Depression: Study Finds Rapid Improvement After a Single Dose Of a Psychedelic

What if a single dose of a psychedelic substance could alleviate symptoms of depression in just 48 hours? In a small clinical trial, researchers observed rapid improvement and benefits that persisted for months in some of the participants treated with psilocybin. These results open new possibilities for psychiatry, though further, larger-scale investigations into the efficacy and safety of this treatment are still required.

Depression can be a persistent and difficult-to-treat condition, especially when symptoms return even after various treatment attempts. For this reason, scientists are exploring alternatives that might produce faster and more lasting improvement.

One such possibility is psilocybin, a psychedelic substance that temporarily alters perception, emotions, and consciousness. A recent clinical study investigated whether a single dose could reduce symptoms in individuals with recurrent depression, that is, those who had already experienced multiple episodes of the disorder.

The study was conducted in Sweden and involved 35 adults diagnosed with moderate to severe depression. Participants were randomly assigned to one of two groups: one received a single 25-milligram dose of psilocybin, while the other received 100 milligrams of niacin, a form of vitamin B3, used for comparison.

Niacin was chosen as an active control because it can trigger physical sensations, helping to keep participants unaware of exactly which substance they had received. Furthermore, all participants took part in five psychotherapeutic follow-up sessions, during which they received guidance and support both before and after the administration of the substances.

To evaluate the results, the researchers used a scale called MADRS, which was developed to measure the severity of depression symptoms. By asking questions about aspects such as sadness, difficulty concentrating, sleep, appetite, and a loss of interest in life, the professionals assign a score that makes it possible to track each participant's progress.

The researcher in charge of the study, Dr. Hampus Yngwe. Credit: Photo: Stefan Zimmerman

Assessments were conducted before treatment and at various points afterward, including days 8, 15, 42, and 365. Participants also completed questionnaires regarding their own symptoms throughout the follow-up period.

The results showed a greater reduction in symptoms in the group that received psilocybin. According to the questionnaires completed by the participants themselves, this improvement was evident as early as the second day following administration.

In the primary clinical assessment, conducted on day 8, the psilocybin group also showed a significantly greater reduction in symptoms compared to the niacin group. The difference between the groups remained apparent in the assessments on days 15 and 42.

In the monthly questionnaires, the benefits were observed for more than three months, although they were not consistent at every time point. After one year, the difference between the groups was no longer statistically significant.

Although the results are promising, the researchers point out that the study involved a small number of participants and that improvement did not occur without difficulties for everyone. Most adverse effects were temporary and mild to moderate in intensity, but two participants experienced intense and persistent anxiety that required medical attention.

Therefore, these results do not mean that a single dose can cure depression, nor that the substance is safe to use without supervision. Further, larger-scale research is needed to determine its efficacy, its risks, and which patients might benefit from this type of treatment.

Lead researcher Dr. Johan Lundberg Credit: Photo: Stefan Zimmerman

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Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression: A Randomized Clinical Trial

Hampus Yngwe, Pontus Plavén-Sigray, Carl Johan Ekman, Eva Henje, Anders Berglund, Mikael Tiger, Maria Beckman, and Johan Lundberg

JAMA Network Open. 2026;9;(5):e2612589. DOI: 10.1001/jamanetworkopen.2026.12589

Abstract: 

 Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression

Visual Abstract.

Importance  Psilocybin has been proposed as a rapid-acting antidepressant (onset <2 weeks) with sustained effects (>6 weeks), but evidence from randomized clinical trials remains limited, particularly in the broader major depressive disorder (MDD) population.

Objective  To assess short-term and long-term antidepressant effects of psilocybin therapy in patients with MDD.

Design, Setting, and Participants  This double-blind, placebo-controlled randomized clinical trial of participants diagnosed with moderate to severe recurrent MDD was conducted at the Northern Stockholm Psychiatric Clinic between January 26, 2021, and February 19, 2024. Statistical analysis was performed from February 20, 2024, to June 20, 2025.

Interventions  Participants received a single dose of psilocybin (25 mg) or active placebo (niacin, 100 mg) and 5 psychotherapeutic support sessions during 17 days.

Main Outcomes and Measures  The primary end point was between-group difference in change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 8. Secondary end points included MADRS scores on days 15, 42, and 365, as well as monthly self-reports (MADRS-S) of depressive symptoms, disability, quality of life, and anxiety throughout the 365-day follow-up.

Results  The study included 35 participants (21 [60%] female; mean [SD] age, 41.0 [10.1] years) diagnosed with moderate to severe recurrent MDD, with 17 randomized to the psilocybin group and 18 to the niacin group. The study met its primary end point with a significant mean between-group difference (model estimated) in change in MADRS score on day 8 (−7.27; 95% CI, −12.89 to −1.65; P = .01) in favor of psilocybin. The between-group difference was significant also on days 15 (mean difference, −11.03; 95% CI, −16.65 to −5.42; P < .001) and 42 (mean difference, −8.33; −13.94 to −2.71; P = .004) but no longer on day 365 (mean difference, −3.68; −9.30 to 1.94; P = .20). For MADRS-S, the psilocybin group had a significantly greater reduction beginning at day 2 (mean difference, −9.58; 95% CI, −16.05 to −3.11; P = .004), with group differences persisting through day 102 (mean difference, −6.60; 95% CI, −13.01 to −0.19; P = .04) and then isolated effects at days 283 and 343. Most reported treatment-emergent adverse events were transient and of mild to moderate severity. No drug-related serious adverse events were reported. Two participants in the psilocybin group reported persistent, severe anxiety that required medical attention.

Conclusions and Relevance  In this randomized clinical trial of MDD, a single dose of psilocybin was associated with rapid antidepressant effects, observed by day 2 and persisting for more than 3 months on secondary outcomes; psilocybin was generally well tolerated, but some individuals required additional support after dosing due to anxiety. These results suggest that psilocybin may provide a rapid and relatively long-lasting antidepressant effect on major depressive disorder, warranting further investigation into repeated dosing or adjunctive treatment strategies.