Influence of cigarette smoking on melatonin levels in man

Eur J Clin Pharmacol. 2005 May;61(3):197-201. doi: 10.1007/s00228-005-0908-7. Epub 2005 Apr 12.


Objective: Polycyclic aromatic hydrocarbons in cigarette smoke induce cytochrome P450(CYP)1A2, which is involved in the hepatic metabolism of melatonin (MT). This suggests that habitual smokers may have low serum MT levels during smoking compared with a non-smoking period. We decided to investigate whether this suggestion is correct.

Methods: Eight habitual smokers were tested on two occasions. They had smoked prior to the first occasion but had not smoked for 7 days prior to the second. Each test was divided into two parts. The first part spanned the night between 2000 hours and 0800 hours. Venous blood samples were collected every second hour during this period for analysis of endogenous serum MT. The second part was performed the subsequent day. At 0930 hours, 25 mg MT was ingested orally, and blood samples for exogenous serum MT analysis were collected every hour between 1000 hours and 1600 hours. Endogenous and exogenous areas under the serum MT-time curve (MT-AUCs) were calculated.

Results: Endogenous serum MT-AUCs were similar during the two periods. Oral administration of MT induced supraphysiological levels of serum MT. Moreover, exogenous serum MT-AUCs were significantly smaller before than after smoking abstinence (7.34+/-1.85 versus 21.07+/-7.28 nmol/lxh; P<0.02; means+/-SEM).

Conclusion: This investigation shows that exogenous, but not endogenous (at night), serum MT levels are influenced by cigarette smoking. When the MT levels are low, the influence of CYP1A2 levels appears to be less pronounced than when they are high, and the enzyme capacity hugely utilized. These findings implicate that interactions between exogenous MT, and substrates metabolized by CYP1A2, may differ in individuals before and after smoking abstinence.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacokinetics
  • Area Under Curve
  • Circadian Rhythm
  • Cotinine / blood
  • Female
  • Humans
  • Male
  • Melatonin / administration & dosage
  • Melatonin / blood
  • Melatonin / pharmacokinetics*
  • Smoking / physiopathology*
  • Smoking Cessation


  • Antioxidants
  • Melatonin
  • Cotinine