A single dose of psilocybin produced rapid antidepressant effects in a small Swedish clinical trial, with improvements lasting for weeks.
A single dose of psilocybin, the psychedelic compound found in magic mushrooms, produced rapid improvements in depression symptoms in a small Swedish clinical trial. After six weeks, 53% of participants who received psilocybin were in remission, compared with just 6% of those given a placebo.
Some participants reported improvements within two days, and the antidepressant effects persisted for more than three months in self-reported assessments. The findings come from Sweden’s first randomized, double-blind trial of psilocybin for depression, conducted by researchers at Karolinska Institutet and published in JAMA Network Open.
Testing Psilocybin for Common Depression
Selective serotonin reuptake inhibitors (SSRIs) are among the most widely prescribed treatments for depression, but they can take several weeks to work, cause unwanted side effects, and provide insufficient relief for some patients. Previous research has suggested that psilocybin may act more quickly, although much of that work has focused on treatment-resistant depression or depression associated with cancer.
The new phase 2 trial investigated whether psilocybin could also help people with more common forms of recurrent depression. Researchers enrolled 35 adults between the ages of 20 and 65 who had moderate to severe symptoms. Participants were randomly assigned to receive either 25 milligrams of psilocybin or niacin, a vitamin used as an active placebo because it produces noticeable physical sensations.
Both groups received psychotherapeutic support across five sessions before, during, and after treatment. During the dosing session, participants wore eye masks, listened to music through headphones, and were encouraged to direct their attention inward.
Depression Symptoms Improved Within Days
Researchers measured depression severity using the MADRS (Montgomery–Åsberg Depression Rating Scale), with assessments conducted by clinicians who did not know which treatment each participant had received.
Eight days after treatment, depression scores had fallen by an average of 9.7 points in the psilocybin group, compared with 2.4 points in the placebo group. The 7.3-point difference was statistically significant and considered clinically meaningful. The advantage remained evident at assessments conducted 15 and 42 days after treatment, while participants’ own ratings indicated improvement as early as the second day.
“Our results suggest that psilocybin can provide rapid, clinically meaningful improvement in depression and may serve as an alternative to standard treatment when fast symptom reduction is important,” says lead author Hampus Yngwe, consultant psychiatrist and PhD student at the Department of Clinical Neuroscience, Karolinska Institutet.
Long-Term Effectiveness Remains Uncertain
Although the initial results favored psilocybin, the difference between the groups was no longer statistically confirmed after one year. At that point, 53% of participants in the psilocybin group remained in remission, but many people who had received the placebo had also recovered.
“However, the long-term effects are uncertain. Repeated treatments may be needed to prevent relapse. This needs to be investigated in larger studies.”
The findings suggest that a single supervised dose may provide relatively rapid symptom relief for some patients, but the small trial cannot establish how consistently those benefits will last or whether additional doses would improve long-term outcomes.
Side Effects and the Challenge of Blinding
Psilocybin was generally well tolerated, with most reported side effects being mild or moderate and temporary. However, two participants who received the psychedelic experienced severe, persistent anxiety that required medical attention.
“It is important to emphasize that the treatment is not risk-free and that some patients may need extra support,” says Johan Lundberg, professor at the Department of Clinical Neuroscience and the Centre for Psychiatry Research, Karolinska Institutet, who led the study.
Another limitation involved the difficulty of keeping participants unaware of their assigned treatment. Psychedelics produce distinctive psychological effects, and almost everyone in the trial correctly guessed whether they had received psilocybin or the placebo. Such awareness can influence expectations and make it harder to determine how much improvement comes from the drug itself.
“We want to understand how factors such as treatment expectations and lack of blinding affect the results, as previous studies may have exaggerated the treatment effects,” says Hampus Yngwe.
Investigating How Psilocybin Changes the Brain
Researchers are now turning to biological measurements collected during the trial to investigate how psilocybin might influence depression. Their next analyses will examine PET brain scans alongside blood and cerebrospinal fluid samples obtained before and after treatment.
One area of interest is synaptic density, which reflects the number of connections through which nerve cells communicate. Depression has been associated with disrupted communication between brain regions, while preclinical studies suggest that psychedelics may promote the growth of synaptic connections. Whether comparable changes occur in people receiving psilocybin remains an open question.
“Research suggests that the interaction between parts of the brain is impaired in depression and that this may be linked to changes in the connections between nerve cells, known as synapses. In preclinical studies, psychedelics have been shown to stimulate synaptic growth. We therefore want to investigate whether psilocybin alters synaptic density in the brain,” concludes Hampus Yngwe.
Reference: “Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression: A Randomized Clinical Trial” by Hampus Yngwe, Pontus Plavén-Sigray, Carl Johan Ekman, Eva Henje, Anders Berglund, Mikael Tiger, Maria Beckman and Johan Lundberg, , JAMA Network Open.
DOI: 10.1001/jamanetworkopen.2026.12589
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