Section on Human Psychopharmacology, LCTS
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
10 Center Drive, Room 10-CRC/2-2352: MSC 1540
Bethesda, MD 20892-1540

 

 Molly Zametkin, Veronica Schmidt, Jia Yan, Marion Coe, Vijay Ramchandani, Bethany Stangl, Vatsalya Vatsalya

What we do

The Section conducts studies characterizing the pharmacokinetics and CNS pharmacodynamics of alcohol in humans using behavioral, neuroendocrine, electrophysiological and functional imaging measures. These studies, conducted in social and high-risk drinkers, enable the evaluation of genetic and environmental risk factors influencing the acute and adaptive responses to alcohol. The Section is also conducting studies to develop human laboratory paradigms that can be used to screen novel potential treatments for alcoholism in terms of their ability to alter the pharmacological effects of alcohol and/or alcohol self-administration behavior.

Two alcohol administration methods form the foundation of our work: (1) the alcohol clamp, and (2) computer-assisted self-infusion of ethanol (CASE). Both methods employ intravenous (IV) administration of alcohol solutions, which when combined with a physiologically-based pharmacokinetic (PBPK) model for ethanol, results in systemic (and therefore brain) alcohol exposures that are extremely precise and well-controlled. These methods provide a unique platform for studies evaluating the influence of risk factors including sex, age, drinking history and genetic polymorphisms on alcohol responses and alcohol self-administration behavior in human laboratory studies.


Current Staff

Photo of Vijay Ramchandani

Vijay Ramchandani, PhD
Tenure-Track Investigator and Chief
telephone: 301-402-8527
email: vijay.ramchandani@mail.nih.gov

 

Vijay Ramchandani obtained his undergraduate degree in Pharmaceutical Sciences from Bombay University in India in year 1990 and Ph.D. in Pharmaceutical Sciences from Virginia Commonwealth University, Richmond, VA in 1996. From 1996 to 2002, he worked at the Alcohol Research Center at Indiana University School of Medicine, Indianapolis, IN, first as a Research Associate and then as an Assistant Scientist and Part-time Assistant Professor. In 2003, Dr. Ramchandani joined NIAAA as a Staff Scientist in the Laboratory of Clinical and Translational Studies (LCTS), and in 2007, he became Chief of the Unit on Human Physiology and Pharmacokinetics. In March 2010, Dr. Ramchandani was appointed as a Tenure-track Investigator and Acting Chief of the Section on Human Psychopharmacology in LCTS.

Photo of Vatsalya Vatsalya

Vatsalya Vatsalya, MD MS PGD
Post-Doctoral Visiting Fellow
telephone: 301.451.6968
email: vatsalyav@mail.nih.gov

 

Dr. Vatsalya is an Associate Investigator in SHP, and oversees human paradigms for computer-assisted self-administration of ethanol studying varenicline effects on consumption, age and sex influence, and genetic response; evaluating pharmacological, fMRI imaging, physiological and behavioral measures. He conducts data analysis; publication and presentation procedures for several of the ongoing protocols. His interests include clinical research focusing on treatment assessment, physiological and behavioral evaluations; geriatrics; and gene development. He is a member of Evaluation committee at Oppnet; few editorial boards and International Exposition body at NIH. Dr. Vatsalya organizes and instructs Psychopathology and Behavior Evaluation graduate coursework in the Department of Medicine at FAES. His future goals include clinical research, practice, and instruction.

 

 

Bethany Stangl, PhD

Bethany Stangl, PhD
Post-Doctoral Fellow
telephone: 301.451.9401
email: stanglbl@mail.nih.gov

 

Dr. Stangl joined the Section on Human Psychopharmacology in September 2010. She earned her undergraduate degree at Dickinson College and her PhD in cognitive neuroscience at The George Washington University where she used a clinical trials experiment to observe how DHEA and hormones influence cognitive behavior in postmenopausal women. Her current work involves the Computer-Assisted Self-Administration of Ethanol (CASE) protocol as well as a Progressive-Ratio paradigm protocol. She is interested in the relationship between the neuroendocrine system and alcohol, CRH, fMRI techniques, as well as the behavioral,especially cognitive, effects of alcohol and self-administration behavior in humans.

