COMP360 Psilocybin for TRD: What to Know Before a Possible 2027 Launch

COMP360, an investigational form of psilocybin, is undergoing a rolling New Drug Application (NDA) submission to the US Food & Drug Administration (FDA), with a projected launch in the first half of 2027 if approved. A recent analysis showed that patients with treatment-resistant depression (TRD) who responded but did not remit after a single dose of COMP360 psilocybin continued to gain benefit through week 26, with nearly 30% reaching remission after the second dose.1,2,3

The new data raises questions about how the treatment would be monitored, who is most likely to respond, and how it might be positioned alongside existing options for TRD. In this Q&A, Boadie Dunlop, MD, professor and chair of psychiatry and health behavior at the Medical College of Georgia at Augusta University, addresses what dosing-day supervision requires, how treatment resistance relates to response rates, and where COMP360 could fit relative to ketamine and esketamine. He also discusses the open questions investigators are still working to answer.

Dunlop's comments point to practical considerations for clinicians ahead of a potential approval, including staffing and monitoring demands, patient selection, and how to counsel patients on what the treatment involves. His perspective offers context for how COMP360 may be discussed with patients once regulatory decisions are made.

Psilocybin Dosing Day: Monitoring and Support Requirements

HCPLive: What does the monitoring and support structure look like for patients on dosing day, and how much of a barrier is that logistically for practices?

Dunlop: It's a barrier in the sense that you need to have someone available to respond to a patient who experiences adverse events or a distressing psychological experience. In the trials, there's a therapist in the room with the patient, and usually a second person available—sometimes in the room, sometimes watching by video. But you've got to be able to respond to the patient. Got to have someone available to respond to the patient for sure and help them get through difficult times, whether it's a physical side effect or a psychologically distressing experience.

When we talk about rollout, it's a barrier because you have to have someone who knows about this level of intervention or support that's required for many hours through the day—typically 6 or 7 hours in the case of psilocybin, which is why there's interest in shorter-acting treatments that might not require so long in the clinic before someone can go home.

How Clinicians Can Prepare for COMP360 Approval

HCPLive: With the rolling NDA submission underway and a projected launch in the first half of 2027, what should clinicians be doing now to prepare?

Dunlop: The main thing is reading the large trials. Most clinicians are not going to be administering this treatment. It's probably going to be done in specific centers, just like transcranial magnetic stimulation is currently done in specific centers, or esketamine treatment.

Most clinicians, though, need to be able to discuss with the patient the general pros and cons of what the treatment would involve. Understanding what's involved in preparation for it, the dosing, and then what support is needed after the dosing and the kinds of side effects that can occur and the probabilities of benefit.

It's about just reading the big trials that come out, the phase 3 trials…side effect risk factors [and] probability of response. There'll probably be a REMS, a monitoring system for safety after [approval].

HCPLive: What's the biggest limitation clinicians should know about who these treatments will and won't help?

Dunlop: The probability of benefiting from psychedelic treatments seems to relate to how treatment-resistant the individual is. People who don't have a high level of treatment resistance seem to respond at a much higher rate than people who are treatment resistant. But it's [the] people [who] are treatment resistant that we need [to help] the most because the options there [are] limited and…less positive.

HCPLive: How do you see COMP360 fitting into the treatment algorithm for treatment-resistant depression relative to existing options like ketamine or esketamine?

Dunlop: A big part is just going to be patient preference. The goal is to be able to lay out to the patient: these are steps that we can do beyond daily medication and present dosing and… risks and benefits. It's also going to depend on insurance coverage as well.

Ideally, you lay out the various option… and let the patient elect what they would rather pursue. Patient interest, motivation, [and] commitment [are] important to all of these treatments.

The idea that you would say, "Well, I think you really need to do transcranial magnetic stimulation next, and it's going to be a 30-day course of treatment where you come every day," may not be appropriate for an individual. They have to know what's best for them and their life.

HCPLive: What's the biggest open question you still want answered about COMP360—whether a longer follow-up in Part C or something else?

Dunlop: To me this is the big question: how much does a person need to have the altered mental state, induced by a psychedelic experience, in order for them to benefit from the treatment? Most of the research would suggest that's a key component for the great majority of patients to improve—to have a psychedelic experience.

The other side of the argument is that it's really about neuroplasticity, altered brain communication, network disruption and communication, and that there are efforts underway to develop drugs that do not induce a psychedelic experience but produce the same kind of biochemical changes in the brain that psychedelics do. That's the big question: how much? That's what I want to know.

In the short run, the bigger question is, what kinds of psychotherapy support are needed for people to most benefit from the treatment?

It's difficult because the company is looking to satisfy the FDA's expectations and requirements. Looking at what happened with MDMA and its approval process, there was a lot of concern about the variability and inconsistency of the psychotherapy that was provided. The industry is highly motivated to have standardized, relatively limited psychotherapy that's explicitly defined [and] that the FDA doesn't have to worry about altering the likely treatment outcome.

You can get a certain level of improvement if you just have minimal supportive monitoring of the patient during dosing and [do not do] any psychotherapy. But you might get additional benefits when you actually engage in a full psychotherapy model…in conjunction with the psychedelic experience.

That's going to be a huge, more short-term question to answer in the research over the next 1 to 2 years. Can we differentiate how much more a good psychotherapy experience adds to psychedelic dosing beyond just a simple supportive model, as is being done in the COMP360 trials?

Check out the new COMP360 data, along with a video interview with Dunlop, here: What New 26-Week COMP006 Data Mean for TRD, With Boadie Dunlop, MD

Editor’s note: Reported disclosures for Dunlop include Otsuka Pharmaceutical Development & Commercialization and LivaNova USA.

References

1. Compass Pathways. Compass Pathways Announces Six-Month Data From Second Phase 3 Trial Confirming Rapid And Durable Profile. Compass Pathways. July 7, 2026. Accessed July 16, 2026. https://ir.compasspathways.com/News--Events-/news/news-details/2026/Compass-Pathways-Announces-Six-Month-Data-from-Second-Phase-3-Trial-Confirming-Rapid-and-Durable-Profile/default.aspx

2. Derman C. COMP360 Psilocybin Sustains Depression Benefit Through 26 Weeks. HCPLive. Published on July 7, 2026. Accessed on July 16, 2026. https://www.hcplive.com/view/comp360-psilocybin-sustains-depression-benefit-26-weeks

3. Dunlop B. What New 26-Week COMP006 Data Mean for TRD, With Boadie Dunlop, MD. HCPLive. Published on July 16, 2026. Accessed July 16, 2026. https://www.hcplive.com/view/new-26-week-comp006-data-trd-boadie-dunlop-md