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Jasmin Obermanns, Hanna Katharina Meiser, Saskia Marie Hoberg, Cynthia Segura Vesterager, Frank Schulz, Georg Juckel, Barbara Emons

• \(\bf Background\) The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention. \(\bf Method\) In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5-HT2A rs6311, and 5-HT1A rs6295 by high-resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) in the blood was measured by liquid chromatography–tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self-questionnaires. Fifty-nine patients participated in a second appointment to measure the concentration of AEA, 2-AG, and symptoms of depression and anxiety. \(\bf Results\) We observed higher AEA and decreased 2-AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2-AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2-AG. Gender differences were found concerning increased 2-AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5-HT1A rs6295 and 5-HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients. \(\bf Conclusion\) In conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2-AG and AEA, and genetic variations of the 5-HT1A and 5-HT2A could play a role in patients with depression and may be involved in a depressive disorder.