Scientists at the Karolinska Institute (Sweden) conducted a randomized clinical trial - that is, one in which participants are randomly assigned to treatment groups - to test how a single dose of psilocybin affects symptoms of depression. The results were published in the journal JAMA Network Open.
The trial involved 35 adults with moderate to severe recurrent depression - a condition in which episodes of low mood recur with intervals of improvement. The average age of participants was 41, and 21 of them were women. None had previously tried psychedelics or was receiving antidepressants or psychotherapy at the start of the study.
Participants were randomly divided into two groups: 17 people received 25 mg of psilocybin in a capsule, and 18 received a capsule with 100 mg of niacin (vitamin B3). Niacin served as an active placebo - a substance that produces noticeable physical sensations, such as hot flushes, to make it harder for participants to guess which drug they had received. The study was double-blind: neither the participants nor the physicians assessing their condition knew who was in which group. Both groups also underwent five sessions of psychotherapeutic support over 17 days.
Depression symptoms were assessed using the Montgomery-Asberg Rating Scale (MADRS) - a questionnaire completed by a physician - as well as a self-report version. On the eighth day after dosing (the primary outcome), scores on the clinician-rated scale in the psilocybin group improved by about 7 points more than in the niacin group. The advantage persisted on days 15 and 42, but by day 365 the difference was no longer statistically significant. On participants' self-reports, improvement in the psilocybin group appeared as early as the second day and persisted for more than three months (through day 102).
By the eighth day, remission (disappearance of symptoms) was achieved by 8 people in the psilocybin group and 2 in the niacin group, but this difference was not statistically significant. On day 42, remission was 53% versus 6%, and after a year, 53% and 41% respectively, meaning the difference had become so small that it could have been due to chance. The authors note that in the niacin group the proportion in remission rose from 12% to 41% over the year, which probably reflects the fluctuating course of depression, including the possibility of spontaneous improvement.
Psilocybin was generally well tolerated: side effects such as headache, anxiety and hallucinations were mostly temporary, and no serious adverse events related to the drug were recorded. However, two participants in the psilocybin group developed severe anxiety after dosing that lasted for weeks and required medical care.
The researchers conclude that a single dose of psilocybin was associated with a rapid antidepressant effect that, by secondary measures, was observed from the second day and persisted for more than three months. They also note the need for further study of repeated doses or combined treatment approaches.
Limitations include the very small sample (35 people), because of which only very strong effects could be detected, and the fact that the study was not designed to support firm conclusions about long-term effects. In addition, blinding largely failed: at the end of the study, 94% of participants in the psilocybin group and all responders in the niacin group correctly guessed what they had received, and the physicians assessing symptoms also in most cases correctly identified the group. Because depression was measured through interviews and self-reports, knowledge of the treatment could have influenced the assessments. Recruitment through social media may have attracted people with inflated expectations.
It is important to emphasize: this concerns a statistical association, not a proven causal relationship, and the results do not mean that psilocybin can be used for self-treatment.