Co-Morbid Alcoholism & Anxiety

Alcohol dependence (i.e., alcoholism) is a medical condition which affects over 18 million people in the United States alone and accounts for 4% of the disease burden worldwide (Ezzati et la., 2002). Approximately 2.2 million (of the 18 million Americans that abuse or are dependent on alcohol) seek treatment for their alcohol problems. Unfortunately, such treatments are expensive, and in many cases, ineffective when using currently available therapeutic and behavior-modifying approaches. More than 75% of the alcoholics that attempt abstinence relapse back to drinking within the first year of initiating therapy using currently available therapeutic and behavior-modifying approaches. [Daley, DC and Marlatt GA. Relapse prevention. In: Lowinson JH, Ruiz P, Millman RB, Langrod JG, eds. Substance Abuse: A Comprehensive Textbook. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2005:772-785.]

Excessive alcohol drinking to reduce cyclic anxiety or to reduce the anxiety produced by alcohol abstinence, results in a co-morbid psychiatric condition and can significantly complicate treatment. GABAergic mechanisms have been implicated in the regulation of alcoholism and in the physical (e.g., tremor, seizures) and motivational (e.g., anxiety, anhedonia) aspects of alcohol withdrawal referred to as negative affective states.

We hypothesize that our novel mixed agonist-antagonist aza-beta carboline compounds can help in the treatment of both alcoholism and the negative states associated with termination of chronic drinking. In addition, we also believe from our early data, that these compounds will not be toxic or have abuse potential.

Our four lead compounds have been synthesized and have undergone an initial animal study with genetically selected alcohol-preferring (P) rats. These rats have been trained to lever press for alcohol (20 proof) in an excessive binge alcohol drinking model, and their blood alcohol concentration (BAC) typically exceed 0.08 per cent or above, the legal intoxication limit in most states in the U.S.A.. Early data shows a significant reduction in alcohol drinking in these rodents in three of the four compounds.

Additional compound synthesis is underway as well as the design and implementation of additional rodent and non-human primate studies.