First synthesized in a laboratory in 1938 by the Swiss chemist Albert Hofmann, lysergic acid diethylamide, better known by its acronym LSD, is one of the most potent and most extensively studied psychedelics.
Taken in very small doses, it profoundly alters perception, causing visual hallucinations, a distorted sense of time and a feeling of merging with one’s surroundings.
After being the subject of extensive psychiatric studies in the 1950s and 1960s, and then long associated with recreational or spiritual use, LSD has attracted renewed scientific interest over the past decade, driven by research into the therapeutic potential of psychedelics for treating depression, anxiety and post-traumatic stress disorder.
Yet despite this enthusiasm, how this molecule transforms the brain’s electrical activity remains poorly understood. And does it do so in the same way as other psychedelics? Answering these questions is essential to developing these treatments responsibly, but also to uncovering the mechanisms by which the brain gives rise to consciousness.
A new international study published in the journal Communications Biology provides some answers: LSD does not merely weaken the brain’s rhythms, it speeds them up, and it makes brain activity more fractal, with signals recurring in patterns across different time scales. This acceleration may even be a signature unique to LSD.
The study was co-authored by Université de Montréal by doctoral student Venkatesh Subramani, supervised by Karim Jerbi, a professor in the Department of Psychology and a researcher at Mila – the Quebec Artificial Intelligence Institute, and by Nicolas Farrugia and Giulia Lioi of IMT Atlantique in Brest, France. Suresh Muthukumaraswamy of the University of Auckland in New Zealand and Robin Carhart-Harris of the University of California, San Francisco, also collaborated in the study.
Rethinking “desynchronization”
The collective activity of neurons produces electrical rhythms known as “brain waves.” Alpha waves dominate when we are at rest with our eyes closed; beta waves are associated with concentration and decision-making, among other things.
Under psychedelics, these waves appear less intense, which is generally interpreted as “desynchronization,” meaning that neurons fire less in unison.
But conventional methods did not always distinguish between a genuine weakening of the waves and a change in their frequency, that is, the number of oscillations per second.
Speeding up brain rhythms
To find out whether these rhythms were truly weakening, changing speed, or both, the research team used state-of-the-art signal-processing methods combined with artificial intelligence to analyze magnetoencephalography (MEG) data collected at Imperial College London by Robin Carhart-Harris’s team.
MEG measures, to the millisecond, the tiny magnetic fields produced by neuronal activity. For the study, 17 healthy volunteers took part in two sessions, two weeks apart: in one, they received an intravenous injection of LSD (75 micrograms, roughly the weight of a grain of salt); in the other, a placebo (a saline solution).
The team discovered that under LSD, alpha and beta waves do not simply weaken: they also increase in frequency, that is, the speed at which they oscillate. Wave oscillations are measured in hertz, the number of cycles per second. Under LSD, alpha waves increase by about 2 hertz and beta waves by about 5 hertz, across large areas of the cortex.
“Imagine a radio station switching its broadcast frequency from 99.5 to 100.5 FM,” said Jerbi. “If your radio stays tuned to 99.5, the signal may seem distorted or lost. In the same way, overlooking the shift to faster brain rhythms can lead us to misinterpret LSD’s effects on the brain.”
Unlike certain anesthetics, which slow the alpha rhythm, LSD speeds it up, a sign of a more excitable cortex.
Like a Romanesco broccoli
Beyond brain waves, the researchers found that LSD makes brain activity more complex, more fractal and less predictable, somewhat as if the brain were exploring a broader repertoire of possible behaviours rather than following a steady rhythm.
A fractal is a shape that reappears in each of its parts, even the smallest: every floret of a Romanesco broccoli, for example, is itself a small Romanesco, made up of even smaller florets. Applied to the brain, this concept describes a signal whose patterns recur across different time scales.
The researchers measured this “fractal dimension,” as well as the diversity of patterns in the signal. Both increase under LSD: the brain signal becomes richer in detail and more irregular, much like the outline of a jagged rocky coastline, where every zoom reveals new coves, compared with that of a perfectly straight beach.
The study found that these changes are particularly pronounced in brain regions involved in sensory perception, language, emotion and mental imagery, while the motor cortex remains relatively unaffected. This could explain why psychedelics alter perception and introspection so profoundly without necessarily disrupting movement.
This finding echoes a well-known experience among people who have taken LSD: seeing, especially with their eyes closed, complex geometric patterns such as spirals, tunnels or shapes that repeat endlessly, like fractals. It is tempting to see a link between a more fractal brain and more fractal perceptions.
“Our findings lend support to this intriguing hypothesis, but they do not yet confirm it,” cautioned Jerbi. “We measure the fractal structure of brain signals over time, not the fractal structure of the images people perceive.”
Using AI to uncover signatures
The researchers then trained an AI algorithm to distinguish LSD sessions from placebo sessions based on brain signals alone. By combining all the measures, it does so correctly 88 per cent of the time, compared with 50 per cent by chance alone, they found.
“Our machine-learning algorithm can distinguish brain states under LSD from those under placebo using brain signals alone,” said Subramani. “By examining the clues it relies on, we can identify LSD’s signatures in brain activity.”
These signatures include the complexity and fractality of the signals, changes in their “background noise,” and the speeding up and weakening of alpha and beta rhythms.
Some implications for therapy
Conducted in healthy volunteers after a single dose, the study did not test for any therapeutic effect, but it sheds light on possible mechanisms. According to an influential theory, psychedelics loosen the brain’s expectations, leaving more room for sensory information. The faster and more complex activity observed under LSD is consistent with this idea.
In depression and anxiety, thoughts often get stuck in the same rigid loops. Picture a ski slope at the end of a busy day: skiers keep sliding into the same deep ruts, which become harder and harder to escape. A brain made temporarily more flexible could act like a fresh layer of snow, smoothing over those ruts and making it easier to carve new paths. This idea has yet to be tested in patients.
Meanwhile, a formulation of LSD is already being evaluated for generalized anxiety disorder and depression in phase 3 clinical trials, the final stage of testing before a treatment can be submitted for regulatory approval.
In further research using similar methods, Subramani and his colleagues are now comparing how LSD, psilocybin (the active ingredient in “magic mushrooms”) and DMT (a naturally occurring psychedelic found in ayahuasca, a traditional South American brew) affect the brain.
The scientists’ goal is to better understand how each substance works, track its effects and, eventually, predict how individual patients will respond to treatment.