Topiramate's Effects on Heavy Drinking

The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI) to examine the effects of topiramate on brain and behavioral responses in heavy drinkers to appetitive alcohol reminders (cues that motivate continued alcohol use and relapse). This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.

This project is a double-blind, randomized, placebo-controlled study of topiramate's effects on brain and behavior responses in heavy drinkers. Eligible volunteers who meet study criteria will be randomized to receive either topiramate or placebo with weekly visits and medication management sessions. Participants will complete two magnetic resonance imaging sessions. The first scan session will occur prior to starting study drug, and the second scan will occur following six weeks of study drug. This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.

Eligibility Criteria:
Inclusion Criteria:

* Physically healthy, as determined by a comprehensive physical examination and approval of the study physician, males or females who drink alcohol, ages 18-60.
* Average weekly ethanol consumption of \>24 standard drinks for men, or \>18 standard drinks for women.
* Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 2 years postmenopausal) or of child bearing potential but practicing a medically acceptable method of birth control. Examples of medically acceptable methods for this protocol include: the birth control pill, intrauterine device, injection of Depo-Provera, Norplant, contraceptive patch, contraceptive ring, double-barrier methods (such as condoms and diaphragm/spermicide), male partner sterilization, abstinence (and agreement to continue abstinence or to use an acceptable method of contraception, as listed above, should sexual activity commence), and tubal ligation.
* Provide voluntary informed consent.
* Must be able to read. \[Subjects are required to be able to read because there are several self-administered measures that they must read, understand and provide written answers.\]
* Intelligence quotient of ≥ 80.

Exclusion Criteria:

* Current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation.
* History of head trauma or injury causing loss of consciousness, lasting more than five (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
* Current major DSM-IV Axis I diagnoses other than alcohol use disorder (except nicotine use disorder).
* Presence of magnetically active irremovable prosthetics, plates, pins, permanent retainer, bullets, etc. (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
* History of a serious psychiatric illness including psychosis, bipolar disorder, or suicidal or homicidal intent.
* Current treatment with carbonic anhydrase inhibitors.
* Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.
* Current regular treatment with psychotropic medications (e.g., benzodiazepines, antidepressants), which affect neurotransmitter systems or a medication being used to treat alcohol use disorders (e.g., naltrexone, acamprosate).
* Vision problems that cannot be corrected with glasses.
* Body Mass Index (BMI) greater than or equal to 34, body girth greater than 52 inches and a head girth greater than 25 inches.
* History of stroke and/or stroke related spasticity.
* History of glaucoma or kidney stones.
* HIV positive.
* History of seizures.
* History of topiramate treatment for alcohol use disorder and report no treatment response.
* Current DSM-5 diagnosis of alcohol use disorder that is clinically too severe to permit them to participate in a research trial in which the goal is to stop or reduce drinking.