@realjoshsiegel.bsky.social
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A final note - the collective progress of our neuroscience community will change human knowledge and mental health in ways you cant imagine. The thrill of publishing this work is tempered by the devastating loss of a brilliant member of our community - nolanrwilliams.com
Bauer and I dreamt this up 5 years ago – I was working on psilocybin fMRI. I was worried because serotonin is vasoactive (hint: it’s IN THEN NAME). Was this impacting psychedelic fMRI? Adam, Jonah, Jordan and team just happened to have the perfect set up to find out the answer.
Why is this a big deal?

fMRI / BOLD-based measures (which rely on blood dynamics) may mis-estimate or mis-interpret psychedelic effects. Some effects attributed to “functional connectivity” might in part be vascular change.
The hemodynamic response to neural activity gets tighter. Which is weird! And honestly not exactly what I expected.
My favorite part is that we saw very similar changes in my human psilocybin fMRI data!
Padawer-Curry and team recorded neuronal and hemodynamic (blood-based) signals simultaneously before and after giving a psychedelic to mice. Surprise: they diverge.

In simple terms: the normal link between neurons firing and local blood flow is distorted.
Reposted
Ever wondered if your interesting brain-behavior correlation was over- or under-estimated due to head motion, but were afraid to ask? We’ve created a motion impact score for detecting spurious brain-behavior associations, now available in Nature Communications!
doi.org/10.1038/s414...
What went wrong with MDMA for PTSD at the FDA?
Was the recent Compass trial a success or a letdown?
Should practitioners have to "trip" themselves?

I sat down with the great and wise Dr. Mark Gold to explore the controversy and bleeding edges of psychedelic science:

youtube.com/watch?v=oitU...
"Neuroscience, Clinical Trials, and the Future of Psychedelic Medicine” with Joshua Siegel, MD, PhD
YouTube video by Hatherleigh Behavioral Health
youtube.com
Reposted
I still get chills

Meet Mike
*30+ years severe depression
*first hospitalized @ 13y
*20 meds
*3 rounds of ECT
*2 near-fatal suicide attempts

Mike felt joy for the first time in decades after we turned on his new brain pacemaker or PACE

see videos, read paper, follow thread
doi.org/10.31234/osf...
Reposted
We have argued that the brain’s Action Mode Network controls functions required for goal-directed behavior. www.nature.com/articles/s41...

Now, in new work, we show that AMN contains distinct subnetworks for making decisions, implementing actions, and processing feedback. doi.org/10.1073/pnas...
Anyone going to Psychedelic Science 2025 in Denver?

I'm on a panel - "Beyond the Blobs: Visualizing the Psychedelic Brain" - with a film maker (Ethan Goldwater) and he made an incredible video JUST for the panel.

drive.google.com/file/d/1317D...
BeyondtheBlobs_v005_9x16.mp4
drive.google.com
This extraordinary psychedelic dataset is now fully/freely available to all!

All the info to access & use it in a newly published Nature Scientific Data Resource: rdcu.be/epxe7

Thanks to the incredible team who created it - Subha S, Rick R, Ginger N, to name a few.

Translate that into Japanese!
"Effects of Psilocybin on Clergy..."

The resutls are just ... incredible.

"participants rated their psilocybin experiences to be among the top five most spiritually significant (96%) of their lives..."

