Two of the most cited psilocybin trials ever run weren’t about depression at all. They tested psilocybin against anxiety in people with life-threatening cancer, and the results were extraordinary: roughly 80 percent of patients maintained clinically significant improvement six months after a single session, with an effect size the field rarely sees anywhere, a Cohen’s d exceeding 2.0. A new commentary in Neuropsychopharmacology, by Gerasimos Konstantinou and Stefan Kloiber, lays out that case and the mechanism behind it in detail. It also, without saying so directly, highlights something odd about where the money and the drug development pipelines have gone.
The numbers behind the claim
Beyond the two cancer-anxiety trials, the commentary cites a meta-analysis pooling six double-blind randomized trials and 528 patients, which found that acute anxiety triggered by the psilocybin session itself was transient, typically resolving within 48 hours. The underlying trials themselves tested psilocybin against an active placebo, a real comparator drug, not an inert sugar pill, a stronger test than many trials in this space have used, and the anxiolytic effect held up against it. Anxiety disorders are also, by most epidemiological measures, more common than major depression, and current treatment has barely changed in decades: SSRIs remain the default first-line option, the same class that’s dominated depression treatment too.
Why nobody is chasing this indication with psilocybin
Compass Pathways is pursuing treatment-resistant depression and, more recently, PTSD. Usona Institute is focused on major depressive disorder. Reunion Neuroscience is targeting postpartum depression. Anxiety itself is not being ignored, but the companies committed to it are running on different molecules entirely. Definium’s flagship program, two Phase 3 trials deep in generalized anxiety disorder with a positive August readout already in hand, is built on DT120, which is LSD. Helus Pharma’s HLP004, which posted positive Phase 2 data in generalized anxiety in March, is a deuterated DMT. Not one of the field’s most capitalized sponsors is developing psilocybin, the compound with the strongest and most consistent anxiety effect sizes in the literature, for a primary anxiety indication.
A plausible explanation, and why it isn’t fully satisfying
Part of the answer is probably structural. The strongest anxiety data comes from a specific, narrow population, people facing a terminal or life-threatening cancer diagnosis, a smaller and more logistically complex population to build a large registrational trial around than the general treatment-resistant depression population Compass and others have targeted. Generalizing that result to anxiety disorders broadly, generalized anxiety disorder, social anxiety, and the rest, hasn’t been tested with anywhere near the same rigor, and the paper is explicit that direct clinical evidence in anxiety disorders outside the cancer-specific population remains limited. That’s a real gap in the evidence, not just a gap in company strategy. But it doesn’t fully explain why the companies that did commit to anxiety built their programs around other compounds, leaving the molecule with the largest existing signal unclaimed.
What this means for how the pipeline gets read
A paper like this, in a journal that carries real weight with the psychiatric research and regulatory community, tends to get cited directly by sponsors scoping out a company’s next indication and by regulators trying to judge whether a proposed trial design is scientifically plausible. If a mid-sized or newer psychedelic drug developer wanted a differentiated position, instead of competing directly with Compass and Usona on depression, or joining an increasingly crowded MDMA-PTSD field, anxiety with psilocybin specifically is sitting there as an indication with real supporting data and no direct competitor using the same compound. Whether that’s an opportunity nobody has moved on yet, or a population and trial design nobody has found a workable path through yet, is the open question this paper leaves unanswered.
What the paper doesn’t establish
None of this confirms psilocybin works as an anxiolytic outside the specific, narrow population it’s been tested in most rigorously. The strongest effect sizes come from patients facing imminent mortality, a psychological context that may itself be doing real work in how the drug’s effects are experienced and measured, not something that automatically generalizes to someone with generalized anxiety disorder and no terminal diagnosis. The paper’s own framing, calling this an area of “open questions” and not settled findings, reflects that limitation honestly rather than overselling it.