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The Science of Psilocybin for Depression

Game-changing new science for an incredibly important problem

By Austin Perlmutter, MD



  1. Global Mental Health Crisis: Mental health disorders like depression and anxiety affect hundreds of millions worldwide, with current medications like SSRIs failing to induce remission in about one-third of patients with major depression (MDD), necessitating evaluation of novel treatments like psilocybin.

  2. Historical and Recent Psychedelic Research: Psychedelics, including psilocybin, have been used for millennia and recent studies show they affect brain-related pathways, offering increased neuroplasticity and promising management for mood disorders with fewer side effects compared to traditional treatments.

  3. Psilocybin's Impact on Depression: Significant studies, including influential research from Johns Hopkins University, indicate that psilocybin therapy, paired with psychotherapy, leads to rapid and sustained reductions in depression scores, showcasing its potential as a groundbreaking treatment for MDD.

  4. Legal and Research Landscape: The promising results of psilocybin therapy are influencing global decriminalization trends and increased availability for therapeutic use, with ongoing research and trials, such as those supported by, driving forward the potential of psychedelics in mental health care.


When it comes to the most important health issues experienced in the world today, mental health must be at the top of the list. Mental health disorders like depression and anxiety affect hundreds of millions of people around the world. And despite the best that modern medicine has to offer, we have not seen that existing medications offer the types of benefits (especially for depression) that many of us have hoped for. This is a major why research into psychedelics has been so interesting and impactful.


Background on depression


Major depression affects around 300 million people around the world. Current antidepressants, such as SSRIs (selective serotonin reuptake inhibitors), are not effective for all individuals. Approximately one-third of patients with MDD do not achieve remission with existing medications. A high proportion of those taking conventional antidepressant experience side effects and withdrawal symptoms on discontinuation of the drugs.


Background on psychedelics


Psychedelics have been historically used for thousands of years. While many have moral or other opinions on the use of these molecules, they have been shown to have benefits to many brain-related pathways including an increase in neuroplasticity. Recent studies indicate that several psychedelics and related molecules including MDMA, psilocybin and ketamine show promise for management of mood disorders and other psychiatric issues with lower rates of side effects. Most classic psychedelics (this includes LSD, psilocybin and DMT) are believed to act through the serotonin system, but it’s now also understood that pathways like immunity and metabolism are involved.

Psilocybin for depression


One of the more consistent themes in psychedelic research concerns the use of psilocybin for major depression. In 2020, one of the most influential articles on psychedelics was published by researchers at Johns Hopkins University. This study explored the effects of psilocybin on people with depression, and the results were nothing short of remarkable.


In this study, the 24 participants were aged 21 to 75 years and diagnosed with major depression (MDD). They were not on antidepressant medications and had no history of psychotic disorders or serious suicide attempts. They were randomized into two groups: immediate treatment and delayed treatment (waiting list control). The intervention included two psilocybin sessions combined with supportive psychotherapy.


The immediate treatment group showed significantly lower depression scores compared to the delayed group, with large effect sizes. Additionally, a rapid decrease in self-reported depression was observed, which remained significantly reduced through the week 4 follow-up.


In subsequent larger studies, researchers have since shown similar results. One phase 2 study from 2023 looked at the impact of a single dose of psilocybin (versus a niacin placebo) on depressive symptoms. Those receiving the psychedelic had significant improvements in depressive symptoms as well as decreased disability scores.


What does this research mean?


Across the country and even across the world, many governments have moved to decriminalize and even make more readily available certain psychedelics for mental health. The research on psilocybin for MDD represents a dynamic and potentially transformative area of mental health treatment, offering hope for effective and rapid treatment for those suffering from one of the most common and debilitating mental disorders. It’s heartening to see the work now being done in Oregon to allow this potential game-changing therapy to be made more readily available to those best suited to benefit from it. If you are interested to learn more about current trials using psychedelics, consider exploring the work of the Multidisciplinary Association for Psychedelic Studies at


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