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.