Research & context · October 31, 2026
We’ve gotten used to talking about LSD and psilocybin as if they’re variations on the same theme. Both are classic psychedelics. Both act on serotonin receptors. Both can produce startling changes in perception, emotion, and a person’s sense of self.
But underneath those similarities, the brain may be doing quite different things.
In a new Nature Neuroscience paper, researchers in Copenhagen combined two kinds of brain scans to watch what happened as volunteers experienced LSD. They then compared their results with earlier measurements from a separate group given psilocybin. One finding was especially strange: blood flow through the brain increased after LSD, while the psilocybin group showed a decrease. A measure of how strongly signals across the brain were correlated also moved in opposing directions.
That’s an intriguing contrast. It isn’t proof that one drug is safer, better for depression, or even more powerful. And it comes with a sample-size warning big enough to put on the front page.
Seven people, two kinds of scan
The experiment wasn’t a treatment trial. The volunteers were healthy, and the researchers weren’t measuring whether anyone recovered from depression or anxiety. They wanted to see how a psychedelic interacts with the living human brain, from the receptor molecules it binds to, all the way out to blood flow and the changing patterns of activity picked up by a scanner.
Eleven people took part in the LSD arm and completed baseline imaging. Seven produced usable combined scans during the drug’s peak effects. The investigators used PET imaging to estimate how much LSD occupied a particular serotonin receptor, 5-HT2A, and MRI techniques to measure blood flow and changes in functional connectivity.
These are different measurements. A PET scan can help show where a drug is engaging its molecular target. An MRI blood-flow measurement tells researchers about circulation through brain tissue. Functional MRI looks at the relationship between signals in different regions. None of them provides a direct camera feed of what somebody thinks or feels.
The 5-HT2A receptor is central to the effects of classic psychedelics, but drugs that engage the same receptor need not set off identical cascades in the brain. That is part of what makes this study worth reading.
The numbers are striking. So is the small print.
In the seven participants with usable peak scans, LSD was associated with about a 19% increase in global cerebral blood flow and a 28% increase in flow through the internal carotid arteries. The team did not observe a corresponding increase in the diameter of those arteries.
Meanwhile, a whole-brain measure of signal correlation, known as GCOR, decreased across much of the cortex. Areas involved in vision and parts of the default-mode network were among those showing changes.
The comparison with psilocybin came from a different group: 25 people who had participated in an earlier study. In that cohort, the direction of the average findings was reversed. Psilocybin was associated with lower cerebral blood flow and higher global correlation.
It would be tempting to turn this into a tidy diagram: LSD makes the brain flow faster and talk less; mushrooms make it flow slower and talk more. Biology doesn’t really cooperate with that kind of slogan. Blood flow is not a meter for intelligence, consciousness, or the richness of an experience. And a statistical measure of global correlation is not a simple measure of how well your neurons are communicating.
There is another complication. This was not a randomized head-to-head experiment assigning participants to LSD or psilocybin under identical conditions. The teams compared two datasets, with their own participants and measurement contexts. Differences between the groups, timing, and methods could matter.
What the researchers could see for the first time
For decades, scientists have known that LSD acts strongly at serotonin receptors. But measuring a drug’s occupation of those receptors in a living human brain, while also measuring changes in circulation and network activity, has been a harder problem.
By combining PET and MRI during the same experimental sessions, the researchers built an unusually detailed picture of what happens at several levels. They reported high-affinity binding to 5-HT2A receptors and a dose–occupancy relationship that gives researchers something more concrete than guessing from the amount swallowed.
They also noticed that blood concentrations of LSD and the intensity of the experience didn’t rise and fall in lockstep. The strongest subjective effects could lag behind the peak concentration measured in blood. Pharmacologists call that sort of delayed relationship hysteresis. For the rest of us, it means the amount of drug circulating at one moment doesn’t perfectly tell you how intense the experience feels at that moment.
This matters for psychedelic research because it’s another warning against assuming that dose, blood concentration, receptor engagement, brain imaging, and subjective experience are all interchangeable. They’re related, but they’re not the same thing.
Could the blood vessels be distorting our picture of psychedelic brains?
Here’s the question I keep coming back to. Functional MRI doesn’t record electrical activity from neurons directly. It tracks blood-oxygen-related signals that researchers use as an indirect window into brain activity.
But psychedelics can affect blood vessels as well as neurons. If a drug changes the circulation itself, how confidently can scientists interpret an altered MRI signal as a change in neural communication?
The new study doesn’t fully answer that question. It does make it harder to ignore. Across the LSD and psilocybin data, changes in blood flow and the global connectivity measure tended to relate negatively to one another, even though each drug moved those measures in different directions overall. That could point to important differences in neurovascular coupling—the relationship between neural activity and the blood flow that supports it.
In other words, when a psychedelic brain scan lights up or quiets down, part of the story may be happening in the blood vessels. That doesn’t make earlier brain-scan research worthless. It means we should be precise about what the instrument is actually measuring.
Does this mean LSD and psilocybin work differently as medicines?
Possibly. But this particular research can’t tell us how their benefits compare.
No one in the experiment was being treated for depression. There was no clinical outcome to compare with blood flow. A physiological difference between two drugs doesn’t necessarily turn into a meaningful difference in their usefulness for patients. It might. Or it might be incidental, context-dependent, or less important than some other mechanism we haven’t isolated yet.
That distinction is easy to lose in a field where every new scan is sometimes framed as evidence of a breakthrough. The imaging results are the finding. Claims about lasting therapeutic benefit would be a separate question requiring a separate kind of study.
It’s also worth remembering how tiny the LSD imaging sample was. Seven people can reveal a signal worth chasing, particularly with sophisticated techniques, but they can’t establish how widely that signal applies across ages, health conditions, medications, or doses. Two LSD participants were unable to complete scanning because of adverse effects, and another two because of scanner failures, leaving that usable sample of seven. Those missing observations matter when interpreting the results.
The more interesting story isn’t a contest
For readers used to comparing the substances through trip reports, this research offers a refreshing change of scale. Instead of asking which trip is more visual or spiritually profound, it asks what is happening when the same broad family of drugs meets a very complicated organ.
The answer, so far, is that sharing a famous receptor doesn’t guarantee sharing the same full-body physiology. That’s scientifically interesting without making one drug a winner and the other a loser.
We previously looked at how psilocybin’s effects on brain activity can depend on context. The Copenhagen findings add another layer: even two closely related psychedelic substances may alter the measurements behind our favorite brain-scan narratives in different ways.
The researchers now have a better foundation for asking how receptor engagement, circulation, and neural activity interact. What they don’t have—and don’t pretend to have—is a clinical verdict.
For now, the useful takeaway is modest but fascinating: LSD and psilocybin may look like cousins from the outside, but the brain’s response is much more complicated than a shared psychedelic label suggests.
Sources and further reading
- McCulloch D.E.W. et al., “Investigating molecular and hemodynamic effects of LSD in the human brain,” Nature Neuroscience, published October 12, 2026. DOI: 10.1038/s41593-026-02462-2.
- PubMed record and research abstract.
- Medical Xpress, October 28, 2026: interview and reporting on the study.
Editorial note: This article is about basic neuroscience research, not medical advice or a recommendation to use psychedelic drugs. The two compounds were not tested against one another as treatments in this study.