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From the Grateful Dead’s tour bus to the FDA’s approval queue, from “turn on, tune in, drop out” to potentially “take two doses and see me in a year,” this is the improbable journey of psychedelics in 2025. We now live in a world where a ketamine analog marketed by Johnson & Johnson could provide a template for deuterated versions of classic psychedelics to win FDA approval for major depressive disorder and generalized anxiety disorder.
For millions of patients, current treatments offer little relief. “SSRIs, on average, reduce depression scores by about two points versus placebo,” explained Doug Drysdale, CEO of Toronto-based Cybin, which has won FDA Breakthrough Designation for CYB003, a proprietary deuterated psilocin molecule. (Psilocybin is a prodrug that the body converts into psilocin).
This 2-point improvement stands in contrast to CYB003’s results. “In our phase 2 study, when we have moderate to severely depressed patients, their average MADRS (Montgomery–Åsberg Depression Rating Scale) scores were 33.” For context, a MADRS score above 20 is considered moderate depression, and a score over 34 is severe. At the 3-week primary efficacy endpoint, a single 12 mg dose of CYB003 resulted in a mean reduction of 14.08 points in MADRS scores compared to placebo (p=0.0005). In the 12 mg cohort, after two doses administered three weeks apart, 79% of patients were in remission (defined as a MADRS score ≤10) at 6 weeks. The results were even stronger with the 16 mg dosing: at the 12-month follow-up, patients who received two 16 mg doses exhibited a mean reduction of approximately 23 points in MADRS scores from baseline. All of these participants were classified as responders (≥50% reduction in MADRS score), and 71% achieved remission. (Note, Compass Pathways achieved only a 3.6-point improvement in their Phase 3 trial of psilocybin, as discussed below.)
Cybin is optimistic that its proprietary, second-generation psychedelic molecules can change this reality. By swapping a hydrogen atom for its heavier isotope, deuterium, the company can fine-tune how the molecule is metabolized in both CYB003 (deuterated psilocin) and CYB004 (deuterated DMT), creating more predictable durations and potentially fewer side effects.
Doug Drysdale
Supportive figures like HHS Secretary Robert F. Kennedy Jr. and a rumored White House psychedelics policy advisor are shaping this new era. “RFK Jr. has been very supportive. He’s also spoken to us directly, and he’s very supportive of this work,” said Drysdale. “And I think he’s also focusing on trying to accelerate access perhaps for veterans in the next 12 months or so.”
FDA Commissioner Marty Makary has also signaled a commitment to an “expeditious and rapid review” of psychedelic data. This growing top-down support suggests that after years of grassroots advocacy and scientific research, companies ready to prove their case with rigorous data are finally seeing institutional doors open.
The sector’s volatile dynamic
Yet the tough realities of biopharmaceutical development and the restrictions of psychedelics being Schedule I substances has, at times, tempered investor optimism. Berlin-based Atai Life Sciences, another major player that German billionaire Christian Angermayer co-founded, saw its stock plummet in early 2023 after a Phase 2a trial of PCN-101 (R-ketamine) for treatment-resistant depression failed to meet its primary endpoint. More recently, the FDA rejected Multidisciplinary Association for Psychedelic Studies (MAPS)-associated Lykos Therapeutics’ MDMA (also known as “ecstasy”) application for PTSD.
While Compass Pathways achieved a milestone in June 2025 as the first classical psychedelic to report Phase 3 data, the result was a modest 3.6-point improvement versus placebo. For context, one meta-analysis found the average treatment difference for the SSRI escitalopram was about 3.0 MADRS points.
Building on Spravato’s infrastructure
Still, Johnson & Johnson’s sleeper hit Spravato offers a template that classic psychedelics could follow. The ketamine analog saw years of sluggish sales after its 2019 approval while building the necessary infrastructure. Now, with a recent expanded FDA approval as a standalone treatment, the drug is accelerating toward blockbuster status, generating $780 million in the first nine months of 2024 alone. “It’s got some real traction now,” Drysdale observed. “I think it’s about a $1.3 billion sales run rate.” J&J is now referring to the drug as a “key franchise,” guiding to three to five billion annually.
Spravato’s financial success has also created infrastructure for a new mental health treatment modality. The drug’s growth has spawned a network of 3,000 certified treatment centers across the U.S., each equipped with observation rooms, trained staff and protocols for managing dissociative experiences, all requirements that will likely apply to psychedelic therapies.
“I do see that Spravato is a useful analog for psychedelics,” Drysdale explained. “The treatment locations are the same. The staffing and training is pretty much the same as we would need.”
For companies like Cybin, this means they can build on existing infrastructure. “Getting these sorts of treatments, these interventional, intermittent treatments established like that is very helpful for us in terms of getting the infrastructure ready,” he noted.
The key difference with classic psychedelics, Drysdale said, could lie in dosing frequency. While Spravato requires patients to visit clinics every two weeks, 26 times per year, Cybin promises something dramatically different: just two doses annually. “After two doses, we saw 75% of patients in remission,” Drysdale noted. Its phase 2 trial for CYB003 involved administering just two doses (either 12mg or 16mg) three weeks apart, yielding a 79% remission rate at six weeks for the 12 mg group. “So I think what we’ve got coming is likely to be more effective, larger effect size, but also more convenient for patients as well,” Drysdale said.
From nature to pharmaceutical precision
Drysdale differentiates the controlled, medical-grade compounds in his pipeline from substances found in nature: “Although these are active molecules in nature, they’re developed drugs. When you think about psilocybin, it comes from about 200 different species of mushrooms, and the concentration can vary by 100-fold. There’s massive variability in nature.”
The goal of pharmaceutical development, he explains, is to eliminate that unpredictability: “The synthesis we’re doing reduces variability. Of course, drug development involves also optimizing the dose and the dose protocol and the safety envelope around the patient, and also patient selection so at-risk patients don’t get access.”
Tailoring the psychedelic experience
The patient experience itself is another crucial consideration in developing these molecules. Different compounds create distinctly different psychological journeys, which may be better suited to the needs of distinct patients. “It may be that some patients prefer a kind of gentler, more mystical, less intense psilocybin experience, or others might prefer a more intense, more immersive DMT experience,” Drysdale noted.
The choice of compound also reflects therapeutic strategy. For anxiety disorders, the rapid onset of DMT may actually be advantageous. “Some patients can fight it. They can kind of fight getting fully immersed,” Drysdale explained. With DMT’s quick action, anxious patients have less time to resist the experience. And that drug profile could make the therapy more effective in such cases.
In Cybin’s Phase 2 psilocin study, patients reported their second treatment as more intense, likely because they knew what to expect and were able to let go more fully. This psychological element of surrender appears central to the therapeutic process.
The regulatory bottleneck
Despite the high-level optimism, Drysdale acknowledged that significant operational hurdles remain, chief among them the DEA’s classification of these compounds: “For research purposes at the moment, these are Schedule 1 compounds. It means that every site that touches the compound, whether it’s a lab manufacturing it or whether it’s a clinical site, they all have to have schedule one DEA licenses.”
This licensing requirement creates a bottleneck that varies wildly from state to state: “DEA is absolutely run locally from local offices, and the performance and the timelines differ from office to office,” Drysdale said. “In some cases, it takes three or four months for a site to get a license, which is holding up a site from getting started.”
With RFK Jr.’s support, Drysdale sees a path forward. “From our perspective, one of the most helpful things the FDA, DEA, or HHS could do is streamline the scheduling process for research,” he explains.
Filed Under: Psychiatric/psychotropic drugs
