10
Loading video...
By Jasmine Laws
Reporter
0
Share
Newsweek is a Trust Project member
See more of our trusted coverage when you search.Prefer Newsweek on Googleto see more of our trusted coverage when you search.
A psychedelic—which comes from the venom of a toad—has been found to help people with treatment-resistant depression, a new study has found.
An international team of researchers found that the short-lived psychedelic called 5-MeO-DMT, which is derived from the venom of the Colorado River toad, could alleviate symptoms among people with depression who had previously exhausted other treatment options.
The psychedelic was administered to participants as mebufotenin benzoate nasal spray. The study was published in the journal JAMA on October 26 and funded by Eli Lilly.
Read More on Health
An Eli Lilly spokesperson told Newsweek: "Many people living with treatment-resistant depression have tried multiple treatments without lasting relief. These Phase 2b results for investigational BPL-003 showed that a single dose significantly reduced depressive symptoms, with benefit seen through the end of the eight-week study. We’re encouraged by these results and look forward to further evaluating BPL-003 in the Phase 3 program."
...
Alex Kwan, a professor of biomedical engineering at Cornell University, who was not involved in the study, told Newsweek that "it is a very strong set of data to show that intranasal mebufotenin can be useful for treatment-resistant depression. The study is well executed and rigorous."
The study builds on previous, smaller scale studies that also showed the potential of 5-MeO-DMT for treatment-resistant depression.
Albert Garcia-Romeu, a professor of psychedelics and consciousness at Johns Hopkins University, who was also not involved in this study, told Newsweek the results are "compelling because the shorter-acting effects of 5-MeO-DMT (lasting less than 2 hours) could help increase scalability and access to these treatments relative to other longer-acting psychedelics like psilocybin, which can take about six hours to administer."
What Is Treatment-Resistant Depression?
Treatment-resistant depression is defined by the U.S. Food and Drug Administration (FDA) as constituting an inadequate response to a minimum of two antidepressants, despite adequacy of the treatment trial and adherence to treatment.
Based on this definition, it has been previously estimated that at least 30 percent of those with depression have a treatment-resistant version of the condition.
Treatment-resistant depression has been associated with greater risk of various physical diseases, as well as increased costs because of higher intensity treatments and more health care utilization.
"Treatment-resistant depression is debilitating because the patients do not respond to current medications. Having another treatment option that is effective can be a game-changer," Kwan said.
What The Study Found
The study included 193 people with treatment-resistant depression, who were given either active or inactive doses of 5-MeO-DMT via a nasal spray. The trial was conducted in 38 sites across Australia, Germany, Poland, Spain, the U.K. and the U.S. for eight weeks.
The researchers said that most patients were able to be discharged within two hours of taking the drug.
"The drug is short-lived, but induces very intense subjective experiences in humans," Kwan said, adding that "other psychedelics like psilocybin and LSD are more advanced in clinical trials, but there is skepticism on how to deliver the drugs because they cause a relatively long 'trip.'"
Around a month after treatment, the researchers found that those who had taken the active version of the psychedelic saw marked improvements in their symptoms.
There were remission rates of between 18 and 26 percent at that stage, compared to 8 percent among those without the active dose.
Were There Any Side Effects?
Participants did commonly report adverse affects, but the researchers said these were "mostly mild or moderate." These adverse effects included headaches (almost 30 percent of participants experienced this symptom), nausea (around 24 percent) and administration site pain (around 16 percent).
They noted that no participants withdrew from the study because of these adverse effects, though 19 participants dropped out for other reasons.
Kwan said that the "one concern" about this study is that "many people reported transient effects after the treatment, although most were only headaches and nausea."
Garcia-Romeu also said that "as with most medications, this did not work for everyone—only about a quarter to a third of the patients who received the higher doses of the study drug showed a clinically significant response."
He also pointed to the side effects that were "undesirable in a small number of people," but added "that this is normal in medication development as we don't expect any treatment to be effective for everyone or to be free from side effects."
That said, he noted that researchers are still learning about the longer-term effects of 5-MeO-DMT, and pointed to a September 2026 study which found that in a participant group of almost 2,000 adults, adverse effects were frequently reported with 5-MeO-DMT use.
What The Findings Mean
At this stage, "the findings are interesting and suggest that down the line we may see new medicines like 5-MeO-DMT become available as new options to help people with treatment-resistant depression," Garcia-Romeu said. "However, more research will be needed to establish safety and efficacy, so for the time being, this won't be readily accessible to the general public outside of tightly controlled clinical trials."
He also said that the study sample was "relatively racially homogeneous, which means we'll need to see more data to ensure these types of effects generalize to other non-White samples."
He also said that "there was an element of psychological support involved in the treatment that can be difficult to disentangle from the observed effects, so it will be interesting to learn more about the relative contributions of the support vs. the medicine."
Reference
Feifel D, Seynaeve M, Cubała WJ, et al. (2026) Single Intranasal Administration of the Psychedelic Mebufotenin for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA. doi:10.1001/jama.2026.18380
Contact Newsweek editors on this story: Marc Vargas and Tony Phillips.
View 0 Comments
Submit Correction
View Editorial & AI Guidelines