Glutamatergic Modulation of Disordered Alcohol Use

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).

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