Jia Yan, PhD, MS

Jia Yan, PhD, MS
Post-Doctoral Fellow
telephone: 301.827.0566
email: jia.yan@nih.gov

 

Dr. Yan joined the Section on Human Psychopharmacology in October 2012 after completing an M.S. in Genetic Counseling and Ph.D. in Human and Molecular Genetics through a dual degree program at Virginia Commonwealth University. Her training integrated clinical genetic counseling experience with research on alcohol dependence using statistical genetics methods at the Virginia Institute for Psychiatric and Behavioral Genetics. Her previous work investigated the use of genetic information in clinical risk prediction for alcohol dependence. She is currently focusing on the quantitative analysis of genetic and phenotypic data in the LCTS using genome-wide and systems-based approaches.

Joshua Gowin, PhD

Joshua Gowin, PhD
Post-Doctoral Fellow
telephone: 301.451.6968
email: joshua.gowin@nih.gov

 

Dr. Gowin joined the SHP in August of 2013. He earned his M.S. in 2009 and his Ph.D. in 2011 in behavioral neuroscience and psychopharmacology from the University of Texas Health Science Center in Houston. While there he learned to use acute and chronic administration of drugs to examine behavioral, physiological and neuroendocrinological effects. Starting in 2012, he did a one year fellowship at the University of California San Diego where he became a scan operator for fMRI studies and learned to analyze imaging data. He is interested in exploring the neural correlates of risk-taking as a lens to understand pathologic behaviors such as substance use disorders and aggression.  

Molly Zametkin

Molly Zametkin
Post-Bacc IRTA Fellow
telephone: 301-451-0308
email: molly.zametkin@mail.nih.gov

 

Molly Zametkin joined the section in June 2010 and has since received her BA in psychology from The Colorado College. Molly’s responsibilities include recruiting, screening, scheduling participants, and conducting study sessions. Currently, her primary focus is the Computer-Assisted Self-Administration of Ethanol (CASE) in Humans protocol. Molly’s background is in primate research and she has also had the opportunity to study mood and anxiety disorders through NIMH. Molly interests lie in addiction, pharmacology, behavior analysis, research coordination, sociology of health, and neurophysiology.

 

Jonathan Westman

Jonathan Westman
telephone: 301.451.7605
email: jonathan.westman@nih.gov

 

Jonathan Westman received his B.A. in Psychology and History from Cornell University in May 2013 and joined the Human Psychopharmacology section shortly thereafter. Jonathan recruits and screens healthy volunteers by administering a series of interviews and psychological evaluations; in addition, he schedules and carries out experimental sessions for study protocols. Jonathan is heavily immersed in the Computer-Assisted Self-Administration of Ethanol (CASE) in Humans protocol as well as in the launch of a new protocol involving Carfentanil. Jonathan’s prior research experience includes the investigation of the physiological and behavioral effects of alcohol withdrawal in mice. Jonathan is especially interested in treatment plans for addictive behaviors and anxiety and hopes to obtain a graduate degree in clinical psychology. 

Veronica Y. Schmidt

Veronica Y. Schmidt
Research Coordinator
telephone: 301.435.9397
email: schmidtv@mail.nih.gov

 

Veronica graduated from Saint Joseph College with a B.S. in Biochemistry and minor in Psychology. She is currently working on the Varenicline protocol as a recruiter. She has experience in conducting psychological assessments and clinical study sessions. She has a strong background in research, with experiences in ophthalmology-genetic study in human paradigms at the University of Connecticut; and in treatment translational neuropharmacology at the National Institute of Mental Health. Her interests include public health, mental health and pharmacology. Her future goals are to pursue an advanced health care graduate degree and conduct clinical research, practice and instruction


Section Alumni

Elizabeth Edenberg (Summer 2003)

Molly Carroll (Summer 2004)

Mike Hoefer (2004-2005)

Nina Saxena (2005-2006)

Shilpa Kumar (2006-2007)

Satjit Brar (Summer 2007)

Seth Eappen (2007-2008)

Julnar Issa (2008-2010)

Aishini Thiyagarajan (Summer 2008, 2009, 2010)

EB Grasser (Summer 2009)

Megan Cooke (2009-2011)

Marion Coe (2011-2013)

Kaori Abe, Research Nurse Trainee, Kurihama Medical and Addiction Center, Japan (Fall 2011)

Tomoko Nakao, Research Nurse Trainee, Kurihama Medical and Addiction Center, Japan (Spring 2012)

Tohru Numano, Research Nurse Trainee, Kurihama Medical and Addiction Center, Japan (Fall 2012)

Protocols

08-AA-0178 Computer-Assisted Self-Administration of Ethanol (CASE) in Humans (PI: Vijay A. Ramchandani, PhD)

08-AA-0137 A Randomized, Double-blind, Placebo Controlled Trial (RCT) of Varenicline to Reduce Alcohol Consumption in Heavy Drinkers

11-AA-0180: Genetics of the acute response to alcohol in humans (PI: Vijay A. Ramchandani, PhD).

