A Nasal Psychedelic Just Posted Phase 2b in JAMA. Most Patients Went Home Within Two Hours
A short-acting nasal psychedelic beat its comparator for treatment-resistant depression. The Phase 2b results published in JAMA on Monday. Most patients were cleared to go home within two hours. That second sentence is the one that matters to a clinic.
Whatever arrives next, the room and the staffing are what you are buying today. HealingMaps’ GPO, the first built for the ketamine industry, gets member clinics 40 percent or more off medical supplies, 15 to 20 percent off malpractice and liability premiums, discounted LegitScript certification, and 20 to 30 percent off HIPAA compliant payment processing. Joining is free with no obligation. See what your clinic qualifies for →
| Key Takeaway | Detail |
|---|---|
| The drug | Intranasal mebufotenin benzoate, a synthetic 5-MeO-DMT, developed as BPL-003 |
| The trial | Phase 2b, randomized, double-blind, 193 adults at 38 sites, September 2023 to April 2025 |
| The result | MADRS fell 12.5 points on 8 mg and 11.1 on 12 mg, against 5.5 on the comparator |
| Response at day 29 | 35 percent on 8 mg, 34 percent on 12 mg, 12 percent on the comparator |
| Discharge | 85 percent of the 8 mg group were ready to leave within two hours |
| The catch | The comparator was 0.3 mg of the same drug, not a placebo |
What the Trial Found
Participants were adults aged 18 to 75 whose depression had not responded to two to five antidepressant trials. Each received a single intranasal dose alongside psychological support.
Mean age was 41 and 59 percent were women. The primary endpoint was the change in Montgomery-Asberg scores from baseline to day 29.
The 12 mg group fell 11.1 points against 5.5 for the comparator. That is a difference of 5.3 points, with a confidence interval of 1.8 to 8.9. The 8 mg group fell 12.5 points.
Remission at day 29 reached 26 percent on 8 mg and 18 percent on 12 mg. The comparator reached 8 percent.
Adverse events were reported by 76 to 85 percent of participants across the dose groups. Nearly all of them, 99.7 percent, were mild or moderate. Full details sit in the PubMed record.
The Comparator Was Not a Placebo
This is the detail that will get lost in the coverage, and it cuts both ways.
The control group received 0.3 mg of the same compound rather than saline. That is deliberate. Patients can tell when they have been given a psychedelic, and a saline arm unblinds itself.
Using a low active dose is better science than pretending a blind holds. It is also why nobody should write that this drug beat placebo.
The comparator arm did behave close to one. A 12 percent response rate and 8 percent remission are in the range you would expect from an inactive control.
The Smaller Dose Did Better
The trial was designed around 12 mg, which carried the primary endpoint. The 8 mg group outperformed it anyway.
Eight milligrams produced a larger drop in depression scores and a higher response rate. Its remission rate ran eight points above the 12 mg group.
With 46 people in that arm, the difference is well inside the noise. But it is not a dose-response curve, and a Phase 3 will have to pick a dose.
Why Two Hours Is the Headline for Operators
The paper is explicit that monitoring time is the commercial problem it set out to solve.
Psilocybin sessions run most of a day. That constrains how many patients a certified room can see. We wrote about it in our piece on the race to shorten chair time.
Here, 85 percent of the 8 mg group were judged ready for discharge within two hours. The 12 mg group reached 78 percent. Assessment began at 90 minutes.
For a clinic, chair hours are the business. A treatment that empties the chair in two hours is a different throughput model. One that holds it until evening is another.
Read the Comparison Claims Carefully
The paper concludes the drug may require a shorter monitoring period and fewer clinic visits than psilocybin and esketamine, respectively. That word is doing a lot of work.
The shorter monitoring claim is against psilocybin. Spravato already requires two hours of observation, so this is not faster per session than esketamine.
The fewer visits claim is against esketamine, and it is the real one. Spravato runs twice weekly at the start. This was a single dose with effects still measurable at day 57.
Expect coverage to collapse those into one claim about beating both drugs at everything. It does not say that.
Who Ran It, and What Comes Next
Several authors are employees of AtaiBeckley and Beckley Psytech, which develop the compound. That is normal for an industry trial and it belongs on the record.
Lilly announced an agreement to acquire AtaiBeckley on July 16. The price was about $2.8 billion upfront, with milestones that could reach roughly $3.8 billion.
So the acquisition was announced before this peer-reviewed publication, on a trial that finished in April 2025. We covered the compound’s fast-track designation in October last year.
Phase 3 results are not expected until 2029. Nothing here is prescribable, and 5-MeO-DMT remains a Schedule I substance.
A Local Footnote
The first author is David Feifel of the Kadima Neuropsychiatry Institute in La Jolla. That clinic is listed in our own directory.
Trial sites are where this work actually happens, and some of them are practices our readers already know.
Clinics comparing their own market can start with our directory of verified ketamine clinics.
This article is for informational purposes and is not medical advice. Mebufotenin is not approved by the FDA for any indication. 5-MeO-DMT is a Schedule I substance under federal law, and the trial described here is Phase 2b.
