The hallucinogen 25B-NBOMe, which binds strongly to serotonin receptors, increased dopamine, serotonin, and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. It induced hallucinogenic activity, impaired short-term memory as measured by the novel object recognition test, and reduced locomotor activity in the open field test. In the light/dark box, rats spent more time in the dark zone, suggesting an anxiogenic effect. Scopolamine blocked the memory impairment. Unlike MDMA, 25B-NBOMe showed a subtle genotoxic effect in the comet assay. The changes in neurotransmitter levels may stem from its affinity for the 5-HT2A receptor.
The hallucinogenic compound 25I-NBOMe acts through specific serotonin receptors to produce its effects. In rats, blocking the 5-HT2A or 5-HT2C receptors with selective antagonists reduced both the hallucinogenic-like behavior (wet dog shakes) and the release of glutamate, dopamine, and serotonin in the frontal cortex caused by 25I-NBOMe. Blocking the 5-HT1A receptor did not affect the behavior or glutamate release but did decrease dopamine and serotonin release, likely by disinhibiting GABA neurons. These findings indicate that 5-HT2A and 5-HT2C receptors are key mediators of 25I-NBOMe's hallucinogenic activity and its effects on neurotransmitter release in the frontal cortex.