Endogenous cannabinoids in patients with schizophrenia and substance use disorder during quetiapine therapy

J Psychopharmacol. 2008 May;22(3):262-9. doi: 10.1177/0269881107083816.


Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Arachidonic Acids / blood
  • Cannabinoid Receptor Modulators / blood*
  • Chromatography, High Pressure Liquid
  • Diagnosis, Dual (Psychiatry)
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / therapeutic use*
  • Endocannabinoids
  • Female
  • Humans
  • Linear Models
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Polyunsaturated Alkamides / blood
  • Psychiatric Status Rating Scales
  • Quetiapine Fumarate
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology
  • Substance-Related Disorders / blood*
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / psychology


  • Antipsychotic Agents
  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Dibenzothiazepines
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Quetiapine Fumarate
  • anandamide