liebertpub.com/doi/10.1089/...
Effects of Psilocybin on Religious and Spiritual Attitudes and Behaviors in Clergy from Various Major World Religions | Psychedelic Medicine
Background: Although historical writings, anthropological accounts, and experimental studies document associations between psilocybin use and religion, no prospective experimental study has investigated how the effects of psilocybin are experienced and interpreted by religious clergy. This exploratory study evaluated the overall safety and the acute and enduring effects of psilocybin in clergy. Methods: Participants were psychedelic-naïve clergy from various major world religions. A randomized, parallel group, waitlist control design was used to assess the effects of two supported psilocybin sessions, with participants receiving 20 and then 20 or 30 mg/70 kg about 1 month later. Outcomes were compared between the Immediate Group (n = 13) and the Delayed Group (n = 16) at 6 months after screening using self-report measures. The effects of psilocybin were also assessed on session days and 4 and 16 months after the second psilocybin session in the 24 participants who completed both sessions. Results: The primary outcome assessment at 6 months after screening showed that, compared with the delayed control group, participants who had received psilocybin reported significantly greater positive changes in their religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in their non-religious attitudes, moods, and behavior. Follow-up assessments showed that positive changes in religious and non-religious attitudes and behavior were sustained through 16 months after the second psilocybin session. At that time, participants rated at least one of their psilocybin experiences to be among the top five most spiritually significant (96%), profoundly sacred (92%), psychologically insightful (83%), and psychologically meaningful (79%) of their lives. Furthermore, 42% rated one of their experiences to be the single most profound of their lifetime. At 16-months follow-up, most (79%) strongly endorsed that the experiences had positive effects on their religious practices (e.g., prayer or meditation) and their daily sense of the sacred, and most (71%) reported positive changes in their appreciation of religious traditions other than their own. Although no serious adverse events were reported, 46% rated a psilocybin experience as among the top five most psychologically challenging of their lives. Conclusions: In this population of clergy, psilocybin administration was safe and increased multiple domains of overall psychological well-being including positive changes in religious attitudes and behavior as well as their vocation as a religious leader. The study was limited by a waitlist control design, homogenous sample, and the use of some unvalidated outcome measures. Further research with more rigorous control conditions and diverse samples is needed.
liebertpub.com
The brain signature of a single dose of Ritalin in six participants in our precision functional mapping study was highly significant and well matched to stimulant effects determined in thousands of subjects in the ABCD data set.

PFM provides powerful drug bio markers!

Stay tuned for more on this
We were so surprised, we replicated our findings in a precision imaging drug trial of healthy adults taking an experimentally controlled dose of Ritalin (methylphenidate). The stimulant trial brain maps were highly correlated with those from ABCD p < 0.001.
Reposted
My med school textbook says stimulants like Ritalin treat hyperactivity by “stimulating” the brain’s attention and cognitive control systems. We studied children taking stimulants in the ABCD Study, and the largest differences were actually in arousal and reward networks! Check out our preprint!
I agree! We are held accountable by the IRB. But who holds the IRB accountable!?
Major praise to the @nyulangone.bsky.social podcast team.

I expected just a little internal thing, but they did an AMAZING job digging into the science and creating a great show.

Check it out -
YouTube (full-length): youtu.be/h8Thc-BDvZ0A...
Spotify: open.spotify.com/episode/3WHK...
youtu.be
It's terrifying to watch a tyrannical power grab in America.

But also ... kind of fascinating... in a twisted way.

Really brings the history books to life, huh?

www.economist.com/leaders/2025...
Donald Trump: the would-be king
America is fated to wage a titanic struggle over the power of the president
www.economist.com
Reposted
The advancements in brainstem imaging will make it possible to examine a host of clinically relevent structures like the eriaqueductal gray and substantia nigra in humans, something that has been very hard to do well previously
This is *crucial* to the future translational potential of resting fMRI
Reposted
It's shocking how little is known about the brainstem red nucleus. In our new paper “The human brainstem’s red nucleus was upgraded to support goal-directed action” out now in @naturecomms.bsky.social we show that current thinking on the red nucleus is in need of a serious upgrade. rdcu.be/ehbOy
Reposted
Our latest study identifies a specific cell type and receptor essential for psilocybin’s long-lasting neural and behavioral effects 🍄🔬🧠🧪

Led by Ling-Xiao Shao and @ItsClaraLiao

Funded by @NIH @NIMHgov

📄 Read in @nature.com - www.nature.com/articles/s41...

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Psilocybin’s lasting action requires pyramidal cell types and 5-HT2A receptors - Nature
A pyramidal cell type and the 5-HT2A receptor in the medial frontal cortex have essential roles in psilocybin’s long-term drug action.
www.nature.com
Just heard a fascinating talk by Mir Jalil Razavi! 🤯

Cortical folding is driven by surface expansion. Tiny differences in cortical thickness and starting morphology drive patterning of the brain surface.

Crucial info to anyone who wants to localize brain function!

nature.com/articles/sre...
Cortical Folding Pattern and its Consistency Induced by Biological Growth - Scientific Reports
Scientific Reports - Cortical Folding Pattern and its Consistency Induced by Biological Growth
nature.com