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Background: The unconventional therapeutic methods in psychiatry shed light not only on possible innovative ways of treatment but also a chance of advancement in diagnosing mental disorders. Noteworthy is the pathophysiological basis of endocannabinoid lipid-based endogenous mediators' activity. As the endocannabinoid system (ECS) modulates the action of various neurotransmitters including dopamine, glutamate, and γ-aminobutyric acid, the fact that it can be affected by cannabinoids remains of great importance. The mechanism of action bears the dualistic hallmarks carrying the risk of psychosis through the consumption of delta-9-tetrahydrocannabinol, and on the other hand cannabidiol (CBD) reveals anti-inflammatory and antipsychotic effects. Since both anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are generated from membrane phospholipids that contain arachidonic acid (AA), ECS combines the interaction of dietary lipids and synaptic activity. Studies reporting elevated levels of AEA in blood and cerebrospinal fluid (CSF) predisposes AEA as a potential biomarker of psychosis.
Objective: To demonstrate the multidimensional potential of exploring the ECS in terms of: a) improving the diagnostics of psychotic disorders based on the meaning of AEA, b) understanding the effects of cannabidiol in alleviation of psychotic symptoms, c) searching for the relationship between the diet, nutritional status, and the occurrence of psychotic disorders, d) prevention of disease and/or remission prolongation
Methods: Literature review in PubMed, Google Scholar, and Web of Science using the keywords [psychosis] OR [psychotic] OR [first episode psychosis] OR [schizophrenia] OR [ultra-high risk] OR [UHR] AND [endocannabinoid system] OR [anandamide] OR [AEA] OR [2-arachidonoylglycerol] OR [2-AG] OR [cannabinoids] OR [delta-9-tetrahydrocannabinol] OR [cannabidiol] OR [polyunsaturated fatty acids] OR [PUFA] OR [arachidonic acid] OR [AA]. The review included original articles, reviews, systematic reviews, meta-analyses, and case reports from 1962-2023 in Polish and English.
Results: 68 articles devoted to ECS and psychotic disorders were analyzed. Patients with schizophrenia show increased levels of AEA in whole blood, plasma, and cerebrospinal fluid. This also applies to drug-naïve patients who have experienced first episode psychosis as well as patients during treatment with atypical antipsychotics. There are reports that CBD has potential antipsychotic, anti-inflammatory, antioxidant, anxiolytic and antidepressant properties that have been shown in preliminary clinical trials on individuals with psychotic disorders or at high risk of developing psychosis. ECS It is a major hypothalamic-peripheral system modulator of food intake, nutritional status, energy storage, and adipose tissue influencing body mass status. Loss of ECS proper control might affect either psychosis or anxiety and depression.
Conclusion: The AA as a precursor of endocannabinoid endogenous mediators has a vast impact on ECS' modulation and activity. There are indications of finding links between the AEA level and the risk of developing a psychotic episode. The condition that determines the status of AA as an essential fatty acid exists when there is a deficiency of linoleic acid. Some individuals have no or very limited capacity to convert linoleic acid to AA. Further research on the ECS, nutritional status and the occurrence of psychosis may answer questions that will contribute to improving diagnostics and the use of preventive measures.
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