Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
Department of Clinical Sciences and Applied Biotechnology, University of L'Aquila, L'Aquila, Italy.
Hum Psychopharmacol. 2021 Jul;36(4):e2779. doi: 10.1002/hup.2779. Epub 2021 Feb 9.
Endocannabinoids have been implicated in the pathophysiology of Major Depressive Disorder (MDD) and might represent potential targets for therapeutic intervention. Objectives of the study were: (1) to measure plasma levels of endocannabinoids in a group of antidepressant-free depressed outpatients; (2) to explore their relationship with the severity of depressive symptoms as subjectively perceived by the patients; and (3) to investigate the effect of the selective serotonin reuptake inhibitor escitalopram on endocannabinoid levels.
We measured plasma levels of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anadamide), in 12 drug-free outpatients diagnosed with MDD and in 12 matched healthy controls. In the patient group, endocannabinoids plasma levels were assessed at baseline and after 2 months of treatment with escitalopram.
Baseline plasma levels of the two endocannabinoids did not differ between depressed patients and healthy controls. However, there was a significant inverse correlation between 2-arachidonoylglycerol levels and the severity of subjectively perceived depressive symptoms. Treatment with escitalopram did not change endocannabinoid levels in depressed patients, although it caused the expected improvement of depressive symptoms.
Our results suggest that 2-arachidonylglycerol, the most abundant endocannabinoid in the central nervous system, might act to mitigate depressive symptoms, and raise the interesting possibility that 2-arachidonylglycerol and anandamide are differentially regulated in patients affected by MDD. Also, our data suggest but do not prove that the endocannabinoid system is not regulated by serotonergic transmission, at least in depressed patients.
内源性大麻素与重性抑郁障碍（MDD）的病理生理学有关，可能代表治疗干预的潜在靶点。本研究的目的是：（1）测量一组未服用抗抑郁药的抑郁门诊患者的血浆内源性大麻素水平；（2）探讨其与患者主观感知的抑郁症状严重程度的关系；（3）研究选择性 5-羟色胺再摄取抑制剂 escitalopram 对内源性大麻素水平的影响。
我们测量了 12 名未服用药物的 MDD 门诊患者和 12 名匹配的健康对照者的两种主要内源性大麻素，即 2-花生四烯酰甘油（2-AG）和 N-花生四烯酰乙醇胺（anadamide）的血浆水平。在患者组中，在基线和 escitalopram 治疗 2 个月后评估内源性大麻素的血浆水平。
基线时，两组患者的两种内源性大麻素血浆水平无差异。然而，2-AG 水平与主观感知的抑郁症状严重程度呈显著负相关。尽管 escitalopram 治疗导致抑郁症状的预期改善，但并未改变抑郁患者的内源性大麻素水平。
我们的结果表明，2-花生四烯酰甘油是中枢神经系统中最丰富的内源性大麻素，可能有助于减轻抑郁症状，并提出了一个有趣的可能性，即 MDD 患者的 2-花生四烯酰甘油和 anandamide 可能受到不同的调节。此外，我们的数据表明，但不能证明内源性大麻素系统不受 5-羟色胺传递的调节，至少在抑郁患者中是这样。
