Psychoactive substances 25H-NBOMe and 25H-NBOH induce antidepressant-like behavior in male rats.

Synthetic psychedelics 25H-NBOMe and 25H-NBOH, which act on serotonin 5-HT2A receptors, reduced depressive-like behavior in male adult rats. In the forced swimming test, both substances produced significantly greater motivation to escape compared to controls, suggesting antidepressant properties. All doses (0.1, 1, and 3 mg/kg) caused hallucinogenic effects as measured by head twitch responses. Locomotor activity in the open field test was unaffected except at the highest dose (3 mg/kg), which reduced movement. These findings indicate that a single dose of these compounds may have antidepressant potential, contributing to psychedelic research for psychiatric treatments.

Study at a glance

Abstract

Ring-substituted phenethylamines are believed to induce psychedelic effects primarily by interacting with 5-hydroxytryptamine 2 (5-HT2A) receptors in the brain. We assessed the effect of the psychedelic substances 25H-NBOMe and 25H-NBOH on the depressive-like behavior of male adult rats. Naive Wistar rats were divided into groups to assess the effects of different doses (0.1 mg/kg, 1 mg/kg, and 3 mg/kg) of 25H-NBOMe and 25H-NBOH. The substances were administered intraperitoneally and the hallucinogenic properties were evaluated using the head twitch response test (HTR). Additionally, we assessed their locomotor activity in the open field test (OFT) and depressive-like behavior in the forced swimming test (FST). Our data demonstrated that all doses of synthetic psychedelic substances evaluated exhibited hallucinogenic effects. Interestingly, we observed that both 25H-NBOMe and 25H-NBOH produced a significantly greater motivation to escape in the FST, compared to the control group. Furthermore, we found no significant differences in locomotor activity during the OFT, except for the dose of 3 mg/kg, which induced a reduction in locomotion. This study provides new insights into a potential psychedelic substance, specifically by demonstrating the previously unknown antidepressant properties of a single dose of both 25H-NBOMe and 25H-NBOH. These findings contribute to the ongoing progress of experimental psychiatry toward developing safe and effective clinical practices in the field of psychedelics research.