Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals

Psychopharmacology (Berl). 2002 Dec;164(4):385-91. doi: 10.1007/s00213-002-1238-4. Epub 2002 Oct 12.


Rationale: Reduced serotonergic activity has been associated with impulsive behavior; however, intervention studies have been scarce.

Objectives: To examine whether induced lowering of serotonin (5-HT) levels would increase behavioral measures of impulsivity.

Methods: Twenty-four healthy young males ingested a mixture of the essential amino acids except for tryptophan in a balanced, randomized, double-blind, placebo-controlled, cross-over study design. The continuous-performance test-identical pairs was administered when the plasma concentration of tryptophan was expected to be at the lowest point. The plasma concentrations of 23 amino acids were measured at baseline and 5 h after the ingestion of the amino acid mixture.

Results: The intervention led to a dramatic fall in free and total plasma tryptophan, and the tryptophan/large neutral amino acids ratio. This in turn has been shown to lower the level of 5-HT in the central nervous system. The tryptophan depletion resulted in a statistically significant more impulsive- or disinhibited response style on the continuous-performance test-identical pairs when the subjects were solving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer correct responses and a decreased ability to discriminate between stimuli.

Conclusions: These results indicate that a rapid lowering of tryptophan increases impulsiveness and decreases discriminating ability in normal individuals. The effect of 5-HT depletion on discriminating ability in this study was similar to that previously reported in depressed patients.

Publication types

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

MeSH terms

  • Adult
  • Attention / physiology
  • Cross-Over Studies
  • Discrimination Learning / physiology
  • Double-Blind Method
  • Humans
  • Impulsive Behavior / physiopathology*
  • Impulsive Behavior / psychology
  • Male
  • Neuropsychological Tests
  • Problem Solving / physiology
  • Serotonin / deficiency
  • Serotonin / physiology*
  • Tryptophan / blood
  • Tryptophan / deficiency*


  • Serotonin
  • Tryptophan