for people ages 18-50 (full criteria)
healthy people welcome
at Emeryville, California and other locations
study started
estimated completion:
Jennifer Mitchell



In this study, we seek to understand the effects of tolcapone and entacapone, FDA-approved COMT inhibitors, on reward choice and response inhibition, two measures we have previously shown to be altered in subjects with alcoholism. We now plan to test the hypothesis that COMT regulation of cortical dopamine levels is critical for regulation financial choices. Specifically, we propose that the lower levels of cortical dopamine present in individuals with the val158val COMT genotype reduces the inhibitory effect of frontal cortical areas on impulsive choice; an idea that extends previous hypotheses about the negative consequences of decreased prefrontal dopamine levels on inhibitory control. Moreover, this hypothesis suggests that inhibiting COMT may slow the degradation of dopamine and thereby decrease impulsivity.

Official Title

A Randomized, Double-Blind Study of Neural Circuit Responses to COMT Inhibitors


Drug consumption despite adverse consequences is a defining feature of human addiction (DSM-IV-TR, 2004). Impulsivity, a tendency to choose an immediate action despite delayed adverse consequences, is a major risk factor for tobacco, psychostimulant, opioid and alcohol abuse. In humans, impulsivity can be quantified by presenting subjects with a choice between a small immediate monetary reward or a larger but delayed reward. We recently found that the val158val allele for the enzyme catechol-O-methyltransferase (COMT), which is associated with more rapid cortical dopamine catabolism and thus lower cortical dopamine levels correlates with greater impulsivity and greater fMRI blood oxygen level dependent (BOLD) signal in dorsolateral prefrontal and posterior parietal cortices.

The first phase of the study will involve healthy controls. The second phase of the study will involve abstinent alcoholics matched for age, education, and gender. Subjects will range in age between 18 and 50 years old.


Impulsive Behavior Entacapone Tolcapone Catechol O-Methyltransferase Inhibitors


You can join if…

Open to people ages 18-50

  • Age between 18 and 50 years.
  • Subject is right-handed.
  • If female, subject is non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device (IUD), hormonal birth control or barrier method).
  • Subject is able to read and speak English.
  • Subject is a high school graduate.
  • Subject is able and willing to provide written and informed consent.
  • Subject is able to understand and follow the instructions of the investigator, and understand all ratings scales.
  • Subject is in good health.

You CAN'T join if...

  • Using cocaine, stimulants (other than THC, nicotine, & caffeine)amphetamines,hallucinogens, "ecstasy", opiates, sedatives, pain pills, sleeping pills or other psychoactive drugs within two weeks of the start of the study OR more than 10 times in the last year.
  • Has a current dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol.
  • Clinically significant medical or psychiatric illness requiring treatment as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician.
  • Subject has a history of major alcohol related complications within the proceeding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, etc.)
  • Liver function test ≥ 3 times normal upper limit.
  • BAC level > 0.05% at the beginning of screening visit (within margin of error of detection).
  • Has a neurological dysfunction or psychiatric disorder.
  • Has severe low blood pressure.
  • Has uncontrolled high blood pressure.
  • Regular use of any of the drugs on the tolcapone or entacapone contraindications list OR within 2 weeks of drug administration.
  • Regular use of SSRIs.
  • Has an allergy or intolerance to tolcapone or entacapone.
  • Subject has received an investigational drug within 30 days of screening visit.
  • Subject is considered unsuitable for the study in the opinion of the investigator or study physician for any other reason.

MRI Exclusion Criteria:

  • The subject has metal (metal plates, pins, wires or screws, artificial limb, joint replacement or anything that might have been inserted during an operation) in his/her body.
  • Subject has a pacemaker, defibrillator, stent, or any metal implants related to heart/blood flow problems.
  • Subject has worked with metals (ie. metallurgy, metal shaving, welding, soldering,etc).
  • Subject has been wounded with anything metal (bullet, shrapnel or metal filling).
  • Has ever gotten a piece of metal in the eye.
  • Has tattoos done with ink containing metal or permanent eyeliner.
  • Wears color contact lenses.
  • Has a hearing problem or hearing aid, cochlear implant or past ear surgery.
  • Has any irremovable dental bridges, dental plates, metal caps or any other non-removable metal in the mouth.
  • The subject is claustrophobic.
  • The subject is pregnant. (women only)
  • Has a IUD. (women only)
  • Significantly overweight.


  • UCSF: Ernest Gallo Clinic and Research Center
    Emeryville California 94591 United States
  • University of California, Berkeley
    Berkeley California 94704 United States

Lead Scientist

  • Jennifer Mitchell
    I conduct translational neuroscience research that rests at the intersection of psychology, pharmacology, and genetics. My work is focused on understanding the neural mechanisms responsible for decision-making, impulsivity, and other mechanisms in relation to drug and alcohol abuse, and on developing novel treatment strategies for these disorders.


in progress, not accepting new patients
Start Date
Completion Date
University of California, San Francisco
Study Type
Last Updated