Effect of glucose on tobacco craving. Is it mediated by tryptophan and serotonin?

Psychopharmacology (Berl). 2005 Feb;178(1):27-34. doi: 10.1007/s00213-004-1980-x. Epub 2004 Jul 31.


Rationale: Oral glucose has been shown to decrease tobacco craving in many but not all previous studies. Glucose ingestion may facilitates entry of tryptophan (TRP), the unique source of brain serotonin, into the brain, glucose's action seems to be opposite of rapid TRP depletion. Therefore, the aim was to assess the effect of high doses of oral glucose on tobacco craving, withdrawal symptoms, plasma TRP and blood serotonin concentrations in temporarily abstinent smokers.

Methods: Aspartame 0.6 g/200 ml (A, placebo), glucose 32.5 g/200 ml (G32.5) and 75 g/200 ml water (G75) were administered to 12 healthy smokers after an overnight abstinence in a crossover, double blind study. Tobacco craving (short version of the Tobacco Craving Questionnaire, TCQ), withdrawal symptoms, choice reaction time, affect, blood glucose, plasma insulin, nicotine, cotinine, free and total TRP, and blood serotonin concentrations were assessed during a period of 5 h after administration.

Results: Blood glucose and plasma insulin increased after G32.5, G75 and remained unchanged after A. TCQ score increased with A and remained almost unchanged with both doses of glucose (conditionxtime interaction: P=0.023). Total withdrawal score increased differently according to sex and condition (P<0.05). Motor reaction time increased with A and decreased with glucose (P=0.016). The overall decrease in plasma TRP was 0.31+/-17, 0.49+/-0.19 and 1.44+/-0.24 mg/l with A, G32.5 and G75, respectively (P<0.001). Baseline blood serotonin was lower in women (n=5) than in men; it showed a condition by time (P=0.007) and a condition by time by sex interaction (P=0.023).

Conclusions: Glucose attenuates tobacco craving and withdrawal symptoms in temporarily abstinent smokers. This is accompanied by a decrease in plasma TRP and a sex dependent increase in blood serotonin. Further studies assessing the direct effect of glucose on brain serotonin are needed to ascertain whether a glucose induced reduction in craving is associated with an increase in brain serotonin.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Affect / drug effects
  • Behavior, Addictive / drug therapy
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glucose / administration & dosage
  • Glucose / pharmacology*
  • Humans
  • Male
  • Reaction Time / drug effects
  • Serotonin / blood*
  • Substance Withdrawal Syndrome / blood*
  • Substance Withdrawal Syndrome / physiopathology
  • Tobacco Use Disorder / blood*
  • Tobacco Use Disorder / physiopathology
  • Tryptophan / blood*


  • Serotonin
  • Tryptophan
  • Glucose