A recent study published in Communications Biology suggests that a powerful psychedelic drug can induce a unique brain state where awake and moving animals exhibit brain waves typically associated with deep sleep. This unusual blend of sleeping and waking characteristics provides evidence that psychedelics may temporarily reorganize brain activity in ways that promote learning and emotional recovery.
The substance at the center of this research is 5-MeO-DMT, a fast-acting psychedelic compound known to produce intense, dream-like experiences and altered perceptions of reality. Scientists are currently exploring this substance as a potential treatment for mental health conditions like severe depression and anxiety.
The new study was led by Benjamin Bréantunder under the supervision of Professor Vladyslav Vyazovskiy as part of his PhD in the Department of Physiology, Anatomy and Genetics at the University of Oxford. Benjamin is now a postdoctoral researcher at the Paris Graduate School of Physics and Industrial Chemistry.
Because severe depression tends to heavily disrupt normal sleep patterns, the scientists initially wanted to understand how psychedelics interact with the body’s natural rest cycles. They designed the study to observe what sleep looks like after the immediate effects of 5-MeO-DMT wear off.
“When we started developing this project, the main drive behind psychedelic research was their potential therapeutic properties against treatment-resistant depression. However, in this type of pathology, sleep is heavily impacted, and yet there was no publication reporting the effects of psychedelics on sleep,” Bréantunder and Vyazovskiy told PsyPost.
As the project progressed, the researchers noticed that the immediate effects of the drug during wakefulness raised many unexpected questions. They decided to observe the exact brain states induced by the drug to see if it might 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 tiny sensors into the animals’ brains to record electroencephalogram activity, which measures the electrical signals produced by nerve cells.
The researchers also built a custom miniature camera device, called an oculometer, which they securely attached to the animals’ heads to continuously monitor pupil dilation. They used automated video tracking software to precisely measure the diameter of the pupils as the mice moved around. Pupil size is a standard physical indicator of alertness, as pupils generally expand when an animal is highly awake and physically aroused.
In the main experiment, the mice received an injection of either 5-MeO-DMT or a harmless saline solution. The scientists then monitored the animals’ brain waves, pupil sizes, and physical behaviors for several hours.
Following the 5-MeO-DMT injection, the brain recordings showed a massive increase in slow-wave activity. Slow waves are large, rhythmic electrical pulses that normally only happen during deep, restorative phases of non-rapid eye movement sleep.
During typical deep sleep, slow brain waves are accompanied by brief moments where nerve cells completely stop firing, known as neuronal OFF-periods. The researchers found that the 5-MeO-DMT injection caused these identical silent OFF-periods to occur even while the mice were completely awake, which provided evidence that the drug was triggering an authentic sleep-like mechanism.
Despite displaying brain waves characteristic of deep sleep, the mice were physically awake and actively moving around their enclosures. They engaged in normal waking behaviors like exploring, grooming, and running on exercise wheels.
The camera recordings revealed that the animals’ pupils were highly dilated during this time. This combination of deep-sleep brain waves and high physical arousal points to a dissociated state that blends elements of both sleeping and waking.
The researchers also noted the complete disappearance of theta waves, which are specific brain rhythms usually linked to movement and exploring one’s environment. The suppression of these rhythms in actively moving animals suggests a temporary disconnect between physical actions and standard brain activity.
“We found that during the acute phase, where the behavioural markers of psychedelic administrations are higher, brain activity is similar to that of a phase of sleep called Slow Wave Sleep (the eponymous slow waves measured electroencephalographic recordings),” Bréantunder and Vyazovskiy told PsyPost. “We also measured pupil size as a marker of cortical arousal (which should be elevated during wakefulness but decreased during sleep), and found that, paradoxically, the pupil size reached a size classically associated with high levels of arousal. So we were faced with a vigilance state with elements of sleep in the brain, while the behaviour corresponds to that of wake.”
“Everything about our results were surprising. So far, the research about slow wave activity was mostly contained within sleep research. Our results were truly puzzling. How could our subjects show undoubtable signs of wakefulness in their behaviour while having a brain full of signals associated with disconnection to the external environment? On top of that, a certain brain rhythm that has been linked to movement was completely gone in animals that were moving.”
