What The Hype Got Wrong

I used to be that person who forwarded every psilocybin study to anyone who would read it. The early research felt like it was confirming something most of us already suspected, that the medical establishment had spent decades ignoring one of the most promising tools in mental health, and that the tide was finally turning. I wasn't wrong that something was there. I was wrong about how certain we were.

This week, that certainty took a real hit.

Two studies dropped in JAMA Psychiatry on March 18th, and the conversation they've started is the most important one in psychedelics research right now. Not because psilocybin is dead. But because the way we've been measuring it might have been broken from the start.

The central issue is blinding. In a proper clinical trial, participants aren't supposed to know whether they're taking the real drug or a placebo. With psychedelics, that's nearly impossible, the hallucinations give it away almost every time. Studies have found that up to 90–95% of participants can correctly guess their treatment allocation. So when someone in a psilocybin study improves, you can't cleanly separate the drug's effect from the effect of knowing you got the drug.

This is what researchers call the expectancy problem. And it cuts both ways. The people who know they got psilocybin are hopeful, expectant, primed for transformation. The people who know they got the placebo are disappointed, and that disappointment has its own measurable effect. Balázs Szigeti at UCSF has named it the "knowcebo effect": a kind of negative psychedelic experience that comes from realizing you got the dummy pill.

When your control group is deflated and your treatment group is inflated, the gap between them looks bigger than it is.

That's the story most early psilocybin trials may have been telling.

The first study called the EPISODE trial; a rigorously designed German RCT gave 144 people with treatment-resistant depression either high-dose psilocybin or an active placebo. The volunteers who got psilocybin did show improvement, but it was not significantly better than the improvement seen in the placebo group. And while psilocybin produced a bigger symptom reduction at six weeks, the divergence in results led the authors to call the findings "inconclusive."

The second study took a different approach. Instead of comparing psilocybin to a placebo, it compared psilocybin to open-label antidepressant trials, studies where people also knew they were getting the real drug. Pooling data from 24 trials across both categories, the team found no statistically significant difference in patient improvement between psychedelic therapy and open-label antidepressants.

In other words, when you remove the expectancy advantage from psilocybin and the knowcebo disadvantage from the comparison group it looks roughly as effective as the antidepressants people have been dismissing for years.

That's not nothing. But it's also not the revolution.

Here's the thing "inconclusive" is not the same as "doesn't work."

Several researchers commenting on the findings noted that the EPISODE trial still showed statistically significant and clinically meaningful benefit on some measures and that those benefits appeared larger after a second dose six weeks after the first. There are real patients with treatment-resistant depression who improved.

That matters.

What these studies are doing is recalibrating. As one researcher put it, the most important question isn't about the mechanism, it's about durability. If the benefits last over time, the question of placebo response becomes less relevant. A drug that produces a lasting structural change in how someone relates to their own suffering is a different thing than one that just makes you feel better for a while because you expected to.

The structural remodeling hypothesis is the idea that psilocybin's lasting effects come from actual changes in neural architecture, not just mood which is still very much alive.

What's being questioned is whether the early clinical data was clean enough to support the hype that followed it.

Meanwhile, in Humboldt County, a local resident was poisoned by a western destroying angel mushroom they had mistaken for a puffball and the detail that keeps standing out is that experienced local foragers made the same misidentification. Since November 2025, California has recorded 41 poisoning cases, four deaths, and multiple people requiring liver transplants.

The contrast here is hard to ignore. On one end, psilocybin research is being forced into a more honest accounting of what it actually knows. On the other, people are being harmed by the gap between cultural enthusiasm for mushrooms and the baseline knowledge required to interact with them safely.

Both problems share the same root, excitement that outpaced rigor.

The fungi story that got less attention than it deserved this week came out of Johns Hopkins. Researchers showed that oyster and turkey tail mushrooms, two common white-rot species can break down a wide range of psychoactive pharmaceuticals found in biosolids, the material left over from wastewater treatment that gets spread on farmland as fertilizer.

The implication is significant: drug residues, antidepressants, opioids, other compounds currently make it into soil and water systems through biosolids applications. Fungi that can degrade those compounds before they hit the land could meaningfully reduce environmental and public health contamination.

It's a reminder that the most important fungi research often has nothing to do with consciousness. The organisms doing the quiet, unsexy work of breaking down pharmaceutical waste in the ground probably won't show up on wellness Instagram. But they might matter more in the long run than anything happening in a clinical trial.

On March 19th, King County, Washington, moved an ordinance toward its March 24th council meeting that would decriminalize psilocybin mushrooms. Veterans and disability advocates spoke in support. One co-founder of a local psychedelic society described recovering mobility after traditional medicine failed her.

The legal landscape is still moving slowly, unevenly, responding more to lived experience than to clinical consensus. Which is probably fine. The people showing up to city council meetings to advocate for psilocybin aren't doing it because of a meta-analysis. They're doing it because something changed for them personally. That's not nothing either. It just doesn't tell us what we need to know at the population level.

The research still has to do that work. And right now, the research is telling us it needs to start over with better tools.

That's not a loss. That's science doing what it's supposed to do, just a little later than anyone wanted.

There's a pattern running through everything this week, and it's worth naming before you close this tab.

White-rot fungi quietly degrading pharmaceutical waste in biosolids. A forager in Humboldt County killed by a mushroom that fooled people who should have known better. Two clinical trials forcing a reckoning with a decade of credulous coverage. A county council weighing decriminalization while the science is still sorting itself out.

None of these stories are really about mushrooms. They're about what happens when enthusiasm gets ahead of understanding and what it costs when it does. Sometimes the cost is a wasted decade of inflated research. Sometimes it's a liver transplant. Sometimes it's a policy that arrives after the people who needed it most already gave up waiting.

The through line isn't doom. The fungi are still doing real work. The psilocybin research is still worth pursuing, it's just being asked, finally, to prove itself under harder conditions.

The legal landscape is still moving.

But the honest version of this moment is that we are earlier in all of this than the coverage suggested. That's fine.

Early is where the actual work happens.

Another week in the books!

Hope you enjoyed this weeks version of The Spore Drop.

See ya next week! 🍄