conditions: clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse
* Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (\>140/90), leukopenia, active hepatitis or other liver disease with elevated transaminase levels (\< 2-3 X upper limit of normal will be considered acceptable if clotting factors are normal), renal failure, epilepsy, or untreated diabetes
* Previous history of study medication misuse or abuse, and a history of an adverse reaction/experience with prior exposure to study medications
* Recent history of significant violence (past 2 years)
* First degree relative with a psychotic disorder (bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis NOS)
* obesity
* On psychotropic or other medications whose effect could be disrupted by participation in the study
* BMI \> 35