Psilocybin, the primary psychoactive compound found in magic mushrooms, has shown potential in alleviating symptoms of depression for an extended period, even up to five years after a single dose, according to a recent study. This groundbreaking research was presented on June 18 at the Psychedelic Science 2025 conference in Denver, focusing specifically on patients diagnosed with major depressive disorder (MDD), commonly referred to as clinical depression. MDD is a serious mood disorder characterized by persistent sadness and a diminished interest in activities that were once pleasurable.
Currently, the most prevalent treatments for MDD include talk therapy and medications, particularly selective serotonin reuptake inhibitors (SSRIs). However, these traditional methods often require considerable time to exhibit noticeable benefits. In light of early indications that psilocybin might serve as an effective antidepressant, a team of researchers launched the first-ever randomized clinical trial aimed at evaluating the efficacy of this psychedelic substance in treating severe depression.
The clinical trial involved 24 participants, divided into two groups. One group received psilocybin at the beginning of the study, while the other group, referred to as the waitlist group, received the same dosage eight weeks later. All participants also underwent 11 hours of psychotherapy throughout the trial. Remarkably, the immediate-treatment group experienced a significant reduction in depressive symptoms compared to the waitlist group, as noted by study co-author Alan Davis, the director of the Center for Psychedelic Drug Research and Education at The Ohio State University.
At the conclusion of the four-week study, it was determined that psilocybin was approximately four times more effective than traditional antidepressants, based on previous research findings. One month post-treatment, 17 out of the 24 participants reported relief from depression symptoms, with 14 individuals reaching full remission. Additionally, patients exhibited a more rapid response to psilocybin than is typically seen with conventional antidepressant medications.
A crucial question remained: do the positive effects of psilocybin persist over time? Dr. Charles Raison, a professor of human ecology and psychiatry at the University of Wisconsin-Madison, highlighted the challenges of conducting long-term studies on psilocybin and depression, noting that participants often drop out or pursue alternative treatments that can muddle the results.
To explore the long-term impact of psilocybin therapy, researchers reached out to participants from the original trial several years later for a follow-up study. Out of the original participants, 21 agreed to enroll. Clinicians evaluated changes in their depressive symptoms from the time of the initial treatment to the present day. Participants completed a series of self-reported online questionnaires and met with clinicians to assess their daily functioning, levels of anxiety, and overall mental health.
The analysis revealed that 67% of participants who had experienced depression five years earlier remained in remission following just one session of psychedelic therapy. These individuals also reported lower levels of anxiety and improved daily functioning. Overall, two-thirds of the patients who benefitted from the treatment noted enduring positive changes in their mindsets, emotional health, and interpersonal relationships.
“I’m excited about these deeper aspects of their lives,” Davis remarked, emphasizing the significance of these psychedelic interventions beyond mere depression reduction. Many participants indicated that the treatment had prompted them to engage in self-reflection and therapeutic practices, aiding them in navigating life’s challenges.
Looking ahead, Davis expressed interest in conducting further studies to compare the effects of psilocybin and psychotherapy in the treatment of depression. However, he cautioned that the study’s small sample size and the discrepancy between initial findings and larger multi-site trials warrant careful consideration. In a larger trial involving 233 participants, only 37% of those who received a single dose of psilocybin combined with psychotherapy achieved remission from major depression.
Despite these variances, the findings reinforce the notion that psilocybin may indeed serve as an effective treatment for depression, and researchers are eager to determine how the results of multi-site trials will hold up over a five-year period following treatment.
