, Volume 169, Issue 2, pp 186–189 | Cite as

Hypericum perforatum attenuates nicotine withdrawal signs in mice

  • Maria A. Catania
  • Fabio Firenzuoli
  • Anna Crupi
  • Carmen Mannucci
  • Achille P. Caputi
  • Gioacchino CalapaiEmail author
Original Investigation



Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation.


We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice.


Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125–500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs.


The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal.


These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.


Nicotine Withdrawal Abstinence Tobacco Smoking cessation 


  1. Balfour DJ, Redley DL (2000) The effects of nicotine on neural pathways implicated in depression: a factor in nicotine addiction? Pharmacol Biochem Behav 66:79–85Google Scholar
  2. Calapai G, Squadrito F, Rizzo A, Marciano MC, Campo GM, Caputi AP (1995) Multiple actions of the coumarine derivative cloricromene and its protective effects on ischemic brain injury. Naunyn-Schmiedeberg's Arch Pharmacol 351:209–215Google Scholar
  3. Calapai G, Crupi A, Firenzuoli F, Costantino G, Inferreara G, Campo GM, Caputi AP (1999) Effects of Hypericum perforatum on levels of 5-hydroxytryptamine, noradrenaline and dopamine in the cortex, diencephalon and brainstem of the rat. J Pharm Pharmacol 51:723–728PubMedGoogle Scholar
  4. Calapai G, Crupi A, Firenzuoli F, Inferrera G, Ciliberto G, Parisi A, De Sarro G, Caputi AP (2001a) Interleukin-6 involvement in antidepressant action of Hypericum perforatum. Pharmacopsychiatry 34:S8–S10PubMedGoogle Scholar
  5. Calapai G, Crupi A, Firenzuoli F, Inferrera G, Squadrito F, Parisi A, De Sarro G, Caputi AP (2001b) Serotonin, norepinephrine and dopamine involvement in the antidepressant action of Hypericum perforatum. Pharmacopsychiatry 34:45–49PubMedGoogle Scholar
  6. Carton S, Le Houezec J, Lagrue G, Jouvent R (2002) Early emotional disturbances during nicotine patch therapy in subjects with and without a history of depression. J Affect Disord 72:195–199CrossRefPubMedGoogle Scholar
  7. Dierker LC, Avenevoli S, Stolar M, Merikangas KR (2002) Smoking and depression: an examination of mechanisms of comorbidity. Am J Psychiatry 159:947–953CrossRefPubMedGoogle Scholar
  8. Ferry LH (1999) Non-nicotine pharmacotherapy for smoking cessation. Prim Care 26:653–669PubMedGoogle Scholar
  9. Holm KJ, Spencer CM (2000) Bupropion: a review of its use in the management of smoking cessation. Drugs 59:1007–1024PubMedGoogle Scholar
  10. Isola R, Vogelsgerg V, Wemlinger TA, Neff NH, Hafjiconstantinou M (1999) Nicotine abstinence in mouse. Brain Res 850:189–196PubMedGoogle Scholar
  11. Kenny PJ, Markou A (2001) Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav 70:531–549CrossRefPubMedGoogle Scholar
  12. Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349:1436–1442CrossRefPubMedGoogle Scholar
  13. Peters MJ, Morgan LC (2002) The pharmacotherapy of smoking cessation. Med J Aust 176:486–490PubMedGoogle Scholar
  14. Phillipp M, Kohnen R, Hiller K (1999) Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ 319:1534–1538PubMedGoogle Scholar
  15. Quattrocki E, Baird A, Yurgelun-Todd D (2000) Biological aspects of the link between smoking and depression. Harv Rev Psychiatry 8:99–110CrossRefPubMedGoogle Scholar
  16. Rose JE, Behm FM, Westman EC (2001) Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking. Pharmacol Biochem Behav 68:187–197CrossRefPubMedGoogle Scholar
  17. Scarinci IC, Thomas J, Brantley PJ, Jones GN (2002) Examination of the temporal relationship between smoking and major depressive disorder among low-income women in public primary care clinics. Am J Health Promot 16:323–330PubMedGoogle Scholar
  18. Stolerman IP, Jarvis MJ (1995) The scientific case that nicotine is addictive. Psychopharmacology 117:2–10PubMedGoogle Scholar
  19. Sutherland G (2002) Current approaches to the management of smoking cessation. Drugs 62:53–61Google Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Maria A. Catania
    • 1
  • Fabio Firenzuoli
    • 2
  • Anna Crupi
    • 3
  • Carmen Mannucci
    • 1
  • Achille P. Caputi
    • 1
  • Gioacchino Calapai
    • 1
    Email author
  1. 1.Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, School of MedicineUniversity of MessinaMessinaItaly
  2. 2.Service of PhytotherapyOspedale S. GiuseppeEmpoliItaly
  3. 3.Pharmalife-ResearchCalolziocorteItaly

Personalised recommendations