To understand the specific chemical pathways involved, the scientists conducted an additional test using a compound that blocks specific serotonin receptors. These receptors act as chemical docking stations in the brain that respond to naturally occurring chemicals and psychedelic drugs.
When the mice received the blocking agent before the 5-MeO-DMT, the psychedelic drug no longer caused pupil dilation or the suppression of theta waves. The slow-wave activity in the brain actually increased, suggesting that completely distinct chemical networks control different aspects of the psychedelic experience.
The researchers also attempted to inject the psychedelic compound directly into a specific region of the brain’s outer layer using tiny tubes. This localized injection did not produce the same massive behavioral or brain wave changes as the whole-body injection.
This localized testing indicates that the unique waking-sleep state relies on widespread, global brain networks. It tends to require the activation of the entire brain rather than just a single isolated region.
To test motivation and natural behavior, the scientists presented some of the mice with a bowl of sugar pellets. After receiving the psychedelic compound, the mice took much longer to approach and eat the treats.
Instead of eating, the animals shifted their focus to grooming and exploring their bedding. This behavioral shift provides evidence that the drug reduces reward-driven activities and alters the animals’ immediate priorities.
In another phase of the study, the scientists kept a group of mice awake for four hours using novel objects to build up their biological need for sleep. Normally, this kind of sleep deprivation leads to a strong rebound of slow waves once the animal finally rests.
When the scientists administered 5-MeO-DMT immediately after this sleep deprivation period, the expected rebound of sleep slow waves was significantly reduced. This suggests that the drug-induced slow waves might partially fulfill the brain’s biological need for deep sleep.
The team also tracked the long-term sleep patterns of the mice over a 48-hour period. While rapid eye movement sleep was initially suppressed by the drug, the animals experienced a delayed overcompensation.
They spent much more time in this dream-heavy sleep phase over the following two days. Rapid eye movement sleep is vital for processing emotional memories, meaning this delayed rebound could play a role in the drug’s therapeutic potential.
“The effects open up the possibility of understanding the long-term effects of psychedelics through the lenses of sleep research,” the researchers explained. “The literature on slow waves suggest that they might have an effect on plasticity, and that a state with global slow waves – as we report, might be the media to support global brain changes, although that is still speculation from our end.”
“We can push that idea further, with slow waves being generally associated with a sense of disconnection from the environment, one might think that they could be the basis of the psychedelic experience. Our results were already successfully replicated in humans as shown by the work of George Blackburne from UCL.”
While these findings offer new insights, the scientists note that the slow waves caused by the drug cannot be labeled as true sleep waves. The electrical signals were smaller in amplitude than natural sleep waves, and fast brain waves typical of normal wakefulness were still present in the background.
There is a risk of misinterpreting this state as an exact substitute for natural rest. The researchers suggest that the drug instead creates a unique hybrid state that temporarily disconnects the brain from the external environment.
“In the early stages of sleep research, sleep was subdivided into stages that are still relevant today,” the researchers said. “One stage in particular was quite puzzling. The French neuroscientist Michel Jouvet called this state ‘Paradoxical Sleep’ (referred to as REM sleep in non-French labs) to describe the strange coexistence of an awake brain state within the deepest stage of sleep. Mirroring this, we observed an ‘asleep’ brain in animals that were unequivocally awake. Rather than calling our finding the psychedelic state, we wanted to call it ‘Paradoxical Wake’ in homage to the pioneering work of 1950s sleep research.”
Future studies will need to explore whether this unique brain state directly causes the long-lasting 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 recovering from mental illness.
The study, “Vigilance state dissociation induced by 5-MeO-DMT in mice,” was authored by Benjamin J. B. Bréant, José Prius Mengual, Alexander Andrews, Anna Hoerder-Suabedissen, Jasmin Patel, David M. Bannerman, Trevor Sharp & Vladyslav V. Vyazovskiy.
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