What's Next for Psychedelics in Psychiatry? COMP360 and Beyond

Psychedelics as part of psychiatry have moved from clinical curiosity to late-stage regulatory pipeline, with treatment-resistant depression (TRD) emerging as a leading indication for investigational agents such as psilocybin, LSD, and 5-MEO-DMT. Across 2 statistically significant positive phase 3 trials, COMP360 (a synthetic psilocybin) has demonstrated rapid onset, significant durability, and reproducibility of effect in TRD.¹ Six-month follow-up data from the COMP006 trial are expected to further characterize the durability of this effect.² Beyond efficacy signals, questions remain regarding the potential therapeutic infrastructure—including psychotherapy integration, supervised dosing sessions, and potential risk evaluation and mitigation strategies—required to safely deploy these agents at scale. At the Southern California Psychiatry conference, Gus Alva, MD, DFAPA, discussed with Psychiatric Times the current state of psychedelic research, trial data, and potential challenges on the road to the first psychedelic approval.

Psychiatric Times: How do you see growing psychedelic research impacting psychiatry?

Gus Alva, MD, DFAPA: It's a brave new world, right? I think that there is a lot of stigma associated with different types of substances, including psychedelics. But a lack of rigor is what probably stirred the pot with psychedelics initially; I love the fact that we are being responsible about doing investigational trials in these drugs. We are trying to figure out whether psychedelic agents may actually help us with hitting a reset button and then getting somebody out of that default mode network—where they've just been constantly ruminating—and then getting that salience, getting a better network connectivity so that people can actually snap into their better selves. And that is about what psychedelics offer at the present time.

PT: Has any of the psychedelic trial data stuck out to you as most clinically interesting?

Alva: You know, it's exciting seeing information like what Compass just shared about COMP360. Specifically taking a look at the results from the COMP006 open label psilocybin trial, it showed there is an enduring benefit 6 months out which replicates what was noted in the double-blind trial with the COMP005 study. I'm one of the investigators that has helped out with those particular projects, so I've actually seen patients come in and receive the treatment and then subsequently have sort of a transformational change.

PT: Are there aspects of psychedelic treatment you foresee might be challenges to approval or widespread use?

Alva: One thing that might be challenging is psychedelic treatments needing to be anchored with psychotherapy and a trained therapist. There is also the lengthy duration of time required to actually supervise the individual receiving the treatment. So, it's an interesting setting in that we are going to be seeing changes with maybe a risk evaluation mitigation strategy that's built into the use of these agents. As things look though, Compass may actually be the first company that gets a green light to commercialize a treatment like this that could be transformational for patients.

PT: Are there different types of psychedelics or different types of patients who might achieve the strongest results?

Alva: It's interesting seeing the inroads because beyond psilocybin there's the active form of psilocin, there's synthetic MDMA, LSD, 5-MEO-DMT—there are a lot of different psychedelics that are being tested out right now. It’s also important to note that there may be certain characteristics in patients that are required for a psychedelic to work well. Especially because patients can go through a good trip or a bad trip with these types of treatments. And I think that part of what dictates a positive experience is the openness or curiosity that somebody might have about the treatment. So it is going to be really interesting taking a look at how we select patients and how we prime them into the potential benefit associated with agents like psychedelics.

Dr Alva is a board-certified psychiatrist and the Mood Disorders Section Editor for Psychiatric Times.

References

1. Kuntz L, Goodwin G. Phase 3 program investigating COMP360 psilocybin for treatment-resistant depression: breaking poster data from the 2026 ASCP annual meeting. Psychiatric Times. May 28, 2026. https://www.psychiatrictimes.com/view/phase-3-program-investigating-comp360-psilocybin-for-treatment-resistant-depression-breaking-poster-data-from-the-2026-ascp-annual-meeting

2. Compass Pathways announces six-month data from second phase 3 trial confirming rapid and durable profile. Press release. July 7, 2026. Accessed July 15, 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