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Comparison of 50- and 100-g l-tryptophan depletion and loading formulations for altering 5-HT synthesis: pharmacokinetics, side effects, and mood states

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Abstract

Rationale

Differences in 5-hydroxytryptamine (5-HT) function have been the subject of extensive research in psychiatric studies. Many studies have manipulated l-tryptophan (Trp) levels to temporarily decrease (depletion) or increase (loading) 5-HT synthesis. While most researchers have used a 100-g formulation, there has been ongoing interest in using smaller-sized formulations.

Objectives

This study examined the time course of multiple plasma indicators of brain 5-HT synthesis after a 50-g depletion and loading as a comparison to the corresponding 100-g formulations that are typically used.

Materials and methods

Plasma was collected from 112 healthy adults at seven hourly intervals after consumption of either a 50- or 100-g depletion or loading. Self-ratings of mood and somatic symptoms were completed before and after Trp manipulations.

Results

The primary findings were that (1) the 50- and 100-g formulations produced the expected changes in plasma indicators after both depletion (−89% and −96%, respectively) and loading (+570% and +372%, respectively); (2) the 100-g depletion showed more robust effects at the 4, 5, and 6 h measurements than the 50-g depletion; (3) there was significant attrition after both the 100-g depletion and loading, but not after either of the 50-g formulations; and (4) both the 50- and 100-g depletions produced increases in negative self-ratings of mood and somatic symptoms, while loading significantly increased negative ratings after the 100 g only.

Conclusions

There are important considerations when choosing among formulation sizes for use in Trp manipulation studies, and the complete 7-h time-course data set of the typical plasma Trp measures presented here may help researchers decide which methodology best suits their needs.

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Acknowledgements

Dr. Dougherty gratefully acknowledges support from the William and Marguerite Wurzbach Distinguished Professorship. We thank Michael A. Dawes, M.D. (Psychiatry Department, The University of Texas Health Science Center at San Antonio), for his review and editorial contributions to this manuscript, as well as Karen Klein, MA, ELS (Research Support Core, Wake Forest University Health Sciences), for her editorial contributions.

While the authors Dougherty, Marsh-Richard, Mathias, and Addicott were affiliated with The University of Texas Health Science Center at Houston during the data collection for this study, Drs. Dougherty, Marsh-Richard, and Mathias have since relocated to The University of Texas Health Science Center at San Antonio. Ms. Addicott has relocated to the Wake Forest University School of Medicine.

Disclosure/conflict of interest statement

There are no conflicts of interest to report for any of the authors of this manuscript. This study was conducted in compliance with the Declaration of Helsinki and the current laws of the USA.

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Authors and Affiliations

  1. Neurobehavioral Research Laboratory and Clinic, Department of Psychiatry, School of Medicine, The University of Texas Health Science Center at San Antonio, Mail Code 7793, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA

    Donald M. Dougherty, Dawn M. Marsh-Richard & Charles W. Mathias

  2. Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Ashley J. Hood

  3. Neuroscience Program, Wake Forest University Health Sciences, Winston-Salem, NC, USA

    Merideth A. Addicott

  4. Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    F. Gerard Moeller

  5. Department of Medical Biochemistry, University Hospital of Wales, Cardiff, Wales, UK

    Christopher J. Morgan

  6. The Cardiff School of Health Sciences, University of Wales Institute Cardiff, Cardiff, Wales, UK

    Abdulla A.-B. Badawy

Authors
  1. Donald M. Dougherty
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  2. Dawn M. Marsh-Richard
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  3. Charles W. Mathias
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  4. Ashley J. Hood
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  5. Merideth A. Addicott
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  6. F. Gerard Moeller
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  7. Christopher J. Morgan
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  8. Abdulla A.-B. Badawy
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Corresponding author

Correspondence to Donald M. Dougherty.

Additional information

This research was sponsored by grants from the National Institutes of Health (R01-AA012046, R01-AA014988, and T32-AA07565) and a Wellcome Trust grant.

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Dougherty, D.M., Marsh-Richard, D.M., Mathias, C.W. et al. Comparison of 50- and 100-g l-tryptophan depletion and loading formulations for altering 5-HT synthesis: pharmacokinetics, side effects, and mood states. Psychopharmacology 198, 431–445 (2008). https://doi.org/10.1007/s00213-008-1163-2

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  • DOI: https://doi.org/10.1007/s00213-008-1163-2

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