A new study published in Communications Biology sheds light on how the psychedelic compound DMT changes the brain’s dynamic behavior. Researchers found that DMT reduces the amount of energy the brain needs to switch between different activity states. This reduction in control energy was linked to increased complexity in brain signals and to how intense the psychedelic experience felt to participants. The effects were strongest in brain regions rich in serotonin 2a receptors, which are known to play a key role in the effects of psychedelics.
DMT, or N,N-dimethyltryptamine, is a powerful psychedelic substance that produces vivid hallucinations and immersive altered states of consciousness. It is found in some plants and is the main psychoactive ingredient in ayahuasca, a ceremonial brew used in some South American spiritual traditions. Unlike other psychedelics like LSD or psilocybin, DMT has a very short duration of action—when injected, its effects come on rapidly and subside within about 20 minutes. This brief but intense experience makes DMT uniquely suited for studies using brain imaging tools like fMRI, which can capture the entire altered state in a single session.
In the current study, researchers sought to understand how DMT changes the way the brain shifts between different states of activity. They were particularly interested in how these changes relate to the serotonin 2a receptor. Previous work has shown that psychedelics like LSD and psilocybin increase the brain’s signal diversity—a measure of how complex and varied brain activity is over time. But this study went further, using a mathematical framework known as network control theory to examine how much effort, or “control energy,” the brain needs to transition from one state to another during the DMT experience.
“I’ve always been interested in studying the brain during non-ordinary states of consciousness and DMT’s rapid onset and metabolism provides a powerful approach to do so,” said study author S. Parker Singleton, a postdoctoral fellow at the Penn Lifespan Informatics & Neuroimaging Center (PennLINC) at the Perelman School of Medicine at University of Pennsylvania.
The study involved 20 participants, 14 of whom were included in the final analysis after removing those with excessive head movement. Each participant underwent two sessions, spaced two weeks apart. In one session, they were given an intravenous injection of DMT; in the other, they received a saline placebo. Functional MRI and EEG recordings were taken during each 28-minute scan. DMT or placebo was injected eight minutes into the scan. In a separate session, participants also rated how intense the drug experience felt every minute on a scale from 0 to 10.
The researchers used network control theory to analyze how much energy was needed for the brain to move from one activity pattern to the next at each time point. They found that DMT consistently lowered this control energy compared to placebo. This suggests that under DMT, the brain more easily transitions between different activity states. This flexibility was not random—it followed a pattern tied to the structure and chemistry of the brain.
“Do you ever wonder what’s going on in the brain when someone is on DMT? Well, so do we,” Singleton told PsyPost. “There’s a lot happening and we’re still working to understand what it all means.”
Importantly, the drop in control energy was linked to two key aspects of the psychedelic experience. First, EEG recordings showed that brain signals became more complex under DMT, an effect known as increased signal diversity. This complexity has been proposed as a marker of expanded conscious experience. Second, the participants’ own reports of how intense the DMT experience felt were inversely related to control energy—lower energy requirements were associated with stronger subjective effects.
These relationships varied across different parts of the brain. When the researchers looked at specific brain networks, they found that control energy dropped most significantly in the visual system, the frontoparietal network, and the default mode network. These networks are often implicated in visual processing, attention, and self-referential thought, and they have been shown in previous studies to be particularly affected by psychedelics. Interestingly, the timing of these effects differed: the frontoparietal and default mode networks showed the greatest changes early in the experience, while the visual network’s changes were more sustained and appeared later.
“We found what I believe to be a pretty convincing arousal (vigilance) effect in the visual cortex during the later stages of the scan,” Singleton said. “We likely would not have caught this without our time-resolved approach.”
At an even finer level, the researchers looked at individual brain regions to see how changes in control energy corresponded to the local density of serotonin 2a receptors. They used brain maps from previous PET imaging studies to estimate how many of these receptors were present in each region. They found that areas with higher serotonin 2a receptor density tended to show larger drops in control energy during the DMT session. These same regions also showed stronger associations between control energy and both EEG signal diversity and subjective intensity.
To ensure that this connection wasn’t just a coincidence, the researchers ran a dominance analysis comparing several types of serotonin receptors. The serotonin 2a receptor consistently emerged as the most important predictor of how DMT affected brain control energy. This reinforces the idea that DMT’s effects are specifically tied to its action on this particular receptor.
Taking the analysis a step further, the team asked whether they could simulate DMT’s effects on brain control energy using only placebo data, receptor maps, and pharmacological modeling. They built a simulation that estimated DMT’s concentration in the brain over time and scaled this by serotonin 2a receptor density across brain regions. Using this model as a guide for where and when DMT would act, they were able to recreate the observed changes in control energy with high accuracy. This approach could open new avenues for predicting how other compounds might affect brain dynamics based on their pharmacological profiles.
The study offers a detailed picture of how DMT temporarily shifts the brain into a more fluid and flexible mode of functioning. By requiring less control energy to move between different activity patterns, the brain may be able to explore a broader range of mental states, contributing to the intense and sometimes transformative nature of the psychedelic experience. The close alignment of these changes with serotonin 2a receptor distribution also strengthens the case that this receptor is a key gateway for the altered states produced by psychedelics.
Despite its insights, the study has limitations. The sample size was relatively small, and individual differences in brain structure were not accounted for, since the researchers used a group-average structural connectome. The design was single-blind rather than double-blind, which might introduce some bias. Also, while the researchers found strong associations at the group level, future studies could explore whether these patterns hold true at the individual level—an important step for personalizing psychedelic therapy.
“We still have a lot to learn about psychedelic action in the brain,” Singleton said. “On-going work seeks to address many potential confounds including influences of arousal, head motion, and these drugs’ ability to impact the tone of blood vessels.”
The study, “Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience,” was authored by S. Parker Singleton, Christopher Timmermann, Andrea I. Luppi, Emma Eckernäs, Leor Roseman, Robin L. Carhart-Harris, and Amy Kuceyeski.
