In recent years, psychedelic therapy has gone from fringe curiosity to front-page science. The idea that substances like psilocybin — the psychoactive compound found in so-called “magic mushrooms” — could lift the fog of depression has sparked both fascination and controversy.
Now, a new systematic review and meta-analysis published in The BMJ (Metaxa & Clarke, 2024; DOI: 10.1136/bmj-2023-078084) offers one of the clearest pictures yet of what psilocybin might actually do for people living with depression. The verdict? It works better than placebo — but the story is far from simple.
What the study did
Athina-Marina Metaxa and Mike Clarke sifted through a vast landscape of clinical research, gathering results from nine randomized controlled trials involving adults with clinically significant depression.
Their focus was sharp: studies that compared psilocybin itself — not just psychedelic therapy in general — with a non-psychoactive control such as a placebo or niacin. In other words, they wanted to isolate the chemical’s effect, not the therapeutic environment or the psychological support that often accompanies these treatments.
Seven of those trials, representing about 436 participants, were robust enough to be included in the final meta-analysis. That may sound small (because it is), but it’s the best evidence we have so far.
What they found
Across all the studies, psilocybin produced a moderate reduction in depressive symptoms compared with non-active comparators — a standardized effect size (Hedges’ g) of 0.66, which in statistical terms is meaningful.
Interestingly, the effect seemed stronger among people with secondary depression (for instance, depression linked to another serious illness) and in studies that relied on self-reported mood questionnaires rather than clinician-rated scales.
Older participants and those who had used psychedelics before also tended to show greater improvements. These details suggest that psilocybin’s antidepressant effects may depend on factors beyond chemistry alone — experience, expectation, and context all seem to play a role.
What the results mean
The takeaway is cautiously optimistic. Psilocybin clearly has potential. Many participants experienced significant relief from depressive symptoms, often within days. For some, the effects lasted for weeks or even months.
But the authors are careful not to overstate the case. As Metaxa and Clarke note, all the trials so far have small sample sizes and moderate risk of bias. It’s also difficult — maybe impossible — to blind participants completely in psychedelic studies. After all, you can usually tell if you’ve taken psilocybin. That means “expectancy effects” could be influencing the results.
Moreover, most of these studies were conducted in highly controlled, supportive environments — with music, comfortable surroundings, and trained guides. That’s a far cry from what a patient might experience outside of a research setting.
Why this matters
Depression remains one of the leading causes of disability worldwide, and for millions of people, standard antidepressants simply don’t work well enough. Against that backdrop, the excitement around psychedelics is understandable.
Psilocybin’s mechanism — thought to temporarily “disrupt” rigid brain network patterns — could help people break out of destructive thought loops. Combined with therapy, this may lead to lasting psychological change.
But we’re not there yet. Psilocybin remains experimental, and legal access is limited to clinical trials or regulated research programs. Larger, longer studies comparing psilocybin to established antidepressants are urgently needed to confirm both its efficacy and safety.
A cautious optimism
This new BMJ review doesn’t declare psilocybin a miracle cure — but it does suggest that the enthusiasm isn’t pure hype. The data point toward real antidepressant effects, tempered by the need for more rigorous science.
As the authors conclude, future research should explore how much of psilocybin’s benefit comes from the experience itself — the “trip,” the setting, the support — and how much from its direct pharmacological action.
Until we know, psilocybin sits at a fascinating crossroads: a compound with deep cultural roots, a complex psychology, and just enough scientific backing to keep hope alive.
Reference:
Metaxa A-M, Clarke M. Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.BMJ 2024; 385:e078084. https://www.bmj.com/content/385/bmj-2023-078084