Recent research published in communication biology The findings suggest that powerful hallucinogens can induce a unique brain state in which awake, moving animals exhibit brain waves typically associated with deep sleep. This unusual combination of sleep and wake characteristics provides evidence that psychedelic drugs may temporarily reorganize brain activity in a way that promotes learning and emotional recovery.
The substance at the center of this study is 5-MeO-DMT, a fast-acting psychedelic compound known for inducing intense dream-like experiences and altered perceptions of reality. Scientists are currently studying this substance as a potential treatment for mental health conditions such as severe depression and anxiety.
The new research was led by Benjamin Breantander as part of his PhD in the Department of Physiology, Anatomy and Genetics at the University of Oxford, under the supervision of Professor Vladislav Vyazovsky. Benjamin is currently a postdoctoral researcher at the Paris School of Physics and Industrial Chemistry.
Scientists initially wanted to understand how psychedelics interact with the body’s natural rest cycles, since severe depression tends to greatly disrupt normal sleep patterns. They designed this study to see what sleep looks like after the immediate effects of 5-MeO-DMT wear off.
“When we started developing this project, the main impetus for psychedelic research was the potential therapeutic properties of psychedelics for treatment-resistant depression. However, in this type of pathology, sleep is greatly affected. Despite this, there were no publications reporting the effects of psychedelics on sleep,” Breander and Vyazovsky told SciPost.
As the project progressed, researchers realized that the drug’s immediate effects during wakefulness raised many unexpected questions. They decided to look at the exact brain states caused by the drug to see if they could explain the substance’s therapeutic effects.
To investigate these effects, the scientists conducted a series of experiments using 42 adult male mice. They surgically implanted small sensors into the animals’ brains to record brainwave activity, which measures electrical signals produced by nerve cells.
The researchers also built a custom-made small camera device called an ophthalmometer, which they attached securely to the animals’ heads to continuously monitor pupil dilation. They used automated video tracking software to precisely measure the diameter of the pupils of the mice as they moved around. Pupil size is a standard physical indicator of alertness, as pupils commonly dilate when an animal is highly alert and physically excited.
In the main experiment, mice were injected with either 5-MeO-DMT or harmless saline. The scientists then monitored the animals’ brain waves, pupil size, and physical behavior for several hours.
Brain recordings after 5-MeO-DMT injection showed a significant increase in slow wave activity. Slow waves are large, rhythmic electrical pulses that typically occur only during the deep recovery phase of non-rapid eye movement sleep.
During typical deep sleep, slow brain waves are accompanied by brief moments when nerve cells completely stop firing (known as neuron off periods). The researchers found that injections of 5-MeO-DMT caused similar silent-off periods even while the mice were fully awake, providing evidence that the drug was triggering a genuine sleep-like mechanism.
Despite exhibiting brain waves characteristic of deep sleep, the mice were physically awake and actively moving around the enclosure in which they were kept. They engaged in normal wake-up behaviors such as exploring, grooming, and running on exercise wheels.
Camera recordings revealed that the animal’s pupils were dilated widely during this period. The combination of deep sleep brainwaves and high physical arousal indicates a dissociated state in which elements of both sleep and wakefulness are fused.
The researchers also noted that theta waves, a specific brain rhythm normally associated with movement and exploration of the surroundings, disappeared completely. Suppression of these rhythms in actively moving animals suggests that there is a temporal disconnect between physical movement and standard brain activity.
“We found that during the acute phase of psychedelic administration, when behavioral markers are higher, brain activity resembles that of a sleep stage called slow-wave sleep (the eponymous slow-wave is measured in electroencephalographic recordings),” Breander and Vyazovsky told Cypost. “We also measured pupil size as a marker of cortical arousal (which should increase during wakefulness, but decrease during sleep). We found that, paradoxically, pupil size had reached the size classically associated with high levels of arousal. Therefore, in the brain we were faced with a state of alertness with an element of sleep, but our behavior corresponded to a state of wakefulness.”
