In a recent study published in Scientific Reports, researchers have uncovered connections between the psychoactive effects of classical psychedelics and brain activity patterns that resemble those seen during sleep. The findings suggest that psychedelic substances induce a unique state that integrates waking behaviors with sleep-like brain waves.
Classical psychedelics, including compounds like 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are known to induce profound changes in perception, emotion, cognition, and movement. These substances, structurally similar to serotonin, have been the subject of interest due to their potential therapeutic effects and their ability to produce states similar to dreaming. However, the exact brain mechanisms underlying these effects remain largely unknown.
“As a sleep and memory researcher, I’ve been interested in psychedelic states as waking proxies of dreaming,” said study author Sidarta Ribeiro, a full professor of neuroscience at the Brain Institute of the Federal University of Rio Grande do Norte, an associate researcher of the Center for Strategic Studies of Fundação Oswaldo Cruz (FIOCRUZ), and author of The Oracle of Night.
“We have previously found that psychedelics can induce neuroplasticity akin to that induced by sleep. This prompted our interest in assessing neural markers of slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep after the administration of 5-MeO-DMT, a potent classical psychedelic substance.”
Slow-wave sleep (SWS) is a deep stage of sleep characterized by slow, high-amplitude brain waves called delta waves. It is crucial for physical restoration, memory consolidation, and overall brain health. Rapid-eye-movement (REM) sleep, on the other hand, is marked by low-amplitude, mixed-frequency brain activity, similar to an awake state, and is named for the quick, random movements of the eyes. REM sleep is essential for processing emotions, learning, and memory, and is when most dreaming occurs.
The researchers conducted their study using 17 adult male rats. These animals were housed under controlled conditions and subjected to a series of experimental sessions. The focus was on the acute effects of 5-MeO-DMT, a psychedelic compound, on brain activity.
To investigate this, the team used electrodes to record brain activity from two key areas: the medial prefrontal cortex (mPFC) and the hippocampus (HP). These regions are crucial for cognition and navigation, respectively. The electrodes were carefully implanted in the rats’ brains, allowing for detailed monitoring of electrical activity.
The experimental design involved administering different doses of 5-MeO-DMT or saline (as a control) to the rats and then recording their brain activity and behaviors. The recordings were made while the rats moved freely in an arena, which provided a naturalistic setting for observing the effects of the drug.
Rats exhibited a range of altered behaviors after receiving 5-MeO-DMT. These included uncoordinated movements, periods of stillness, and stereotyped behaviors like head twitching.
The researchers found that 5-MeO-DMT induced noticeable changes in brain wave patterns, particularly in the hippocampus. Theta waves, which dominate during active behavior and REM sleep, showed a significant decrease in power after drug administration. This was not solely due to changes in the rats’ movement speeds, suggesting a direct effect of the drug on brain activity.
The researchers also found changes in gamma waves, which are associated with higher brain functions like attention and memory. Both slow and mid-gamma oscillations were affected, with a dose-dependent reduction in their power and modulation by theta waves. This indicates that 5-MeO-DMT alters the complex interplay between different brain rhythms.
Using a technique called state mapping, which plots brain activity patterns, the researchers observed that 5-MeO-DMT induced transitions between waking-like and sleep-like states. Even though the rats were awake and moving, their brain activity resembled that of sleep states, particularly slow-wave sleep (SWS) and REM sleep. This suggests that the drug creates a hybrid state combining elements of both wakefulness and sleep.
“We were quite surprised by the fact that the transition probabilities across states as defined by the brainwaves, i.e., the chance of going from one state to the other were not significantly changed after 5-MeO-DMT administration, despite the fact that the animals were very obviously awake, moving around and performing stereotyped behaviors,” Ribeiro told PsyPost.
“The take home message of our study is that rats will be overtly awake after the administration of 5-MeO-DMT, and yet their brainwaves will show the continuation of the sleep-wake cycle. We suspect that this could be the basis for the existence of psychedelic sub-states in which rats (and presumably humans) are more extroverted (waking-like) or introverted (sleep-like). Furthermore, these introverted states may come in two flavors, one more slumberish (SWS-like) and another more oneiric (REM-like).”
The findings provide new insights into the complex effects of psychedelics on the brain. Rats have a brain structure that, while simpler, shares many functional similarities with the human brain. These similarities allow researchers to draw parallels between rat and human brain function and make inferences about how psychedelics might affect human brains.
However, findings in rats may not fully translate to humans due to species-specific differences in metabolism, receptor distribution, and overall physiology. “Rats are not humans, so we cannot assess their subjective experience directly,” Ribeiro noted. He plans to “follow-up these results in human subjects, and then explore in detail the features of each of these three psychedelic substates (waking-like, SWS-like and REM-like).”
“It is time for psychedelics to be fully legalized and freely investigated,” Ribeiro added.
The study, “5‑MeO‑DMT induces sleep‑like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats,” was authored by Annie C. Souza, Bryan C. Souza, Arthur França, Marzieh Moradi, Nicholy C. Souza, Katarina E. Leão, Adriano B. L. Tort, Richardson N. Leão, Vítor Lopes-dos-Santos, and Sidarta Ribeiro.