UN-STUCK –
Jan. 18, 2026 – Today, the key scientific and regulatory question is shifting away from if psilocybin could produce major durable improvements in depression and anxiety—because we’ve already come close to establishing, yes, it can—to whether benefits can be delivered affordably and safely.
What about hallucinations? Getting rid of depression is great, but the person taking hallucinogens must spend hours with in-person professional guides, safe facilities, and long-term monitoring.
Psilocybin is therapeutically promising. Recent mechanistic and clinical milestones—such as Fleury and Nautiyal’s January 2026 report in Molecular Psychiatry on a potential “non-hallucinogenic receptor target” for psilocybin-like medicines, along with Joshua Siegel’s systems-neuroscience work in Nature, and Compass Pathways’ late-stage clinical and FDA interactions—together outline a credible pathway toward psilocybin’s approval and next-generation, potentially non-hallucinogenic ‘psilocybin-like’ therapeutics.
For the past decade, most discussions of how psilocybin works have centered on serotonin 2A (5-HT2A) receptor activation; however, that’s also the principal driver of hallucinogen effects. If all hallucinations come from 5-HT2A, we might be able to reduce or remove 5-HT2A, but then we might also remove or diminish the therapeutic benefit. New research seeks to identify molecular and circuit targets in the brain that contribute to mood benefits, yet are independent of hallucinogenic signaling. And after that identification, the goal is to create drug candidates meeting those targets.