NIAAA Clinical Protocols & link to all NIH Clinical Protocols


Selected Publications

Original Papers:

  1. Li T-K, Beard JD, Orr WE, Kwo PY, Ramchandani VA.  Gender and ethnic differences in alcohol metabolism. Alcohol Clin Exp Res 22:771-772 (1998).
  2. Kwo PY, Ramchandani VA, O'Connor S, Amann D, Carr LG, Sandrasegaran K, Kopecky K, Li T-K.  Gender differences in alcohol metabolism: Relationship to liver volume and effect of adjusting for lean body mass. Gastroenterology 115:1552-1557 (1998).
  3. Ramchandani VA, Bolane J, Li T-K, O'Connor S.  A physiologically-based pharmacokinetic (PBPK) model for alcohol facilitates rapid BrAC clamping. Alcohol Clin Exp Res 23:617-623 (1999).
  4. Ramchandani VA, O'Connor S, Blekher T, Kareken D, Morzorati S, Nurnberger Jr. J, Li T-K.  A preliminary study of acute responses to clamped alcohol concentration and family history of alcoholism. Alcohol Clin Exp Res 23:1320-1330 (1999).
  5. Li T-K, Beard JD, Orr WE, Kwo PY, Ramchandani VA, Thomasson HR. Variation in ethanol pharmacokinetics and perceived gender and ethnic differences in alcohol elimination. Alcohol Clin Exp Res 24:415-416 (2000).
  6. O'Connor S, Ramchandani VA Li T-K. PBPK modeling as a basis for achieving a steady BrAC of 60±5 mg% within ten minutes. Alcohol Clin Exp Res 24:426-427 (2000).
  7. Ramchandani VA, Kwo PY, Li T-K. Influence of food and food composition on alcohol elimination rates in healthy men and women. J Clin Pharmacol 41:1345-1350 (2001).
  8. Li T-K, Yin S-J, Crabb DW, O’Connor S, Ramchandani VA. Genetic and environmental influences on alcohol metabolism in humans. Alcohol Clin Exp Res 25:136-144 (2001).
  9. Sato N, Lindros KO, Baraona E, Ikejima K, Mezey E, Jarvelainen H, Ramchandani VA. Gender differences in alcohol-related organ injury. Alcohol Clin Exp Res 25:49S-53S (2001).
  10. Blekher T, Beard JD, O'Connor S, Orr WE, Ramchandani VA, Miller K, Yee RD, Li T-K. Response of saccadic eye movements to alcohol in African American and non-Hispanic White college students. Alcohol Clin Exp Res 26:232-238 (2002).
  11. Morzorati SL, Ramchandani VA, Flury L, Li T-K, O’Connor S. Self-reported subjective perception of intoxication reflects family history for alcoholism when breath alcohol levels are constant. Alcohol Clin Exp Res 26:1299-1306 (2002).
  12. Blekher T, Ramchandani VA, Flury L, Foroud T, Kareken D, Yee R, Li T-K, O’Connor S. Saccadic eye movements are associated with a family history of alcoholism at baseline and after exposure to alcohol. Alcohol Clin Exp Res 26:1568-1573 (2002).
  13. Ramchandani VA, Flury L, Morzorati S, Kareken D, Blekher T, Foroud T, Li T-K, O'Connor S.  Recent Drinking History: Association with family history of alcoholism and the acute response to alcohol during a 60 mg% clamp. J Stud Alcohol 63:734-744 (2002).
  14. Morzorati SL, Ramchandani VA, Li T-K, O'Connor S. A method to achieve and maintain steady tate blood alcohol levels in rats using a physiologically-based pharmacokinetic model. Alcohol 28:189-195 (2002).
  15. Neumark YD, Friedlander Y, Durst R, Leitersdorf E, Jaffe D, Ramchandani VA, O’Connor S, Carr LG, Li T-K . Alcohol dehydrogenase (ADH2) polymorphisms influence alcohol elimination rates in a male Jewish population. Alcohol Clin Exp Res 28:10-14 (2004).
  16. Kareken DA, Claus ED, Sabri M, Dzemidzic M, Kosobud AEK, Radnovich AJ, Hector D, Ramchandani VA, O’Connor SJ, Lowe M, Li T-K. Alcohol-related olfactory cues activate the nucleus accumbens and ventral tegmental area in high-risk drinkers: Preliminary findings. Alcohol Clin Exp Res 28:550-557 (2004).
  17. Khaole NCO, Ramchandani VA, Viljoen DL, Li T-K. Systemic alcohol exposure during free-choice drinking in women with or without a child with fetal alcohol syndrome. Alcohol Alcohol 39:503-508 (2004).
  18. Plawecki MH, DeCarlo RA, Ramchandani VA, O’Connor S. Estimation of ethanol infusion profile to produce a specified BrAC time course using physiologically-based pharmacokinetic (PBPK) models. IEEE Engineering in Medicine and Biology Society International Conference Proceedings. 1:778-781 (2004).
  19. Ramchandani VA, O’Connor S, Neumark YD, Zimmermann US, Morzorati SL, de Wit H. The alcohol clamp: Applications, challenges and new Directions – An RSA 2004 symposium summary. Alcohol Clin Exp Res 30:155-164 (2006).
  20. Han J-J, Plawecki MH, Doerschuk PC, Ramchandani VA, O’Connor S. Ordinary differential equation models for ethanol pharmacokinetics based on anatomy and physiology. IEEE Engineering in Medicine and Biology Society International Conference Proceedings. (article 4029183) 1:5033-5036 (2006).
