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Psilocybin & Depression: See the Latest Science Here
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Recent studies indicate that psilocybin offers great promise as a depression treatment – particularly for individuals with treatment-resistant depression.
Depression is one of the leading mental health disorders worldwide, affecting more than 300 million people across the globe.
And for many, depression is so much more than a simple stretch of low mood. Depression can deeply disrupt quality of life1, intruding into relationships, appetite, sleep, self-worth, and the capacity to experience connection and joy.
Today, standard treatment for depression usually involves either counseling/talk therapy or pharmacological medications, primarily selective serotonin reuptake inhibitors (SSRIs), which aim to regulate serotonin levels in the brain.
Cognitive Behavioral Therapy (CBT) is often prescribed as a treatment for patients with depression. But it comes with significant limitations, with around 30–60% of patients experiencing relapse2 within a year after treatment ends.
Nowadays, experts like Dr. Gabor Maté advocate a more nuanced and positive approach to depression. For example, rather than pathologizing it, he sees it as an intelligent adaptation to childhood adversity or a society that leaves little room for authenticity and connection.
“The pain is there; when you close down emotionally in order not to feel the pain, you also close yourself off from feeling joy, from feeling connection, from feeling love.”
— Dr. Gabor Maté
Dr. Joanna Moncrieff highlights that depression is more complex than chemical imbalances or brain disorders even though brain scans show depression-related changes.
Dr. Moncrieff said: “It is always difficult to prove a negative, but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin.“
Psilocybin emerges as a potential solution to address the need for new depression treatments.
Multiple studies have demonstrated that psilocybin shows great promise as a depression treatment, particularly for individuals with treatment-resistant depression3 – when standard treatments have not provided any relief.
What is Psilocybin?
Psilocybin is the psychedelic compound found in what we commonly call magic mushrooms. Chemically, it’s known as O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine.
Psilocybin is a prodrug, which means it only becomes active after the body metabolizes it. Once consumed, psilocybin is converted into psilocin, which binds to serotonin receptors in the brain (particularly the 5-HT2A receptor).
This is what gives rise to its psychoactive effects, including shifts in perception, thought, and emotion that are commonly associated with a psychedelic experience.
The Swiss chemist Albert Hofmann officially isolated psilocybin in 1958 but psilocybin-containing mushrooms have been used by indigenous cultures throughout the world for spiritual and healing purposes as well as in ritual ceremonies for thousands of years.
The Science Behind the Healing
Psilocybin is structurally similar to serotonin, which is a neurotransmitter that plays a key role in regulating our mood, emotions, and feelings of well-being. Essentially, psilocybin works with the serotonin system, binding to the same receptors many antidepressants target, but does so faster.
Psilocybin appears to “reset” brain networks associated with depression. Research4 shows that psilocybin treatment leads to decreased amygdala CBF and increased resting-state functional connectivity in the default-mode network (DMN). DMN is the brain region linked to negative thought patterns and rumination. Psilocybin quietens the overactive DMN, and in this way offers hope for breaking the cycle of persistent negative thoughts and emotional distress that often accompanies depression.
At the same time, psilocybin increases brain network flexibility, or neuroplasticity5 and may therefore allow for new perspectives, emotional insights, and lasting shifts in mindset.
A 2023 article from the University of Utah Health6 points out that psilocybin seems to “wake up” the brain, allowing individuals to access suppressed emotions and reframe past traumas, especially when paired with therapeutic support.
A Closer Look at Clinical Research
There is a lot of buzz around psilocybin. But this buzz is actually backed by some rigorous clinical research.
One standout study from April 20217 directly compared psilocybin with escitalopram, a commonly prescribed SSRI. This double-blind, randomized controlled trial included 59 participants with moderate to severe depression. Thirty participants received two high doses of psilocybin (25 mg) spaced three weeks apart, while the other 29 received a small placebo dose of psilocybin along with a six-week course of escitalopram. Both groups also participated in around 20 hours of therapy to support the process.
The results were telling: both groups showed improvements, but those in the psilocybin group experienced faster and more significant relief from their symptoms, without the emotional numbing or side effects often associated with SSRIs. In fact, more participants in the psilocybin group reported that their depression had lifted, not just dulled.
In another study8, 27 participants with moderate to severe depression were treated with two doses of psilocybin in combination with supportive psychotherapy. After one year, participants showed significant decreases in depression symptoms, with improvements lasting well beyond the treatment period.
Another important trial, published in JAMA 9, involved 104 adults who were given a 25 mg dose of psilocybin along with psychological support. The results showed rapid and sustained antidepressant effects, with no serious adverse events reported.
Other key studies include the Johns Hopkins University’s 2016 study10, which demonstrated psilocybin’s ability to reduce depression and anxiety in patients with life-threatening cancer, establishing its potential for long-term mood improvement, and the Imperial College London’s 2016 study11 focused on treatment-resistant depression, showing psilocybin’s ability to provide meaningful benefits for patients who had not responded to other therapies.
It’s important to note that participants were almost always supported by therapy in these studies, which we can assume is a crucial component in the improvement of their condition.
Psilocybin vs. Traditional Antidepressants
Traditional antidepressants like SSRIs have helped millions manage depression. However, they often come with a range of side effects 12. Common short-term side effects include dizziness, sexual dysfunction, nausea, and headaches, with some lasting longer than expected.
In more severe cases, antidepressants can even increase suicidal thoughts13, especially in younger populations. Many also experience emotional blunting, where they feel numb or detached from their emotions. While this helps alleviate symptoms of depression, it also leads to a less joyous and connected life. Essentially, all emotions get dulled.
On the other hand, psilocybin seems to enhance emotional depth, supporting a more vivid and meaningful experience of life.
The Future of Psilocybin in Depression Treatment
Psilocybin’s promising results have already earned it “breakthrough therapy” status from the FDA, highlighting its massive potential to revolutionize depression treatment. There is growing optimism that psilocybin could become a mainstream option in clinical settings.
However, the future is not without challenges. The rejection of MDMA for PTSD treatment in August 2024 highlights the challenges on the path to widespread acceptance of psychedelics in the mental health field.
Despite these hurdles, psilocybin offers a promising alternative to traditional antidepressants, with its potential to reduce depression symptoms and create long-lasting healing, especially for those resistant to conventional treatments.
While continued research is crucial to ensure its safety, effectiveness, and optimal use, there is a lot of hope on the horizon.
Sources
[2] https://psychiatryonline.org/doi/10.1176/ajp.149.8.1046
[4] https://www.nature.com/articles/s41598-017-13282-7
[5] https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.724606/full
[7] https://www.nejm.org/doi/10.1056/NEJMoa2032994
[8] https://journals.sagepub.com/doi/10.1177/02698811211073759
[9] https://jamanetwork.com/journals/jama/fullarticle/2808950
[10] https://pmc.ncbi.nlm.nih.gov/articles/PMC5289681/
[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034394/
[12] https://www.psychiatrist.com/jcp/incidence-duration-side-effects-those-rated-bothersome/
[13] https://link.springer.com/article/10.1007/s00406-008-3002-1
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