Psilocybin Shows Long-term Promise for Depression Relief
DENVER—Recent research indicates that psilocybin, the main active ingredient in magic mushrooms, has the potential to reduce depression for at least five years following a single dose. This study was presented on June 18 at the Psychedelic Science 2025 conference in Denver and focused on individuals diagnosed with major depressive disorder (MDD), often referred to as clinical depression. This serious condition leads to ongoing feelings of sadness and a lack of interest in previously enjoyable activities. Traditional treatments for MDD typically include talk therapy and medications like selective serotonin reuptake inhibitors, but both can take time to show results.
With earlier studies suggesting psilocybin’s potential as an antidepressant, researchers launched the first-ever randomized clinical trial to examine its effectiveness in treating severe depression. The trial involved 24 participants; half received psilocybin at the study’s start while the other half, the “waitlist” group, received the same dose eight weeks later. Each participant also underwent 11 hours of psychotherapy.
Even within that brief timeframe, there was a noticeable decrease in depression among those who received immediate treatment compared to the waitlist group, according to study co-author Alan Davis, who leads the Center for Psychedelic Drug Research and Education at The Ohio State University.
After all patients completed the four-week study, psilocybin appeared to be four times more effective than conventional antidepressants, according to previous research. A month post-treatment, 17 participants experienced relief from symptoms, with 14 reaching full remission. This response was notably quicker than what’s typical for standard antidepressant medications.
But what about the longevity of these effects?
Few long-term studies of psilocybin and its impact on depression exist, noted Dr. Charles Raison, a professor at the University of Wisconsin-Madison who was not involved in this research. He remarked that conducting such studies is challenging as people often drop out or undergo various other treatments that may obscure the effects of the psychedelic.
To determine whether the benefits of psilocybin truly endure, researchers reached out to the original participants years later for follow-up. Of these, 21 patients opted in, and their mental health professionals assessed any changes in their depressive symptoms since the initial treatment.
The participants also completed a series of online questionnaires and met clinicians to discuss daily functioning, anxiety levels, and overall mental health. The researchers assumed that three patients who did not enroll for follow-up and three who didn’t complete the questionnaires likely had not maintained their remission.
Even considering that, the findings revealed that 67% of the participants who had struggled with depression five years earlier remained in remission after one psychedelic therapy session. They also reported reduced anxiety and daily functioning difficulties. Generally, those who responded positively noted lasting improvements in their outlook, emotional health, and relationships.
“I’m excited about the deeper aspects of their lives that really highlight the importance of these interventions beyond just lowering depression,” Davis expressed.
Many participants shared that after their original treatment, they pursued self-reflection and therapy to better understand themselves and tackle life’s challenges. Davis speculates that the psychedelic experience might spark a deeper therapeutic process and hopes to conduct future studies measuring the respective impacts of psilocybin and psychotherapy on alleviating depression.
However, Raison cautioned that the small sample size is a significant limitation, noting that the initial trial exhibited stronger antidepressant effects than larger studies have since indicated. In a separate multi-site clinical trial involving 233 participants, only 37% of those receiving a single 25 mg dose of psilocybin along with psychotherapy achieved remission from major depression.
While these larger trials indicate less extensive antidepressant effects, they still support the premise that psilocybin can be effective in treating depression. Davis is eager to see how findings from multi-site trials align after five years of treatment.
