Aim: To test the hypothesis that schizophrenia might be associated with alterations of the endogenous cannabinoid system in human blood.Results: Blood from 20 healthy volunteers and 12 patients with schizophrenia, 5 of which both before and after a successful antipsychotic treatment, was analysed for: 1) the amounts of the endocannabinoid anandamide; 2) the levels of cannabinoid CB 1 and CB 2 receptor mRNAs, and 3) the levels of the mRNA encoding the enzyme fatty acid amide hydrolase (FAAH), responsible for anandamide degradation.The amounts of anandamide were significantly higher in the blood of patients with acute schizophrenia than in healthy volunteers (7.79 ± 0.50 vs. 2.58 ± 0.28 pmol/ml). Clinical remission was accompanied by a significant decrease of the levels of anandamide (3.88 ± 0.72 pmol/ml) and of the mRNA transcripts for CB 2 receptors and FAAH. Conclusion:These findings indicate that endocannabinoid signalling might be altered during the acute phase of schizophrenia not only in the central nervous system but also in the blood. These changes might be related to the several immunological alterations described in schizophrenia.

Firm conclusions to explain these results cannot be drawn. However, a hypothetical involvement of the serotonergic system, suggested by the excess of OCD in the pedigree, seems supported by the response of these two individuals to fluoxetine. It may be worth further exploring the value of the psychiatric picture in selecting the appropriate treatment for at least some cases of HD.