One Dose of Psilocybin, One Year of Follow-Up: What a Swedish Trial Tells Practitioners About Durability

Most psilocybin trials for depression stop measuring at six or twelve weeks. A randomized clinical trial from Karolinska Institutet in Stockholm, published in JAMA Network Open and brought back into wider circulation by science coverage this week, kept measuring for a full year. Its findings are a useful reality check for anyone considering, delivering, or training for psychedelic-assisted therapy: a single 25 mg dose of psilocybin was associated with rapid improvement in depressive symptoms, but by twelve months the gap between psilocybin and an active placebo had narrowed to the point of statistical insignificance.

Medically reviewed by Jacque Lovely, RN, MN, MBA, PMP, Reg #74334.

What the trial did

The study enrolled 35 adults with moderate to severe recurrent major depressive disorder who were in a current episode. None had used psychedelics before, and none were taking antidepressants or receiving psychotherapy when they entered the trial. Seventeen participants received a single oral 25 mg dose of psilocybin; eighteen received an identical-looking capsule of 100 mg niacin, chosen as an active placebo because it produces noticeable flushing and bodily sensations. Both participants and the raters assessing them were blinded.

Everyone, in both arms, received the same structured psychological support: a preparation session the day before dosing, a monitored dosing day lasting seven to ten hours with eyeshades, music and psychologists present, and three integration sessions on days 1, 8 and 15. The trial ran at the Northern Stockholm Psychiatric Clinic, with enrolment from January 2021 to February 2024, and is registered as NCT04630964.

The primary outcome was the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at day 8. Follow-up continued to day 365.

What it found

At day 8, the psilocybin group's MADRS scores had fallen about 7 points more than the niacin group's (a between-group difference of −7.27, 95% CI −12.89 to −1.65). The advantage was larger at day 15 (−11.03) and still present at day 42 (−8.33). On the self-rated MADRS-S, the difference appeared as early as day 2 and persisted through day 102.

Remission told a similar story. At day 42, 52.9% of psilocybin participants were in remission compared with 5.9% of the niacin group. By day 365, the psilocybin group's remission rate was unchanged at 52.9%, but the niacin group had climbed to 41.2%, and the clinician-rated difference between groups (−3.68) was no longer statistically significant. The authors link the placebo group's late improvement to the episodic nature of major depression and the possibility of spontaneous remission; a sensitivity analysis suggested antidepressant use did not explain it. Similar numbers in each group (six versus seven) started antidepressants during follow-up.

On safety, psilocybin was generally well tolerated. The most common treatment-emergent adverse events in the psilocybin group were headache, anxiety, hallucination, agitation, hypertension and paresthesia. Ten serious adverse events were recorded across the trial, none judged related to psilocybin. Two psilocybin participants, however, experienced severe anxiety that persisted for weeks after dosing and required medical attention.

Reading the result honestly

The authors' own conclusion is measured: a single dose "was associated with rapid antidepressant effects," and the findings "warrant further investigation into repeated dosing or adjunctive treatment strategies." That is the right register for practitioners too.

Three limitations matter. First, 35 participants is a very small sample; the trial could only detect large effects and was not designed to settle questions about long-term outcomes. Second, blinding largely failed. By day 365, 94% of psilocybin participants and all niacin participants guessed their assignment correctly, and the blinded rater guessed correctly for most participants as early as day 8. When outcomes are measured by interview and self-report, that kind of unblinding can inflate differences. Third, participants were recruited through social media and online advertising, which may have drawn people with high expectations.

None of this erases the early signal. It does mean the honest summary is "rapid, meaningful, and not obviously lasting on its own," rather than "one dose and done."

Why this matters for Canadian practitioners

In Canada, psilocybin-assisted therapy remains available only through clinical trials, Health Canada's case-by-case authorization initiated by a physician, or individual exemptions. The practitioners involved are working at the edge of the evidence and need to describe it accurately to patients and colleagues.

This trial supports several practical points. Set expectations around time horizons. The strongest evidence for a single session is measured in weeks to a few months; what happens at a year is uncertain, and this trial is one of the few to have looked. Patients deserve to hear both halves of that sentence. Plan for what comes after. The authors' call for research into repeated dosing or adjunctive treatment echoes what many clinicians already see: a psychedelic session is one component of care, not a replacement for ongoing treatment and follow-up. Take preparation and integration seriously. Both arms of this trial received five structured support sessions. Those sessions are the part of the protocol that nurses, psychologists, physicians and therapists actually deliver, and they are where training matters most. Prepare for difficult reactions. Two of seventeen psilocybin participants had anxiety lasting weeks. Screening, monitoring, and a clear plan for post-session distress are not optional extras.

It is also a reminder that durability is one of the live questions regulators are asking. The U.S. FDA's 2024 rejection of MDMA-assisted therapy cited insufficient durability data, and Health Canada will be weighing the same evidence as applications and trial authorizations move forward here.

The bigger picture

A single small Swedish trial does not change the field on its own. It adds a carefully run, placebo-controlled, year-long data point to a literature still thin on long-term follow-up, and it does so without overclaiming. That combination of rigour and restraint is the model to learn from.

If you are a healthcare professional considering psychedelic-assisted therapy training, ATMA CENA's Advanced Pathways are complete programs that begin with the Psychedelic Therapy Foundations course and build toward supervised practice. You can review the training options or book a conversation with a program advisor to talk through which pathway fits your background and goals.

Sources

1. Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression: A Randomized Clinical Trial. JAMA Network Open, 9(5), 2026.
2. A single dose of psilocybin eased depression within days, but its edge over placebo faded within a year. PsyPost, 2026.
3. Two Years After Rejection, Resilient Quietly Refiles MDMA for PTSD Application. Psychedelic Alpha, 2026.