Three Psychedelics, One Shared Brain Signature: What a New Stanford Study Means for Practitioners

A study in the Proceedings of the National Academy of Sciences, reported this week, offers one of the clearer pictures so far of what MDMA, psilocybin and LSD have in common in the brain. A team led by Adam R. Pines and Leanne M. Williams at Stanford University found that all three substances dampened activity travelling through the default mode network, and that the pattern showed up in mice as well as in people.

This is not a treatment study, and it does not tell us who will benefit from psychedelic-assisted therapy. What it offers practitioners is a more concrete way of understanding why screening matters, and why some people experience a frightening loss of control during a session.

Medically reviewed by Jacque Lovely, RN, MN, MBA, PMP, Reg #74334.

What the researchers did

The brain moves information in two directions. Bottom-up signals travel from sensory areas upward into higher-order regions. Top-down signals travel the other way, from cognitive regions down to sensory areas. The default mode network is a collection of brain regions associated with introspection and daydreaming.

Rather than treating brain regions as fixed points, the Stanford team adapted optical flow, a technique borrowed from video analysis, to follow the wave-like movement of signals across the surface of the brain and to measure which direction those waves were heading.

They applied the method to four existing datasets. In the first, 14 volunteers had functional MRI scans after MDMA, a placebo, or no drug. In the second, six volunteers were scanned after psilocybin and compared against both their own baseline scans and methylphenidate, a stimulant used as an active placebo. In the third, 18 volunteers received LSD by infusion or a saline placebo. The fourth involved 14 mice, imaged with widefield calcium imaging after LSD, diazepam or dexmedetomidine.

What they found

Across the three human datasets, each substance reduced the overall magnitude of activity moving through the default mode network.

MDMA and LSD also reduced the share of that activity travelling bottom-up. Psilocybin moved in the same direction, but the result was not statistically significant. According to the published report, the authors suggest that lingering drug effects may have altered the baseline scans.

The mouse data pointed the same way. LSD reduced both the magnitude and the bottom-up share of activity. Diazepam reduced bottom-up signals to a lesser extent, and dexmedetomidine did the opposite, increasing them. Seeing the LSD pattern in a second species, with a different imaging method, makes it less likely that the human finding is an artifact of how fMRI works.

One finding will stand out to anyone who has supported a client through a difficult session. In the MDMA dataset, the participants with the largest drop in bottom-up signalling were also the ones who reported the most intense feelings of impaired control and the greatest dread of ego dissolution.

Why this matters clinically

The report draws two implications, and both are hypotheses rather than tested conclusions.

The first concerns depression. Ruminative depression is characterized by excessive automatic thoughts and abnormal bottom-up signalling. If psychedelics quiet that flow, it might help explain why some trial participants with depression report relief. This study did not include anyone with depression, so it cannot confirm that.

The second concerns risk. People at risk for psychosis already have impaired bottom-up processing. Reducing it further could make their symptoms worse. That offers a biological rationale for something clinical protocols already do, which is to screen carefully for personal and family history of psychotic illness.

What this means for practitioners

Screening has a mechanism behind it. Exclusion criteria can feel like blanket caution. Research like this suggests they may reflect how these substances act on brain systems that are already vulnerable in some people.

Loss of control may be part of the pharmacology, not a sign that something has gone wrong. If the degree of bottom-up reduction tracks with feelings of impaired control, then preparation sessions that name this possibility in advance, and a steady, supportive presence during dosing, are responding to something real. The study did not test any preparation approach, so this is an inference, but it is consistent with how careful protocols are already designed.

Mechanism studies need to be read critically. A practitioner who can explain what a study like this does and does not show is better placed to have honest informed-consent conversations with patients who arrive having read the headlines.

The limits of the evidence

The samples in all four datasets are small, which limits what can be said about individual differences. The analysis looked only at the outer surface of the brain, so deeper structures were not measured. Human imaging has limits in both spatial and temporal resolution. And every participant was either a healthy volunteer or a laboratory mouse. Larger datasets and studies in clinical populations will be needed before these patterns can be linked to therapeutic outcomes.

The Canadian context

Health Canada states that there are currently no approved therapeutic products containing psilocybin in Canada or elsewhere, and describes clinical trials as the most appropriate and effective way to advance research with unapproved drugs. Since January 2022, healthcare practitioners have also been able to request access through Health Canada's case-by-case authorization pathway for patients with serious or life-threatening conditions when conventional therapies have failed, are unsuitable or are unavailable.

In both pathways, screening, preparation and in-session support rest with the care team, and understanding the emerging science is part of doing that work well.

If you are a healthcare professional considering this field, ATMA CENA's psychedelic therapy training programs are a place to start. Most courses are delivered online, and the Advanced Pathways are complete programs that include the Psychedelic Therapy Foundations course as part one. To talk through which option fits your scope of practice, you can book a call with a program advisor.

Sources

1. Psychedelics disrupt hierarchical cortical propagations in the default mode network of humans and mice. Proceedings of the National Academy of Sciences, 2026.
2. Psychedelics reduce bottom-up brain activity in the default mode network. PsyPost, 2026.
3. Psilocybin and psilocin (Magic mushrooms). Health Canada, 2025.