Intravenous DMT administered as a 30-second bolus followed by a 6-hour infusion, reaching peak blood concentrations around 35 ng/mL, is safe in healthy volunteers. No serious adverse events occurred; all side effects were mild and self-limiting. Vital signs, electrocardiography, and measures of suicidality or psychopathology showed no significant abnormalities. Mild psychedelic effects were accompanied by temporary decreases in sustained attention, postural stability, and occipital alpha brain wave power at the highest dose. Moderate variability in drug levels between individuals was observed. These findings support further testing of prolonged DMT infusion as a potential treatment to promote neuroplasticity in stroke recovery.
Esketamine nasal spray is the first glutamate-modulating antidepressant approved as a monotherapy for adults with treatment-resistant depression. It acts rapidly by blocking NMDA receptors on inhibitory interneurons, which disinhibits glutamate release and alters synaptic plasticity. Administered at 56 mg or 84 mg, it reaches peak concentration in 20–40 minutes with about 50% bioavailability. This review covers its regulatory approval, mechanism of action, pharmacokinetics, and clinical trial data for efficacy and safety in treatment-resistant depression and major depressive disorder with acute suicidal ideation or behavior.