, Volume 206, Issue 4, pp 531–549

Role of cannabis and endocannabinoids in the genesis of schizophrenia

  • Emilio Fernandez-Espejo
  • Maria-Paz Viveros
  • Luis Núñez
  • Bart A. Ellenbroek
  • Fernando Rodriguez de Fonseca



Cannabis abuse and endocannabinoids are associated to schizophrenia.


It is important to discern the association between schizophrenia and exogenous Cannabis sativa, on one hand, and the endogenous cannabinoid system, on the other hand.


On one hand, there is substantial evidence that cannabis abuse is a risk factor for psychosis in genetically predisposed people, may lead to a worse outcome of the disease, or it can affect normal brain development during adolescence, increasing the risk for schizophrenia in adulthood. Regarding genetic predisposition, alterations affecting the cannabinoid CNR1 gene could be related to schizophrenia. On the other hand, the endogenous cannabinoid system is altered in schizophrenia (i.e., increased density of cannabinoid CB1 receptor binding in corticolimbic regions, enhanced cerebrospinal fluid anandamide levels), and dysregulation of this system can interact with neurotransmitter systems in such a way that a “cannabinoid hypothesis” can be integrated in the neurobiological hypotheses of schizophrenia. Finally, there is also evidence that some genetic alterations of the CNR1 gene can act as a protectant factor against schizophrenia or can induce a better pharmacological response to atypical antipsychotics.


Cannabis abuse is a risk factor for psychosis in predisposed people, it can affect neurodevelopment during adolescence leading to schizophrenia, and a dysregulation of the endocannabinoid system can participate in schizophrenia. It is also worth noting that some specific cannabinoid alterations can act as neuroprotectant for schizophrenia or can be a psychopharmacogenetic rather than a vulnerability factor.


Cannabis Endocannabinoid Psychosis Schizophrenia Neurobiology Genetic Epidemiology 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Emilio Fernandez-Espejo
    • 1
  • Maria-Paz Viveros
    • 2
  • Luis Núñez
    • 3
  • Bart A. Ellenbroek
    • 4
  • Fernando Rodriguez de Fonseca
    • 5
  1. 1.Departamento de Fisiología Médica, Facultad de MedicinaUniversidad de SevillaSevilleSpain
  2. 2.Departamento de Fisiología (Fisiología Animal II)Universidad Complutense de MadridMadridSpain
  3. 3.Centro MédicoPamplonaSpain
  4. 4.Evotec Neurosciences GmbH, Neuropharmacology, CiMHamburgGermany
  5. 5.Fundación IMABISHosp. Reg. Univ. Carlos HayaMálagaSpain

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