Frequently Asked Questions

In this 52-week observational follow-up, a single 25 mg dose of COMP360 psilocybin with psychological support was associated with a longer median time to a depression-related event than 1 mg. In the prespecified primary analysis of all COMP 001 participants, median time to first depression-related event was 92 days (95% CI, 49199) with 25 mg, 83 days (95% CI, 39142) with 10 mg, and 62 days (95% CI, 28NE) with 1 mg. The authors described the results as descriptive only, because the study was unpowered and no formal significance testing was performed.

The study defined a depression-related event as the first occurrence of any prespecified worsening or treatment change after baseline. These events included starting a new antidepressant treatment, hospitalization due to depression or suicidality, suicide attempt or prevention of an imminent suicide attempt, increased suicidality on MADRS item 10, worsening in MADRS total score, or discontinuation for an MDD-related adverse event or lack of efficacy.

• New antidepressant treatment could be pharmacologic, psychological, or somatic.
• MADRS worsening included either a rise of at least 5 points from baseline at any postbaseline time point, or a MADRS total score of at least 15 plus a rise of at least 5 points across 2 or more consecutive visits.
• Increased suicidality included a MADRS item 10 score of 5 or 6, or a score of at least 3 that increased by at least 2 points from baseline.

Yes. Among COMP 001 completers who entered the follow-up study, participants in the 25 mg group generally started new antidepressant treatment later than those in the 10 mg and 1 mg groups. At entry into COMP 004, which was 12 weeks after psilocybin administration, 27.3% (n=6) of the 25 mg group had started a new antidepressant treatment, compared with 47.4% (n=9) in the 10 mg group and 58.8% (n=10) in the 1 mg group.

By week 52, the proportion who had started a new antidepressant treatment was 54.5% (n=12) in the 25 mg group and 57.9% (n=11) in the 10 mg group, while the 1 mg group was numerically higher at 76.5% (n=13). The authors concluded that the 25 mg group tended to initiate new treatment later, although the study was descriptive and not powered for formal comparisons.

The most common depression-related events were starting a new antidepressant treatment and worsening MADRS total scores. Among all participants from COMP 001, initiation of new antidepressant treatment occurred in 48.1% (n=38) of the 25 mg group, 38.7% (n=29) of the 10 mg group, and 43.0% (n=34) of the 1 mg group. Worsening MADRS total scores occurred in 21.5% (n=17), 18.7% (n=14), and 22.8% (n=18), respectively.

Overall, the proportion of participants with any depression-related event was similar across groups: 54.4% (n=43) with 25 mg, 54.7% (n=41) with 10 mg, and 57.0% (n=45) with 1 mg.

The study results suggested that a single administration of COMP360 psilocybin was safe over 52 weeks in participants with treatment-resistant depression, with no new long-term safety signal identified. After entry into COMP 004, 61 treatment-emergent adverse events occurred in 27 participants, and the most common was COVID-19 in 13.8% (n=8). No participants experienced adverse events leading to study withdrawal or death.

Four treatment-emergent serious adverse events were reported by 3 participants after entry into COMP 004, and all were judged unrelated to study drug. The authors also reported that they did not observe persisting hallucinations consistent with hallucinogen persisting perception disorder.

Yes. Suicidal ideation was reported during long-term follow-up, but the serious adverse events that occurred after entry into COMP 004 were judged unrelated to study drug. One participant in the 25 mg group had a treatment-emergent serious adverse event of suicidal ideation and was hospitalized on study day 307. In the 1 mg group, one participant had 2 treatment-emergent serious adverse events involving therapy change requiring hospitalization due to moderate suicidal ideation.

A nonserious adverse event of mild suicidal ideation in the 1 mg group was reported as possibly related to study drug after entry into COMP 004. According to the report, that event began during COMP 001 on day 86 as moderate suicidal ideation, improved after COMP 004 enrollment on day 96, and resolved within 2 weeks.

This was a 40-week observational follow-up study that extended total follow-up to 52 weeks after COMP360 psilocybin treatment. It enrolled participants with treatment-resistant depression who had completed week 12 in the phase 2b randomized COMP 001 trial, and it also allowed enrollment from the phase 2 open-label COMP 003 study.

No further pharmacologic treatment or psychological support was provided during the follow-up study. For participants entering from COMP 001, blinding to the original treatment allocation was maintained through week 52, and depression severity was assessed remotely or in person using the MADRS by a blinded independent rater at prespecified follow-up visits.

The main limitations were the modest sample size, substantial censoring, and potential selection bias. Of the 126 COMP 001 completers who were offered enrollment into COMP 004, only 58 participants (46%) consented, and 45 completed the final COMP 004 visit. Because many eligible participants did not enter follow-up, 31.8% of participants from COMP 001 were censored at study completion in the primary time-to-event analysis.

The authors also noted that participants who entered COMP 004 were not fully representative of the full COMP 001 population at week 12, which limits interpretation of analyses restricted to follow-up enrollees. In addition, the study was unpowered, so no formal statistical comparisons between treatment groups were performed.

This study suggests that a single 25 mg dose of COMP360 psilocybin with psychological support may provide clinical benefit that lasts for some patients for up to about 6 months, while still leaving many patients needing additional treatment within a year. In the primary analysis, median time to depression-related event was 92 days with 25 mg versus 62 days with 1 mg, and by week 52 about half of the 25 mg group who entered follow-up had started a new antidepressant treatment.

The authors emphasized that these findings are descriptive and limited by low follow-up enrollment and lack of formal significance testing. Clinically, the results support follow-up planning beyond the acute treatment window and continued monitoring for relapse and suicidality.