“All of our results were surprising. Up until now, studies on slow-wave activity have been mainly contained within sleep studies. Our results were truly puzzling: How were our subjects able to show unmistakable signs of arousal in their behavior, even though their brains were filled with signals associated with disconnection from the external environment? Moreover, certain brain rhythms that were associated with movement were completely absent in moving animals.”
To understand the specific chemical pathways involved, scientists conducted additional tests using compounds that block specific serotonin receptors. These receptors act as chemical docking stations in the brain that respond to naturally occurring chemicals and hallucinogens.
When mice received the blocker before 5-MeO-DMT, the psychedelic drug no longer caused pupil dilation or suppression of theta waves. Slow-wave activity in the brain actually increases, suggesting that completely different chemical networks control different aspects of the psychedelic experience.
The researchers also tried injecting psychedelic compounds directly into specific areas of the outer layer of the brain using small tubes. This local injection did not cause the large-scale behavioral or brain wave changes that systemic injections did.
This local test shows that unique wake-sleep states depend on extensive global brain networks. They tend to require activation of the entire brain, rather than just a single isolated area.
To test motivation and natural behavior, scientists gave several mice a bowl of sugar pellets. Mice given the psychedelic compound took much longer to approach and eat the treat.
Instead of eating, the animals shifted their focus to grooming and exploring bedding. This behavioral change provides evidence that the drug reduces reward-driven activity and changes the animal’s immediate priorities.
In another phase of the study, the scientists used novel objects to keep groups of mice awake for four hours to increase their biological need for sleep. Usually this kind of sleep deprivation leads to a strong rebound in slow waves when the animal finally rests.
When the scientists administered 5-MeO-DMT immediately after this period of sleep deprivation, the expected rebound of sleep slow waves was significantly reduced. This suggests that drug-induced slow waves may partially satisfy the brain’s biological need for deep sleep.
The research team also tracked the mice’s long-term sleep patterns over a 48-hour period. Although rapid eye movement sleep was initially suppressed by the drug, the animals experienced delayed overcompensation.
Over the next two days, they spent much more time in this dreamy sleep stage. Rapid eye movement sleep is essential for processing emotional memories, meaning this delayed rebound may play a role in the drug’s therapeutic potential.
“This effect opens up the possibility of understanding the long-term effects of psychedelics through the lens of sleep research,” the researchers explained. “The literature on slow waves suggests that slow waves may influence plasticity, and the conditions in which global slow waves exist, as we are reporting, may be a medium that supports global brain changes, but that is still speculation on our part.”
“We could take that idea further. Slow waves are commonly associated with a feeling of disconnection from the environment, and one might wonder if they could be the basis of psychedelic experiences. Our results have already been successfully replicated in humans, as shown by research by George Blackburn at UCL.”
Although these findings provide new insights, the scientists note that drug-induced slow waves cannot be classified as true sleep waves. The amplitude of the electrical signals was smaller than natural sleep waves, and the fast brain waves typical of normal wakefulness were still present in the background.
There is a danger of misinterpreting this state as an exact substitute for natural rest. Researchers suggest that the drug may create a unique hybrid state that temporarily disconnects the brain from its external environment.
“In the early stages of sleep research, sleep was subdivided into stages that are still meaningful today,” the researchers said. “One stage in particular was very puzzling. French neuroscientist Michel Jouvet called this state ‘paradoxical sleep’ (called REM sleep in labs outside France) to explain the strange coexistence of awake brain states in the deepest stages of sleep. Reflecting this, we observed the ‘sleeping’ brains of apparently awake animals. Rather than call our findings a psychedelic state, we wanted to… We named it “Paradoxical Wake” in honor of the pioneering work in sleep research in the 1950s.”
Future studies should investigate whether this unique brain condition directly causes the long-term improvements in brain plasticity seen in human clinical trials. Plasticity refers to the brain’s ability to reorganize itself by forming new neural connections, which is essential for recovery from mental illness.
The study, “Dissociation of vigilance induced by 5-MeO-DMT in mice,” was authored by Benjamin JB Bréant, José Prius Mengual, Alexander Andrews, Anna Hoerder-Suabedissen, Jasmin Patel, David M. Bannerman, Trevor Sharp, and Vladyslav V. Vyazovskiy.
