Research Spotlight: Nicolas Glynos, PhD – Associate Pharmacometrician

A Rapid-Acting Psychedelic, Studied in Context

N,N-Dimethyltryptamine (DMT) is a fast-acting serotonergic psychedelic being investigated for its potential in psychiatric disorders and for what it can teach us about consciousness. As interest in psychedelics grow, a key challenge is bridging the gap between mechanistic understanding and clinically meaningful outcomes. At A2-Ai, we specialize in translating potential novel mechanisms of action (MOA) into real patient outcomes. We do this by mapping and quantifying these unique MOA and biological measurements, such as those of DMT, and strategically assessing and reviewing them every step of the way to safely and effectively bring solutions to patients who need them.

In a recent publication in The Journal of Neuroscience, Associate Pharmacometrician, Nicolas Glynos, PhD, et. al, presents one of the most comprehensive studies of intravenous DMT conducted in rodents: “Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N-Dimethyltryptamine in Rats”. With the goal of linking drug exposure to brain function, the authors examined how DMT relates to measurable changes in behavior, cortical neurochemistry, and brain-wide electroencephalographic (EEG) dynamics within the same experimental framework.

A Study Designed to Link Multiple Signals

DMT was administered intravenously to rats at low, medium, and high doses, allowing tight control over dosing, timing, and exposure. From there, the authors collected three complementary readouts:

Dose-Dependent Increases in Serotonin and Dopamine

DMT produced dose-dependent increases in both serotonin and dopamine in the medial prefrontal and somatosensory cortices. The magnitude of these increases correlated with measured DMT concentrations in the brain, supporting an exposure-response relationship at the level of monoamine signaling. In contrast, many other analytes did not change during peak exposure, including glutamate, which is often discussed in broader models of psychedelic mechanisms. Findings like this can help clarify which neurochemical changes may be most practical to prioritize in human studies.

DMT Reshapes Brain Rhythms and Connectivity

DMT also produced a clear shift in cortical EEG patterns: theta power decreased, while delta and gamma power increased. Gamma-band functional connectivity also strengthened, with greater synchronization across specific electrode pairings, including frontal-parietal connections. Together, these findings indicate that DMT reorganizes large-scale network communication in a dose-dependent manner.

Endogenous DMT in the Cortex

In addition to the expected behavioral effects, such as the DMT-induced head twitch response, the authors also reported that DMT was detectable in the cortex under baseline conditions at levels comparable to serotonin and dopamine. This confirmed previous reports that DMT is present endogenously in the mammalian brain, raising questions about a potential endogenous physiological role beyond its pharmacological effects.

Why This Matters

Dr. Glynos’s work provides a structured way to interpret DMT’s effects at molecular, systems, and behavior levels within the same experimental design, clarifying which findings correspond with exposure and scale with dose. This kind of cross-level evaluation is central to how A2-Ai approaches complex datasets across drug programs. It also helps point to measurable endpoints that can be translated to human studies.

Read the Full Article Here: https://www.jneurosci.org/content/46/5/e0742242025