By now, you’ve probably seen the headlines. Magic mushrooms—aka psilocybin—are the next big thing in treating depression. The hype is high, and so are the volunteers in the studies. But a new analysis just threw a big ol’ mushroom-shaped wrench into the narrative.

Let’s break it down.

The Setup: Antidepressants vs. the Placebo Effect

When scientists test antidepressants, they always pit them against a control group—usually a placebo. Here’s the twist: people in these control groups often still get better. The mind is a powerful thing. In fact, past studies found that folks in antidepressant placebo groups often saw big improvements—just believing you’re getting help makes a difference.

So, how does psilocybin stack up when you strip away the psychedelic glow?

The Meta-Bombshell

Researchers compared results from clinical trials testing:

  • Psilocybin (the compound in magic mushrooms),
  • Esketamine (a fast-acting antidepressant),
  • SSRIs (your everyday antidepressants like Prozac).

But here’s the kicker: they didn’t just look at how well the drugs worked. They looked at how well the placebo groups did in each type of trial.

Spoiler: the placebo group in psilocybin trials did way worse.

How much worse? Placebo patients in psilocybin studies improved only half as much as those in SSRI or esketamine studies.

That’s not just a small dip—that’s a mushroom-sized red flag.

What’s Going On Here?

The researchers think there are two possible explanations:

  1. Different kind of patients – Maybe psilocybin studies pulled in people who are harder to treat. They could be more desperate or less likely to respond to placebo.
  2. Placebo wasn’t really “placebo” – Here’s the trippy part: when someone takes a real psychedelic, they know it. Lights get weird. Time stretches. The sky tells you secrets. So if you’re in the placebo group and don’t feel that… you kinda figure it out.

This “unblinding” (aka realizing you’re not on the real drug) might kill any placebo effect before it has a chance.

Expectation Is Everything

In SSRI and esketamine trials, it’s harder to tell if you’re on the real drug. That means the mind stays in the game—placebo magic still has a shot.

But psilocybin? The line between trip and placebo is as obvious as a lava lamp at a job interview. So participants who know they’re not tripping might also know they’re not “getting help.”

Result: the control group tanks.

What This Means for the Mushroom Movement

Here’s the sobering takeaway:

If the control group is underperforming, the drug might look more effective than it really is.

In other words, psilocybin might not be a miracle—it might just be benefiting from a weaker placebo comparison.

That doesn’t mean psilocybin doesn’t work. It might still be helpful. But we should pump the brakes on the idea that it’s twice as effective as traditional meds—because the math might be off.

What’s Next?

Researchers say future studies need to get smarter:

  • Use better blinding techniques (e.g., active placebos that mimic side effects),
  • Recruit more diverse patients,
  • Run longer trials,
  • Test people with positive expectations for both placebo and psilocybin.

Because if we don’t understand the context, we can’t trust the results.

Bottom Line

Psilocybin still shows promise—but the science isn’t as rock-solid as the headlines make it seem.

Until we get better-designed trials, the “magic” in magic mushrooms might be part placebo, part hype, and part “oops, we forgot the science part.”

Quick Mushroom Cap errr Re-Cap

Magic mushrooms may not be as wildly effective for depression as early studies claimed—not because the drug is useless, but because the control groups in those trials kinda stink. Expectation matters, and if people know they’re not getting the real thing, they stop hoping it’ll help. Future trials need to level the playing field.

Hieronymus F, López E, Werin Sjögren H, Lundberg J. Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression: A Meta-Analysis. JAMA Netw Open. 2025 Jul 1;8(7):e2524119. doi: 10.1001/jamanetworkopen.2025.24119. PMID: 40736734; PMCID: PMC12311713.