The Unfinished Sentence Science as covenant — and what it means to rend it

lisagraumlich.substack.com/p/the-unfini...

I have found them in science — in the particular quality of attention that genuine inquiry requires, the willingness to be changed by what you find.

This is not how we usually talk about science. But it is, I would argue, how science actually works at its highest register."

Thin places, in Celtic spiritual tradition, are where the distance between the human and the holy collapses to almost nothing. I have found them in old-growth forests, at the foot of receding subalpine glaciers, in the faces of students the moment something shifts.

Really resonate with this post about science "I have also stood at the edge of what we know and felt something else entirely. The places where a question opens into a larger question. Where the boundary between what I understand and what I am being asked to become starts to thin...

After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication. "

This is from a paper in second round of review, not published yet tho, "During the preparation of this work the author(s) used Claude and ChatGPT in order to generate ideas, refine text, and proof the manuscript.

Yes, response. Thx for the correction. Lots of studies i think are being powered based on these early studies rather than more realistic numbers that are emerging these days. We have done some of the same in our work and it seems we are learning about it together.

To be clear, this is not a guarantee it's going to get FDA approval by any means, I just hadn't been following this closely and it looks like it's made some progress on the pathway.

Looks like Osmind's ketamine "me too" formulation is getting closer to FDA approval, to add to esketamine. This time via IV, rather than intranasal. ir.nrxpharma.com/news-release...

I agree with the conclusion that current data do not justify a claim that PAT outperforms antidepressants. Economic issues will really be at play here. If they are relatively equivalent, but PAT is more expensive, that'll matter a lot.

Yeah, best data these days are suggesting that, for depression, PAT is relatively equivalent to our best established treatments (antidepressants) and has a more rapid response. We need bigger and better studies to see if it can outperform. Sample sizes will probably need to be massive.

To me, this study should have been designed with continuous outcomes as the primary endpoint, which would have been more typical and also more defensible from a power standpoint. But they didn't do that, so here we are. Another underpowered study relative to analytic goals.

The devil is in the details here. This is certainly not supportive of massive PAT effects, but neither is it a damning study.

To me, this mostly reads as a study that was planned using overly optimistic effect sizes on remission, especially given what was a treatment resistant depression sample. The mots comprehensive analyses are suggesting one session of psilocybin for tx-resistant depression is not enough.

If you haven't read the articles, I'd encourage you to do so directly. The Mertens study was based on a power analysis using remission as a primary outcome, which is 1. rare to do and 2. based on absurdly large power estimates. The continuous outcomes on the very same measure (HAM-D) favored PAT.

Psilocybin or Nicotine Patch for Smoking Cessation This pilot randomized clinical trial compares prolonged smoking abstinence rates in smokers receiving psilocybin with those receiving the nicotine patch with both groups receiving manualized smoking c...

Read more here: jamanetwork.com/journals/jam...

Bottom line: This is a promising signal but we need to be cautious about over interpretation of what are still pilot studies. Good pilot data but not proof psilocybin is superior to existing best treatments.

Big thanks to this team for continuing to provide important data.
#psychedelicscience

The 40.5% prolonged abstinence is somewhat higher than the best available treatments. That's genuinely noteworthy for a single dose of anything.

This pilot study justifies a larger, more rigorous trials — ideally against varenicline or more powerful comparators and equal contact time

This pattern — spectacular results in small open-label pilots that shrink in randomized trials — is extremely common in research in general and in psychedelic research in particular. It's a feature of the field, not a bug in this study.

It's also the case the treatment was less intensive.

Also worth noting: psilocybin's effectiveness dropped from the first study to this one:

The 2014 open-label pilot (15 people, more psilocybin doses):
→ 80% point prevalence abstinence at 6 months
→ 53% prolonged abstinence
This RCT (1 psilocybin dose):
→ 52% point prevalence
→ 40.5% prolonged

The comparator problem:

Nicotine patch is arguably the weakest first-line cessation med. Meta-analyses show ~10% prolonged abstinence at 6 months.

Varenicline is more in the 30% range.

CBT is typically in the 20-30% range.

New in JAMA Network Open: Psilocybin beat the nicotine patch 4-to-1 for smoking cessation (40.5% vs 10% for prolonged abstinence). Important study and impressive headline — but what happens when you look under the hood? A thread to unpack this finding. 🧵#psychedelicscience

Research Associate in clinical psychedelic science - Portland Psychotherapy Join an active clinical research lab at the forefront of psychedelic science. As a Research Associate, you will contribute to multiple clinical trials of Research Associate in clinical psychedelic sci...

PIPS is hiring a Research Associate to work on clinical trials of psychedelic-assisted therapy (MDMA, psilocybin). Starting summer 2026. Great for post-bac folks looking for research experience before grad school.

portlandpsychotherapy.com/behavioral-science-research-coordinator-in-portland-oregon/

Jason Luoma, PhD | ACT & Psychedelic Science Podcast Episode · Mentally Flexible · March 5 · 52m

I was just interviewed on the Mentally Flexible Podcast about ACT and Psychedelics. It was a fun interview and I think covered some interesting ground about shame, transcendent emotions, and psychedelic experience. Hope you enjoy it!

podcasts.apple.com/us/podcast/j...

That's an oversimplification but might capture sole of the core pathways. After all, neuroplasticity is just the underlying substrate for more rapid learning. Anywhere in life where we see more rapid learning, we will see more neuroplasticity by definition.

The longer term potential for positive affect changes may have to do with transcendent emotions and experiences setting off new ways of seeing the world and patterns of living that then get reinforced and sustained over time. That reinforcement process would feature dopamine centrally.

The lack of addiction potential may have to do with lack of reliability of the euphoric effects and often slow onset as well as rapid tolerance in classics.

That's a great question I don't know the answer to. I'm a psychologist so my speculation would come more thru understanding the experience versus the neurochemistry.

There were a lot of weaknesses in this small study, so we shouldn't get too excited from this one trial, but it adds to the body of research on psychedelics' impacts on positive motivational circuits. #psychedelicscience

Read more here: doi.org/10.1016/j.ja...

The theory: anhedonia may stem from impaired neuroplasticity in brain reward circuits. Psilocybin's ability to promote neuroplasticity and rewire dysfunctional circuits could help restore the capacity for pleasure and motivation.