Single Dose of Psilocybin Demonstrates Rapid Relief of Depression Symptoms in Phase 2 Trial

A single 25-mg dose of psilocybin produced rapid and clinically meaningful reductions in depressive symptoms among patients with major depressive disorder (MDD), according to findings from a randomized phase 2 clinical trial published in JAMA Network Open. The antidepressant effects were observed within days and persisted for more than 3 months in patient self-reports, further supporting growing evidence surrounding psychedelic-assisted therapy for psychiatric conditions.¹

Researchers from Karolinska Institutet conducted the double-blind, placebo-controlled study in 35 adults aged 20 to 65 years with moderate to severe recurrent MDD. Participants were randomly assigned to receive either a single oral dose of psilocybin (25 mg) or an active placebo of niacin (100 mg), alongside 5 psychotherapeutic support sessions over 17 days.^1,2

Rapid Symptom Relief Seen Within Days

The primary end point evaluated changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at day 8 following treatment. Investigators found that MADRS scores decreased by an average of 9.7 points in the psilocybin group compared with 2.4 points in the placebo group, representing a statistically significant between-group difference of 7.3 points favoring psilocybin.^1,2 Patient self-reported MADRS-S scores demonstrated improvement as early as day 2, with antidepressant effects persisting through approximately day 102.¹

Lead study author Hampus Yngwe, MD, MSc, consultant psychiatrist and PhD student at Karolinska Institutet’s Department of Clinical Neuroscience, said the findings suggest psilocybin could become an alternative option when rapid symptom reduction is needed.

“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,” Yngwe said.²

Traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs) often require several weeks before clinical benefits emerge, and many patients do not achieve remission. Investigators noted that the speed of response observed with psilocybin was comparable to ketamine and electroconvulsive therapy while potentially offering longer-lasting effects.¹

Long-Term Outcomes and Remission Rates

At 6 weeks, remission rates were substantially higher among participants receiving psilocybin. Approximately 52.9% of patients in the psilocybin group achieved remission compared with 5.9% in the niacin group.¹

Although differences between groups were no longer statistically significant at 1 year, psilocybin maintained superiority over placebo through day 42 on clinician-rated assessments and through more than 3 months on self-reported measures. Researchers suggested that repeated dosing or maintenance therapy may eventually be required to sustain long-term benefits.¹

“Repeated treatments may be needed to prevent relapse. This needs to be investigated in larger studies,” Yngwe said.²

The findings add to a growing body of research exploring psilocybin-assisted therapy across psychiatric and palliative care settings. In a recent Pharmacy Times article, investigators discussed evidence suggesting psilocybin may improve depression, anxiety, and existential distress in patients with life-limiting illness, particularly when paired with structured psychotherapy.³ Additional emerging research has also demonstrated potential benefits of psilocybin-assisted psychotherapy in substance use disorders, including cocaine use disorder, where treatment options remain limited.⁴

Despite growing clinical interest, psilocybin is not currently FDA approved for depression or other psychiatric conditions and remains classified as a Schedule I controlled substance in the US. Investigators recently noted that access to psilocybin outside of clinical trials remains highly restricted because of federal regulatory barriers, despite emerging evidence supporting its potential therapeutic role in psychiatric and palliative care settings.³

Safety and Pharmacist Considerations

Psilocybin treatment was generally well tolerated, with most adverse events classified as mild to moderate and transient. Common treatment-emergent adverse events included headache, anxiety, hallucinations, agitation, and hypertension.¹ However, 2 participants in the psilocybin group experienced severe and persistent anxiety requiring medical attention, emphasizing the need for careful patient selection and psychological monitoring.¹

“It is important to emphasize that the treatment is not risk-free and that some patients may need extra support,” said lead study author Johan Lundberg, MD, PhD, professor at Karolinska Institutet and the Centre for Psychiatry Research.²

For pharmacists, psychedelic-assisted therapies may eventually introduce new responsibilities involving medication screening, counseling regarding psychiatric risks, management of drug interactions, and coordination within multidisciplinary behavioral health teams if these therapies receive broader regulatory approval.

REFERENCES

1. Yngwe H, Plaven-Sigray P, Ekman CJ, et al. Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression. JAMA Netw Open. 2026;9(5):e2612589. doi:10.1001/jamanetworkopen.2026.12589

2. Karolinska Instituet. Single dose of psilocybin provided rapid relief from depression in new study. EurekAlert! Peer-Reviewed Publication. Published May 15, 2026. Accessed May 15, 2026. https://www.eurekalert.org/news-releases/1127987

3. Paquette A, Tolliday SL, Speer K, et al. Pathways to Psilocybin in Palliative Care. Pharmacy Times. Published May 14, 2026. Accessed May 14, 2026. https://www.pharmacytimes.com/view/pathways-to-psilocybin-in-palliative-care

4. Kariyawasam-Chavez R. Emerging Data Suggest Psilocybin May Benefit Patients With Cocaine Use Disorder. Pharmacy Times. Published May 8, 2026. Accessed May 14, 2026. https://www.pharmacytimes.com/view/emerging-data-suggest-psilocybin-may-benefit-patients-with-cocaine-use-disorder