Tryptophan depletion in normal volunteers produces selective impairments in learning and memory

Neuropharmacology. Mar-Apr 1994;33(3-4):575-88. doi: 10.1016/0028-3908(94)90089-2.


The amino-acid L-tryptophan is essential in the synthesis of brain serotonin, and its depletion can lead to a widespread reduction in central serotonergic activity. A placebo-controlled cross-over within-subjects design (n = 12) examined the effects of tryptophan depletion on human cognitive performance. A low-tryptophan (low-TRP) drink successfully reduced the levels of plasma and total free tryptophan. Computerized tests of memory, learning and executive function revealed selective and non-sedative impairments on cognitive performance following the active drink. Specifically, low-TRP impaired learning as seen in tests of visual discrimination and paired associates. Furthermore, low-TRP lengthened thinking times during the Tower of London planning task, but only in subjects already familiar with the task, suggesting a retrieval deficit. No evidence was found for an effect of the low-TRP drink on measures sensitive to frontal lobe dysfunction, supporting instead a specific role for the serotonergic system in the processes of memory and learning not directly implicated in frontal lobe function.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acids / blood
  • Amino Acids / pharmacology
  • Brain Chemistry / drug effects
  • Cognition / drug effects
  • Cross-Over Studies
  • Discrimination, Psychological / drug effects
  • Humans
  • Learning Disabilities / metabolism*
  • Learning Disabilities / psychology
  • Male
  • Memory Disorders / metabolism*
  • Memory Disorders / psychology
  • Mental Processes / drug effects
  • Neuropsychological Tests
  • Pattern Recognition, Visual / drug effects
  • Space Perception / drug effects
  • Tryptophan / deficiency*


  • Amino Acids
  • Tryptophan