  21. Plawecki MH, DeCarlo R, Ramchandani VA, O’Connor S. Improved transformation of morphometric measurements for a priori parameter estimation in a physiologically-based pharmacokinetic model of ethanol. Biomedical Signal Processing and Control 2:97-110 (2007).
  22. Salloum JB, Ramchandani VA, Bodurka J, Rawlings R, Momenan R, George D, Hommer DW. Blunted rostral anterior cingulate response during a simplified decoding task of negative emotional facial expressions in alcoholic patients. Alcohol Clin Exp Res 31:1490-1504 (2007).
  23. Gilman J, Ramchandani VA, Davis M, Bjork JM, Hommer DW. Why we like to drink: An fMRI study of the rewarding and anxiolytic effects of alcohol. J Neurosci. 28:4583-4591 (2008).
  24. Taylor RE, Raysor BR, Kwagyan J, Ramchandani VA, Kalu N, Powell-Davis M, Ferguson CL, Carr LG, Scott DM. Alterations in ethyl alcohol pharmacokinetics during oral consumption of commercial malt liquor beverages. Alcohol Clin Exp Res 32:2074-2080 (2008).
  25. Plawecki MH, Han JJ, Doerschuk PC, Ramchandani VA, O'Connor SJ. Physiologically based pharmacokinetic (PBPK) models for ethanol. IEEE Trans Biomed Eng 55:2691-2700 (2008).
  26. Ramchandani VA, Plawecki M, Li T-K, O’Connor S. Intravenous ethanol infusions can mimic the time course of breath alcohol concentrations following oral alcohol administration in healthy volunteers. Alcohol Clin Exp Res 33:938-944 (2009).
  27. George DT, Herion D, Jones CL, Phillips MJ, Hersh J, Hill D, Heilig M,  Ramchandani VA, Geyer C, Spero DE, Singley ED, O’Malley SS, Bishai R, Rawlings RR, Kunos G. Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers. Psychopharmacology 208:37-44 (2010).
  28. Lee J, Ramchandani VA, Hamazaki K, Engleman EA, McBride WJ, Kim H-Y. A critical evaluation of influence of ethanol and diet on salsolinol enantiomers in humans and rats. Alcohol Clin Exp Res 34:242-250 (2010).
  29. Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M. A genetic determinant of the striatal dopamine response to alcohol. Mol Psychiatry 16:809-817 (2011).
  30. Roh S, Matsushita S, Hara S, Maesato H, Matsui T, Suzuki G, Miyakawa T, Ramchandani VA, Li T-K, Higuchi S. Role of GABRA2 in moderating subjective responses to alcohol. Alcohol Clin Exp Res 35:400-407 (2011).
  31. Vatsalya V, Issa JE, Hommer DW, Ramchandani VA. Pharmacodynamic effects of intravenous alcohol on hepatic and gonadal hormones: Influence of age and sex. Alcohol Clin Exp Res 36:207-213 (2012).
  32. Snell L, Ramchandani VA, Saba, L, Herion D, Heilig M, George D, Pridzun L, Helander A, Schwandt M, Phillips M, Hoffman P, Tabakoff B. The Biometric Measurement of Alcohol Consumption. Alcohol Clin Exp Res 36:332-341 (2012).
  33. Gilman JM, Smith AR, Ramchandani VA, Momenan R, Hommer DW. The effect of intravenous alcohol on the neural correlates of risky decision-making. Addiction Biology 17:465-478 (2012).
  34. Gilman JM, Ramchandani VA, Crouss T, Hommer DW. Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns. Neuropsychopharmacology 37:467-477 (2012).
  35. Kalu N, Ramchandani VA, Marshall V, Scott D, Ferguson C, Cain G, Taylor R. Heritability of level of response and association with recent drinking history in non-alcohol dependent drinkers. Alcohol Clin Exp Res 36:1034-1041 (2012).
  36. Huang M-C, Schwandt ML, Ramchandani VA, George DT, Heilig M. Impact of multiple types of childhood trauma exposure on risk of psychiatric comorbidity among alcoholic inpatients. Alcohol Clin Exp Res 36:1099-1107 (2012).
  37. Schwandt ML, Heilig MA, Hommer DW, George DT, Ramchandani VA. Childhood trauma exposure and alcohol dependence severity in adulthood: mediation by emotional abuse severity and neuroticism. Alcohol Clin Exp Res 37:984-992 (2013).
  38. Marshall VJ, Ramchandani VA, Kalu N, Kwagyan J, Scott DM, Ferguson CL, Taylor RE. Evaluation of the influence of Alcohol Dehydrogenase polymorphisms on alcohol elimination rates in African Americans. Alcohol Clin Exp Res In press, Epub: doi:10.1111/acer.12212 (2013).
  39. Leggio L, Schwandt ML, Oot EN, Dias AA, Ramchandani VA. Fasting-induced increase in plasma ghrelin is blunted by intravenous alcohol administration: A within-subject placebo-controlled study. Psychoneuroendocrinology In press. Epub: doi:pii: S0306-4530(13)00324-7. 10.1016/j.psyneuen.2013.09.005 (2013).
  40. Mitchell MC, Teigen EL, Ramchandani VA. Absorption and peak blood alcohol concentration after drinking beer, wine or spirits. Alcoholism Clinical Experimental Research. In press, 2013.

