Bankole A. Johnson

Education

  • MD, University of Glasgow
  • board certification, Royal College of Psychiatrists
  • Mphil, University of London
  • PhD, University of Glasgow
  • board certification, American Board of Psychiatry and Neurology
  • DSc,FACP,FRCP,MB, University of Glasgow

Primary Appointment

  • Chair, Psychiatry and Neurobehavioral Sciences

Contact

Research Interest(s)

Integration of the Study of Brain Functions and the Behavioral Aspects of Addiction Medicine

Research Description



My research focus is in the neuropsychopharmacology of addiction.  My work integrates the neuroscience and behavioral aspects of addiction medicine, and seeks to develop an understanding of the basic underpinnings of drug-seeking behavior and to devise effective treatments.  The role and interaction between midbrain monoamine systems, particularly serotonin (5-HT), gamma-aminobutyric acid (GABA) / glutamate, and dopamine (DA), have been central to my research.

Ranging from basic human laboratory neuropharmacology to clinical trials, my research has concentrated on the programmatic development of medications to treat substance abuse disorders.  As an example, I was the first to demonstrate the effectiveness of the 5-HT3 antagonist, ondansetron, in reducing the rewarding effects of alcohol in the human laboratory.  In 2000, in a single-site NIAAA-funded clinical trial of over 300 alcoholics, I discovered that ondansetron significantly improves the drinking outcomes of early-onset alcoholics (EOA).  I hypothesize that the mechanism involved is that specific 5-HT3 receptor antagonism ameliorates the underlying 5-HT abnormality associated with EOA, thereby resulting in improved drinking outcomes.  Future studies will test this hypothesis, using positron emission tomography (PET), to determine directly the extent to which 5-HT functional abnormalities predict ondansetron treatment response.  Additionally, molecular genetic studies will be used to determine whether certain serotonin transporter-associated polymorphisms are associated with EOA and ondansetron treatment response.

In 2003, I made the discovery that topiramate (a GABA facilitator and glutamate antagonist) is an effective treatment for alcoholism. This discovery opens up a new mechanistic avenue for developing more potent pharmacological treatments for alcoholism.

Recently, I have incorporated neuroimaging evaluations into my drug interaction studies to identify the site-specific effects of abused drugs and to evaluate the effectiveness of potential medications for the treatment of addictive processes.  My research group has successfully established, for the first time in the U.S., an innovative quantitative approach to single photon emission computerized tomography (SPECT) for assessing cocaine-induced brain ischemia.  I have identified a promising agent, isradipine, a dihydropyridine-class calcium channel antagonist, for the prevention of cocaine-induced brain ischemia.  Future studies will determine whether isradipine's anti-ischemic effects generalize to other psychostimulants, and clarify DA's role in this process. Clinical studies will be used to determine isradipine's clinical effectiveness in treating cocaine addicts with brain ischemia.

Currently, my projects involve the areas of clinical trials, human laboratory, neuroimaging studies, and molecular genetics.  These are summarized below:

I am currently conducting: a) an extension to my NIAAA-funded clinical trial to determine the effectiveness of ondansetron, a 5-HT3 antagonist, in the treatment of subtypes of alcoholic.  Following upon the results of effectiveness of ondansetron for the treatment of EOA, my focus is to determine whether this type of alcoholic has functional or structural abnormalities at the serotonin transporter. The structural studies involve collaborative links with the molecular genetics center of excellence at UT-Austin, and include the genotyping of families of alcoholics who respond to ondansetron.  The functional studies are a logical extension of collaborative studies with investigators in the biochemical laboratory within the Department of Psychiatry, and planned collaborative research in neuroimaging; and b) an NIAAA-funded collaborative grant to determine the safety and efficacy of combined naltrexone (an opiate antagonist) and acamprosate (a facilitator of GABAergic function) for the treatment of alcoholism.  Together, these studies form the backbone of the clinical medications development operation.  In addition, my research group is conducting two separate clinical studies in cocaine and alcohol addiction to determine the efficacy of the GABAergic facilitator, topiramate.

In the human laboratory, I am conducting a phase I toxicology study funded by NIAAA to understand the effects of naltrexone and acamprosate on hepatic and renal function in alcohol-dependent individuals.  This phase I study forms the safety background for large-scale double-blind studies to be conducted across 11 U.S. centers over the next several years. This repeated dosing drug interaction study builds upon my experience with conducting pharmacological and kinetic studies under carefully controlled laboratory conditions.

In neuroimaging, I am extending my previous work with isradipine in a NIDA-funded PET imaging study to characterize and establish the anti-ischemic effects of isradipine. In addition, this study aims to assess the effects of isradipine on cocaine-induced changes in cardiovascular and cognitive function. This study systematically continues a programmatic series of research to develop effective preventative agents for stroke in cocaine addicts.

My goals in neuropsychopharmacology are: to understand basic bio-behavioral mechanisms of brain disorders and to devise effective treatment strategies; to disseminate scientific knowledge and discoveries, and to develop promising scientists in the field.

Selected Publications

  • Ait-Daoud N, Roache J, Dawes M, Liu L, Wang X, Javors M, Seneviratne C, Johnson B. Can serotonin transporter genotype predict craving in alcoholism? Alcoholism, clinical and experimental research. 2009;33(8): 1329-35. PMID: 19426172 | PMCID: PMC2747793
  • Seneviratne C, Huang W, Ait-Daoud N, Li M, Johnson B. Characterization of a functional polymorphism in the 3' UTR of SLC6A4 and its association with drinking intensity. Alcoholism, clinical and experimental research. 2008;33(2): 332-9. PMID: 19032574 | PMCID: PMC2657929
  • Penberthy J, Ait-Daoud N, Breton M, Kovatchev B, DiClemente C, Johnson B. Evaluating readiness and treatment seeking effects in a pharmacotherapy trial for alcohol dependence. Alcoholism, clinical and experimental research. 2007;31(9): 1538-44. PMID: 17624996