Published in JAMA, the phase 2b trial found that a single dose of the psychedelic compound 5-MeO-DMT significantly reduced depressive symptoms, with most participants ready for discharge within two hours.
AtaiBeckley has reported promising results from a clinical trial investigating a short-acting psychedelic medicine for people with treatment-resistant depression.
The findings, published in the medical journal JAMA on 26 October 2026, suggest that a single dose of mebufotenin (5-MeO-DMT), delivered through a nasal spray, could provide lasting relief from depressive symptoms.
The phase 2b study involved 193 adults across 38 clinical sites in Australia, Europe and the United States. Participants received either an 8 mg or 12 mg dose of mebufotenin, or a much smaller 0.3 mg dose for comparison.
Both treatment doses produced significant improvements in depression symptoms, with benefits observed as early as two days after administration and continuing throughout the eight-week study.
Encouraging Results for Treatment-Resistant Depression
Treatment-resistant depression affects people who have not experienced sufficient improvement from conventional antidepressant medications.
In the AtaiBeckley trial, researchers measured changes in depression severity using a standard clinical rating scale.
After 29 days, approximately 35% of participants receiving the active treatment doses experienced a significant improvement in their symptoms, compared with 12% in the low-dose comparison group.
The study also reported remission rates of 26% for the 8 mg dose and 18% for the 12 mg dose, compared with 8% in the comparison group.
While both doses demonstrated antidepressant effects, the 8 mg dose appeared to offer a favourable balance between effectiveness and side effects.
A Shorter Psychedelic Experience
One of the most interesting findings was the relatively short duration of the treatment experience.
Unlike psilocybin, which can produce psychedelic effects lasting several hours, mebufotenin has a much shorter period of acute effects.
In the trial, 85% of participants receiving the 8 mg dose and 78% receiving the 12 mg dose were considered clinically ready for discharge within two hours.
However, the study required patients to remain under observation for at least four hours.
This could become an important advantage if the treatment eventually receives regulatory approval.
Longer psychedelic therapy sessions require extended supervision by trained healthcare professionals, which can increase costs and limit the number of patients clinics can treat.
A shorter treatment experience could make psychedelic-assisted therapy more practical to deliver, although further research will be needed to determine whether shorter monitoring periods are safe.
What Comes Next for AtaiBeckley?
The treatment was generally well tolerated, with most reported side effects considered mild or moderate. However, adverse events were common, and researchers emphasised the need for larger studies to better understand its safety.
The trial also followed participants for only eight weeks, meaning questions remain about how long the antidepressant benefits may last.
For AtaiBeckley, the findings provide further support for the development of BPL-003, its investigational nasal spray formulation of mebufotenin.
The company is pursuing a treatment that could offer meaningful antidepressant benefits without requiring the lengthy clinical sessions associated with some other psychedelic medicines.
Mebufotenin is not currently approved for treating depression, and larger phase 3 trials will be needed to confirm the results.
Nevertheless, the study provides encouraging evidence that short-acting psychedelics could have a role in future mental health treatment.
Source: Feifel D, et al. Single Intranasal Administration of the Psychedelic Mebufotenin for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA, 26 October 2026.
