A single dose of a psychedelic nasal spray helped reduce depression symptoms in people who did not respond to standard antidepressant medications, according to a clinical trial published in the medical journal JAMA.
The drug, called mebufotenin or 5-MeO-DMT, produces a short-lasting psychedelic experience.
Previous research cited in the study found that its effects peak within eight to 15 minutes and usually wear off within 45 to 60 minutes.
The clinical trial took place between September 2023 and April 2025 at 38 sites across Australia, Europe and the United States.
It included 193 adults aged 18 to 75 with moderate to severe depression who had not improved after treatment with two to five antidepressant medications.
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Researchers randomly assigned participants to receive a single nasal spray containing either 12mg or 8mg of the drug.
A third group received a very low dose of 0.3mg, which was not expected to produce noticeable psychedelic effects.
Researchers measured depression symptoms using a 60-point scale, with higher scores indicating more severe symptoms.
The main assessment was conducted on day 29, and participants were monitored for a total of 57 days.
By day 29, average depression scores had fallen by 11.1 points in the 12mg group and 12.5 points in the 8mg group.
The comparison group also improved, with scores dropping by an average of 5.5 points.
However, the two groups receiving the active treatment showed greater improvements than the comparison group.
The benefits appeared as early as the day after treatment and largely continued through the eight-week follow-up period.
Around one-third of participants who received the active doses experienced at least a 50% reduction in depression symptoms by day 29.
In comparison, this level of improvement was seen in only 12% of participants who received the very low dose.
Symptoms also fell to very low levels in 18% to 26% of participants in the active treatment groups, compared with 8% in the comparison group.
Side effects were common, but almost all were mild or moderate.
Headache, nausea and pain at the site where the spray was administered were the most frequently reported problems.
Researchers said larger trials with longer follow-up periods are needed to confirm the findings and determine how long the benefits last. – dpa
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