An international analysis combining brain imaging data from multiple independent studies has identified common patterns in how psychedelic drugs alter communication between different brain networks. Researchers have found that substances such as psilocybin and LSD reliably increase functional connectivity between brain regions responsible for sensory input and brain regions involved in abstract, associative thinking. The research results were published in a magazine natural medicine.
In recent years, classic psychedelic drugs such as psilocybin, LSD, and DMT have re-entered the mainstream of psychiatric research as experimental treatments for conditions such as depression and anxiety. All of these substances reliably bind to specific types of serotonin receptors in the brain, causing profound changes in perception and consciousness.
To understand how these altered conditions manifest physically, researchers often use functional magnetic resonance imaging. This non-invasive scanning technique measures spontaneous and regulated blood flow in the brain. When people simply rest in the scanner, their brain activity naturally synchronizes into separate large networks. Some of these networks handle basic sensory and motor tasks, while others manage higher cognitive functions such as memory recall, self-reflection, and goal planning.
Previous brain imaging studies on psychedelics have painted a fragmented picture of these network changes. Most studies rely on small sample sizes because collecting data on individuals under the influence of powerful psychotropic drugs is difficult and expensive. Different research groups also apply different statistical methods to their datasets. This unchecked variation has led to conflicting reports, with some labs finding increases in certain brain connections, and others observing just the opposite effect.
To resolve these discrepancies, a global team of scientists formed a collaborative consortium to pool existing brain imaging data into a single standardized analysis. The project was led by neuroscientists Manesh Gilun of the University of California, San Francisco and Danilo Buzdok of McGill University, in collaboration with dozens of independent researchers across three continents.
The research team collected 11 independent datasets originally collected by different laboratories in five countries. In total, the analysis included scans of 273 healthy adults who were given one of five hallucinogens: psilocybin, LSD, DMT, ayahuasca, or mescaline.
The researchers applied a uniform processing pipeline to all brain scans, rather than examining each dataset individually. This standardization helped eliminate variations caused by different laboratories using disparate software programs to clean and prepare raw image data.
The team then analyzed the structural data using a statistical framework known as Bayesian hierarchical modeling. Traditional frequentist statistics often rely on arbitrary numerical thresholds to declare whether a biological effect is present or completely absent. In contrast, Bayesian approaches calculate the continuous probability that a particular change has occurred. This method directly accounts for variation across different participants, drugs, and original study designs, allowing scientists to pinpoint the most reliable brain changes while maintaining graded uncertainty measures.
The integrated analysis identified a consistent brain signature that operates across a variety of psychedelic substances. Researchers found a significant increase in functional connectivity between the brain’s sensory networks and their association networks.
Sensory networks, also known as unimodal networks, process information that comes directly from the environment, such as visual processing or physical touch. Association networks are often referred to as transmodal networks, systems such as the default mode network or the fronto-parietal network. These systems synthesize raw data to support complex thinking, memory construction, and the brain’s baseline resting state.
Under normal circumstances, these sensory and associative systems operate in a highly separated manner, maintaining a strict processing hierarchy that distinguishes between basic cognition and abstract thought. Under the influence of psychedelics, the lines of communication between them become flat. The scans showed that these different networks synchronized and integrated more freely during the drug experience.
The researchers also mapped deep changes in the brain’s subcortical structures. Specifically, they looked at the dorsal striatum, a region comprised of the caudate nucleus and putamen. This region is primarily involved in behavioral selection and linking sensory input to behavioral output. The analysis showed that in psychedelic states, the striatum likely strongly enhances communication with cortical sensory systems.
The researchers noted that when the different drugs were measured against each other, LSD and psilocybin showed virtually identical brain network changes. This overlap is consistent with their comparable pharmacological properties and the large number of participants included with both substances in the pooled data. Mescaline showed a similar pattern of network fusion as LSD and psilocybin.
The substance DMT caused similar architectural changes, but even stronger network disruptions. Ayahuasca showed an unusual pattern in statistical models, which the authors attribute to its complex pharmacology and the extremely small number of participants scanned using that exact substance.
The data collected also challenged prevailing ideas in the neuroimaging field. Previous single-laboratory studies have frequently reported that psychedelics cause an internal collapse of individual functional networks in the brain, a phenomenon often described as intra-network collapse. When the researchers averaged data from all pooled studies, they found this effect to be incredibly weak. Bayesian analysis revealed little statistical certainty about the reduction in connectivity within a given network, calling into question previous claims of network failure.
To extend biological discoveries, several limitations inherent in combining historical data must be considered. The initial studies were conducted over several years and used different magnetic resonance imaging scanners with widely varying magnetic field strengths, recording intervals, and technical specifications.
Participants in different datasets received different drug doses, encountered different administration methods, and underwent scans at widely different chronological points during their respective drug experiences. Some participants received an intravenous injection, while others swallowed a capsule. Some researchers began brain scans immediately after administration, while others waited up to two hours for subjective effects to peak.
Simple differences in study design can also affect interpretation. The majority of the dataset relied on trials that actively compared the drug experience with a placebo-controlled session. However, one dataset did not include any placebo, and another study used a fixed-order design in which the order of drug and placebo conditions was not randomized. Such differences may introduce small biases related to participants’ expectations and novelty.
Head movements remain a persistent challenge in this field of neuroscience. It has been documented that people experiencing the subjective effects of psychedelics are more likely to move around in the scanner than those who sit still after receiving a placebo. Although the data processing pipeline is designed to minimize the influence of participant movement on the results, residual visual noise in the imaging data is still unavoidable.
To build on this foundational map, the scientists suggest that future studies should abandon retrospective pooling and move toward prospectively harmonized trials. In these future projects, multiple laboratories will agree to use identical protocols for drug administration, participant selection parameters, and brain scanning equipment configuration before data is collected.
The study, “An international large-scale analysis of the effects of psychedelic drugs on brain circuit function,” was authored by Manesh Girn, Manoj K. Doss, Leor Roseman, Katrin H. Preller, Fernanda Palhano-Fontes, Lorenzo Pasquini, Frederick S. Barrett, Pablo Mallaroni, Natasha L. Mason, Christopher Timmermann, and Drummond E. McCulloch, Patrick M. Fischer, Brian S. Winston, Flora Muhaes, Felix Müller, Matthias E. Lichti, Franz.
