Single dose of psilocybin linked to relief from symptoms of depression within days

Swedish researchers have reported that one 25 mg dose of psilocybin produced rapid, clinically meaningful reductions in recurrent depression symptoms, although the study also highlighted safety concerns and uncertainty over long-term benefit

A single dose of psilocybin has been shown to provide rapid and clinically meaningful relief from depressive symptoms within a few days, according to a first randomised, double-blind study in Sweden to assess the psychedelic compound as a treatment for depression.

A research team at the Karolinska Institutet, Stockholm, Sweden, has reported that the antidepressant effect persisted for more than three months in participants who received psilocybin. The phase 2 study assessed whether psilocybin could alleviate recurrent major depression. Cancer-related depression and treatment-resistant depression had been the subjects of previous research.

Depression is a major public health problem and can cause profound personal, social and economic harm. Selective serotonin reuptake inhibitors (SSRIs) remain among the most widely used treatments but they do not confer benefit to all patients. Their therapeutic effect can also take several weeks to develop and side effects are common.

Psilocybin, which is the psychoactive compound found in so-called ‘magic mushrooms’, has attracted increasing levels of research interest because previous studies have suggested that it may produce antidepressant effects after short courses – one or two carefully supported sessions – of treatment. However, researchers have also emphasised the need for robust trial designs to assess the true clinical effect and to account for the strong subjective experience produced by psychedelic substances.

The Swedish trial included 35 adults aged 20 to 65 with moderate to severe recurrent depression. Participants were randomly assigned to receive either a single 25 mg dose of psilocybin, or an active placebo in the form of niacin, a B vitamin that can cause a noticeable physical reaction – called a ‘niacin flush’ where there can be a red, hot flushing of the skin, often on the face, neck, chest and upper body which may look like sunburn. The placebo was chosen to help maintain blinding, although the researchers noted that psychedelic trials remain difficult to blind because the effects of psilocybin are often recognisable.

Both groups received psychotherapeutic support on five occasions before, during and after treatment. On the dosing day, participants were asked to lie down, wear an eye mask and listen to music through headphones while they focused inwardly.

The researchers measured treatment effects with the Montgomery–Åsberg Depression Rating Scale* (MADRS) a clinical scale used to assess the severity of depressive symptoms. Doctors who were blinded to the treatment allocation assessed participants on days 8, 15, 42 and 365 after dosing. To enter the trial, participants had to have been assessed to have a MADRS score of at least 22 points – it represents a point towards the lower end of the ‘moderate’ range in the evaluation of depression which scores from zero to 60.

The primary outcome was the change in depressive symptoms eight days after treatment. At this point, the MADRS score had fallen by an average of 9.7 points in the psilocybin group, compared with 2.4 points in the placebo group. This represented a group difference of 7.3 points in favour of psilocybin. The difference was statistically significant and the researchers considered it clinically meaningful. The effect also persisted at 15 and 42 days.

Participants also completed a self-report version of the MADRS. Their own assessments showed an antidepressant effect as early as day two, which persisted for just more than three months compared with the placebo group.

After six weeks, 53 per cent of participants in the psilocybin group were in remission, compared with six per cent in the placebo group. After one year, the same proportion of the psilocybin group remained in remission, but no confirmed difference between the groups was observed at that stage because many participants who had received placebo had also recovered.

“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,” said Dr. Hampus Yngwe, who is a consultant psychiatrist, and a doctoral candidate at the department of clinical neuroscience, Karolinska Institutet and lead author of the study.

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

The treatment was generally well tolerated. Most adverse events were mild or moderate and transient. 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,” said Dr. Johan Lundberg, professor at the department of clinical neuroscience and the centre for psychiatry research at the Karolinska and who led the study.

The researchers said that psychedelic treatment trials face important methodological challenges because the substances produce strong and easily recognised experiences. If participants and researchers can identify whether psilocybin or placebo was given, it becomes harder to distinguish the pharmacological effect from the influence of expectation. In the current study, almost all participants were able to guess which treatment they had received which may have influenced the outcomes.

“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,” said Yngwe.

The next stage of the research will assess positron emission tomography scan data, as well as blood and cerebrospinal fluid samples collected before and after dosing. The researchers aim to investigate whether psilocybin affects synaptic density in the brain.

“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 [see] whether psilocybin alters synaptic density in the brain,” said Yngwe.

* The Montgomery–Åsberg Depression Rating Scale ranges from 0 to 60 points, with higher scores to indicate more severe depression. Scores of 0 to 12 indicate no depression or very mild depression, 13 to 19 indicate mild depression, 20 to 34 indicate moderate depression and 35 to 60 indicate severe depression.

For further reading please visit: 10.1001/jamanetworkopen.2026.12589