 

Reviews and Book Chapters:

  1. Ramchandani VA, Bosron WF, Li T-K. Research advances in ethanol metabolism. Pathologie Biologie 49:676-682 (2001).
  2. Ramchandani VA. Genetic aspects of alcohol metabolism. In Alcohol in disease: Nutrient interactions and dietary intake (Watson RR and Preedy VR, ed). Boca Raton, CRC Press: 187-199 (2004).
  3. Ramchandani VA, O’Connor S. Studying alcohol elimination using the alcohol clamp method. Alcohol Research and Health 29:286-290 (2006).
  4. Heilig M, Thorsell A, Sommer WH, Hansson AC, Ramchandani VA, George DT, Hommer D, Barr CS. Translating the neuroscience of alcoholism into clinical treatments: From blocking the buzz to curing the blues. Neurosci Biobehav Rev 35:334-344 (2010).
  5. Hendler RA, Ramchandani VA, Gilman J, Hommer DW. Stimulant and sedative effects of alcohol. Curr Top Behav Neurosci 13:489-509 (2013).
  6. Zimmermann US, O’Connor S, Ramchandani VA. Modeling alcohol self-administration in the human laboratory. Curr Top Behav Neurosci 13:315-353 (2013).
  7. Ramchandani VA. Genetic aspects of alcohol metabolism. In Alcohol, Nutrition and Health Consequences (Watson RR, Preedy VR, Zibadi S, ed). New York, Humana Press 15-25 (2013).

Alcohol publications can also be found using the ETOH Database

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