Psychedelic Nasal Spray Eases Treatment-Resistant Depression
A single dose of mebufotenin reduced depression symptoms in patients who had not improved on antidepressants, according to a clinical trial published in JAMA.
Updated on Nov. 13, 2026 in Mental Health
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A single nasal spray dose of mebufotenin, also called 5-MeO-DMT, reduced depression symptoms in adults who had not responded to two to five antidepressant medications. Results from the trial, which included 193 participants across 38 sites in Australia, Europe and the United States, were published in the medical journal JAMA.
Why it matters
Many people with moderate to severe depression do not improve after multiple antidepressant trials, leaving limited options for relief. The findings suggest a single treatment may offer a new approach for this group, though the researchers stressed that larger studies are needed before it can be considered for routine use.
In the randomized trial, about one-third of participants receiving active doses had at least a 50% reduction in depression symptoms by day 29, compared with 12% of those receiving the very low 0.3mg dose. Headache, nausea and pain at the spray site were the most frequently reported side effects, and researchers have not yet determined the durability of the effect.
The details
Participants were randomly assigned to receive either a 12mg or 8mg nasal spray of mebufotenin, or a 0.3mg comparison dose, and depression was measured on a 60-point scale. The drug produces a short-lasting psychedelic experience, and benefits first appeared by day one after treatment and largely continued through the eight-week follow-up period.
Timeline
September 2023: Clinical trial began across 38 sites in Australia, Europe and the United States.
April 2025: Clinical trial concluded.
Day 29: Main assessment of depression scores was conducted.
Eight-week follow-up: Benefits largely continued through the follow-up period.
Health Landscape
The results add a new candidate to the growing field of rapid-acting, single-dose treatments for depression that are being tested as alternatives to daily antidepressant medications. Because the findings come from a single trial with 193 participants, they represent an early signal that will require replication before shifting clinical practice.
For people with depression that has not improved on antidepressants, the trial suggests a single supervised treatment may be a future option, though it is not yet available outside research settings. Anyone considering such a treatment should discuss current evidence-based options with a qualified clinician.
The takeaway
The trial offers early evidence that a single dose of a psychedelic compound may relieve depression in people who have not responded to standard medications. Confirmation in larger, longer studies will be needed before any change in treatment is possible.
Further reading
Explore more on Mental Health to see how new depression treatments are being evaluated.
Source note: This article includes information reported by The Star.
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