Lea Mertens still remembers one participant from Mannheim who, months after a single psilocybin session, described feeling "like a stranger to his own sadness"—a moment that crystallized the potential of this therapy. Now, new findings from the EPIsoDE study, led by the Central Institute of Mental Health (CIMH), Charité–Universitätsmedizin Berlin, and the MIND Foundation, show that psilocybin combined with structured psychotherapy can produce meaningful, lasting relief for people with treatment-resistant depression—relief that holds for up to a year. This is the most comprehensive long-term follow-up of a psychedelic clinical trial to date, offering hope to millions who find little relief in conventional antidepressants.
Depression that resists standard treatments affects roughly one-third of patients, leaving them in prolonged distress. The EPIsoDE study enrolled 144 such individuals across Mannheim and Berlin between 2021 and 2024. All received at least one 25 mg dose of psilocybin within a carefully structured psychotherapeutic framework, including preparatory and integration sessions. Of these, 126 participants were followed at six and twelve months, offering an unprecedented window into the durability of psychedelic-assisted therapy.
The results are striking. Using the Hamilton Depression Rating Scale (HAMD17), researchers found that, on average, depressive symptoms remained about 8 points lower at the 12-month mark compared to baseline—a clinically significant improvement. Even more telling, this benefit persisted regardless of whether participants later resumed conventional antidepressants, suggesting the psilocybin experience itself contributed to sustained change. "Unlike traditional antidepressants, psilocybin is not taken continuously, but is used in just a few sessions alongside psychotherapy. This makes the results particularly remarkable," says Lea Mertens, the study’s first author.
Prof. Dr. Gerhard Gründer, head of the Department of Molecular Neuroimaging at CIMH, emphasizes the importance of long-term stability: "There is a great need for new treatment approaches that go beyond short-term improvements, especially in cases of treatment-resistant depression." The therapy’s structure—centered on integrating intense, often transformative experiences—appears crucial. Many participants joined optional monthly integration groups, a testament to the lasting psychological impact of their sessions.
Still, the team urges caution. This follow-up lacked a control group after the initial trial, and participants could resume standard treatments. Future randomized, long-term studies are needed to confirm these findings. Yet the message is clear: for some, a brief, profound experience may reset a long struggle. As research continues, the door opens to a future where healing isn’t measured in daily pills, but in moments that echo for months.