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Background: Depression is a psychiatric disorder with limited therapy options. Psychedelics are new antidepressant candidates, being the ayahuasca one of the most promising ones. A synergistic combination of N,N -dimethyltryptamine (DMT) and β-carbolines allows ayahuasca antidepressant properties. Another psychedelic and DMT-containing beverage is the jurema wine used religiously by indigenous people from Northeastern Brazil., Aims: To evaluate the antidepressant-like effect of standardized extract of Mimosa tenuiflora (SEMT), associated or not with harmine (β-carboline), in behavioral models of depression., Methods: The SEMT was submitted to (+) ESI-IT-LC/MS analysis for DMT quantification. To assess the antidepressant-like effect of SEMT, the open field (OFT), tail suspension (TST), and forced swim (FST) tests were performed. To verify the participation of serotonergic systems, the 5-hydroxytryptophan (5-HTP)-induced head twitch test was performed., Results: The content of DMT found in SEMT was 24.74 ± 0.8 mg/g. Yuremamine was also identified. SEMT presented an antidepressant-like effect in mice submitted to the TST and FST, independent from harmine, with no significant alterations on the OFT. The sub-dose interaction between SEMT and ketamine also produced an anti-immobility effect in the TST, with no changes in the OFT. SEMT potentiated the head twitch behavior induced by 5-HTP and ketanserin prevented its antidepressant-like effect in the TST ( p  < 0.05)., Conclusions: SEMT presented a harmine-independent antidepressant-like effect in mice submitted to the TST and FST. This effect occurs possibly via activation of serotonergic systems, particularly the 5-HT 2A/2C receptors.