European Journal of Clinical Pharmacology

, Volume 64, Issue 1, pp 1–8 | Cite as

Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: relation with serotonin levels

  • Cristiana Rossi
  • Luigi Alberto Pini
  • Maria Letizia Cupini
  • Paolo Calabresi
  • Paola Sarchielli
Clinical Trial



Chronic migraine (CM) and medication-overuse headaches (MOH) are well-recognized disabling conditions affecting a significant portion of the headache population attending centers specialized in treating headaches. A dysfunctioning of the serotonergic system has been demonstrated in MOH and CM patients. Here we report on our assessment of the dysfunctioning of the endocannabinoid system as a potential underlying factor in pathogenic mechanisms involved in CM and MOH.


To test the hypothesis of an impairment in the endocannabinoid system in patients with MOH and CM and to assess its relationship with any disruption of the serotonergic system, we determined the levels of the two main endogenous cannabinoids, anandamide (AEA) and 2-acylglycerol (2-AG), in platelets of 20 CM patients, 20 MOH patients and 20 control subjects and also measured the platelet serotonin levels in the same patients.


We found that 2-AG and AEA levels were significantly lower in MOH patients and CM patients than in the control subjects, without significant differences between the two patient groups. Serotonin levels were also strongly reduced in the two patient groups and were correlated with 2-AG levels, with higher values for MOH patients.


These data support the potential involvement of a dysfunctioning of the endocannabinoid and serotonergic systems in the pathology of CM and MOH. These systems appear to be mutually related and able to contribute to the chronification of both CM and MOH.


Chronic headache Endocannabinoids Medication-overuse headache Serotonin 



This study has been partially supported by the Lega Italiana Cefalalgici. The authors express their gratitude to John A. Toomey for editing the English and Marisa M. Morson for technical assistance.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Cristiana Rossi
    • 1
  • Luigi Alberto Pini
    • 2
  • Maria Letizia Cupini
    • 3
  • Paolo Calabresi
    • 1
    • 4
  • Paola Sarchielli
    • 1
    • 5
  1. 1.Neurologic Clinic, Department of Medical and Surgical Specialties and Public HealthUniversity of PerugiaPerugiaItaly
  2. 2.Institute of Clinical PharmacologyUniversity of ModenaModenaItaly
  3. 3.U.O.C. Neurologia, Dipartimento Cranio SpinaleOspedale S. EugenioRomeItaly
  4. 4.IRCCS Fondazione S. LuciaRomeItaly
  5. 5.Neurologic ClinicOspedale Santa Maria della MisericordiaSan Sisto-PerugiaItaly

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