A single dose of psilocybin, administered with psychotherapeutic support, led to rapid relief from depressive symptoms, with effects sustained for over three months. The findings come from Sweden’s first randomised, double-blind clinical trial investigating a psychedelic substance for the treatment of depression, conducted at Karolinska Institutet and funded by Norrsken Mind.

Depression is one of the leading causes of disability worldwide and many patients do not respond sufficiently to existing treatments. Standard antidepressants such as SSRIs can also take several weeks to show effects and are often associated with side effects.

Psilocybin, a naturally occurring psychedelic compound found in ‘magic mushrooms’, has shown antidepressant effects in previous studies, particularly in treatment-resistant or cancer-related depression. In the current phase 2 study, published in JAMA Network Open, the researchers investigated whether psilocybin could also benefit people with a more common form of depression, Major Depressive Disorder.

The trial included 35 participants aged 20 to 65 with moderate to severe recurrent depression. Participants were randomly assigned to receive either a single dose of 25 mg of psilocybin or an active placebo consisting of niacin, a vitamin that produces noticeable physical sensations.

All participants received psychotherapeutic support on five occasions: before, during and after treatment. During the dosing session, participants wore eye masks, listened to music through headphones, and were encouraged to focus inwardly. 

The treatment effect was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), a widely used measure of depressive symptom severity. The measurements were taken by doctors who were blinded to the treatment on days 8, 15, 42 and 365 following dosing.

The primary outcome of the study was the change in depressive symptoms eight days after treatment. At this point, participants in the psilocybin group showed an average reduction of 9.7 points on the MADRS scale, compared with 2.4 points in the placebo group. The difference was statistically significant and is considered clinically meaningful. The effect persisted even after 15 and 42 days.

Participants also completed a self-report version of the MADRS. These showed an antidepressant effect as early as two days after treatment, with benefits persisting for just over three months compared to the placebo group.

After six weeks, 53 per cent of participants in the psilocybin group met criteria for remission, compared with six per cent in the placebo group. After one year, the same proportion of the psilocybin group remained in remission, although the groups no longer showed a statistically significant difference, as many participants in the placebo group had also recovered over time.

”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 the study’s lead author Hampus Yngwe, a PhD student at the Department of Clinical Neuroscience, Karolinska Institutet. He continues:

”However, the long-term effects are uncertain. Repeated treatments may be needed to prevent relapse. This needs to be investigated in larger studies.”

“The study marks an important milestone for psychiatric research in Sweden. The results add to a growing body of evidence suggesting that psilocybin-assisted treatments may become a valuable addition to mental healthcare, particularly for depression,” says Emma Christersson, Co-Managing Director of Norrsken Mind. 

“Several countries have already begun introducing psychedelic therapies in clinical settings. Now, Sweden must invest more in psychedelic research, professional education, and healthcare system preparedness to ensure the country is well positioned to adopt these treatments,” says Marcus Stråth, Co-Managing Director of Norrsken Mind. 

The treatment was generally well tolerated. Most side effects were mild or moderate and temporary. However, two participants who received psilocybin reported severe and persistent anxiety that required medical attention.

“It is important to emphasise 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.

Researchers also highlight ongoing methodological challenges in psychedelic research, as the substances produce strong and easily recognisable experiences. If participants and researchers can tell whether psilocybin or placebo was given, it becomes harder to separate the effect of the treatment from that of expectations. In the current study, almost all participants were able to guess which treatment they had received, which may have influenced the outcomes, according to the researchers.

“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.

The next step in the research project is to analyse data from the PET scans, as well as blood and cerebrospinal fluid samples collected before and after dosing. The aim is to better understand the biological mechanisms underlying psilocybin’s effects.

”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.

The study was conducted in collaboration between Karolinska Institutet and the Brain Stimulation Clinic within Northern Stockholm Psychiatry, Stockholm Region. The research was funded by Norrsken Mind and the Swedish Research Council. 

Publication: “Acute and Late Effects of Psilocybin on Symptoms in Major Depression: a randomised clinical trial”, Hampus Yngwe, Pontus Plavén-Sigray, Carl Johan Ekman, Eva Henje, Anders Berglund, Mikael Tiger, Maria Beckman, Johan Lundberg, JAMA Network Open, online 15 May, doi: 10.1001/jamanetworkopen.2026.12589 

For further information, please contact:
Marcus Stråth, Co-Managing Director Norrsken Mind
Email: marcus@norrskenmind.org 

Hampus Yngwe, PhD student
Department of Clinical Neuroscience, Karolinska Institutet
Email: hampus.yngwe@ki.se

Johan Lundberg, Professor
Department of Clinical Neuroscience, Karolinska Institutet
Email: johan.lundberg@ki.se

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About the Montgomery–Åsberg Depression Rating Scale (MADRS):

MADRS is used to assess the severity of depressive symptoms. The scale ranges from 0 to 60 points, with higher scores indicating more severe depression:

• 0–12 points: no depression or very mild depression 
• 13–19 points: mild depression 
• 20–34 points: moderate depression 
• 35–60 points: severe depression