At South Chesapeake Psychiatry, we pride ourselves on staying ahead of the curve when it comes to emerging treatments in mental health. A few months ago, I came across a LinkedIn post that introduced me to a compound I hadn't seen before: GM-2505 (also known as bretisilocin). The early data were striking, and as I looked deeper, I discovered that AbbVie had quietly invested in its development.
Then, on August 25, 2025, AbbVie made it official—announcing their intent to acquire GM-2505 from Gilgamesh Pharmaceuticals and advance it into late-stage clinical development. While GM-2505 remains investigational and is not yet FDA-approved, this move reflects growing confidence in its potential to reshape how we treat depression—especially in those with treatment-resistant symptoms.
GM-2505 is part of a growing class of fast-acting antidepressants. Unlike traditional SSRIs or SNRIs, which often take weeks to produce meaningful change, GM-2505 works via a dual mechanism: it is both a 5-HT₂A receptor agonist and a serotonin releaser, allowing for rapid onset of therapeutic effect. The goal is not just symptom relief—but symptom relief that happens fast, endures, and doesn’t require ongoing daily dosing.
In a recent Phase 2a clinical trial (n=40), participants receiving GM-2505 experienced a -18.5 point reduction in MADRS scores within 24 hours of the first infusion—a rapid and statistically significant change. By Day 14, the reduction deepened to -21.6 points, with 70% of participants reaching remission. By Day 29, that remission rate climbed to 94%—and the antidepressant effect persisted through Day 74 without any further treatment.
GM-2505 is administered via intravenous (IV) infusion, delivered in a monitored clinical setting. It has a relatively short duration of action: the psychoactive effects last approximately 60 to 90 minutes, and the compound has an elimination half-life of around 45 minutes. This makes it a practical option for in-office use, without the extended psychedelic experience associated with other 5-HT₂A agonists.
Dosing Regimen in Phase 2a
The dosing schedule used in the Phase 2a trial was simple:
Day 1: 10 mg (high-dose arm) or 1 mg (low-dose comparator)
Day 15: 15 mg (for both arms)
That’s it—just two infusions, two weeks apart. Participants were monitored for 74 days post-treatment, and the antidepressant effects remained consistent throughout the follow-up period.
GM-2505 was administered in a controlled, in-clinic two-hour framework, similar to what we use for esketamine (Spravato). Clients were continuously monitored, but no formal psychotherapy was required. Instead, support consisted of psychological check-ins, safety monitoring, and educational guidance. This approach potentially allows for greater scalability and accessibility compared to traditional psychedelic-assisted therapies.
Why This Matters
The current landscape of antidepressant options leaves many patients waiting weeks—or months—for relief. For those living with treatment-resistant depression, the stakes are even higher. A compound that works quickly, safely, and durably after only two sessions could radically change what we expect from psychiatric care.
Will Phase 3 Mirror Phase 2a?
Can you imagine the profound implications if this holds true—clients coming into a practice, receiving just two treatments, and potentially experiencing long-lasting remission or even a true cure? This possibility underscores how disruptive GM-2505 could be for the entire field of psychiatry.
It’s important to keep perspective when interpreting early results. Historically, Phase 2 trials—like the one GM-2505 has completed—tend to produce stronger effect sizes than Phase 3. Phase 2a studies are usually small, tightly controlled, and often exclude individuals with complicating comorbidities. In contrast, Phase 3 trials enroll larger, more diverse populations, which introduces more variability and often raises placebo response rates. As a result, the very high remission rates seen in early-phase studies often decrease somewhat in later-phase testing.
For example, esketamine (Spravato) showed striking early reductions in MADRS scores, but Phase 3 results were more modest, still significant but less dramatic. Similarly, Auvelity and psilocybin both demonstrated stronger signals in early-phase studies compared to their larger follow-up trials. This doesn’t mean Phase 3 fails—it just means results tend to normalize closer to real-world outcomes.
With GM-2505, even if remission rates drop from the remarkable 94% seen in Phase 2a to 55–65% in Phase 3, it would still represent a disruptive and significant leap forward compared to existing options. The durability of response after only two infusions is particularly promising, and if that signal holds—even at lower percentages—it could mark one of the most disruptive and meaningful antidepressant advances in decades.
At South Chesapeake Psychiatry, we are actively tracking the development of GM-2505 and other next-generation therapies. Should future data continue to support its safety and efficacy—and should FDA approval follow—we stand ready to thoughtfully integrate it into our practice.
Until then, we remain dedicated to delivering evidence-based, compassionate care using the best tools available today, while keeping our eyes firmly on the innovations of tomorrow.
Schedule an appointment today to get diagnosed, receive a prescription, and continue your journey towards mental peace.
