A fast-acting nasal spray offers hope for hard-to-treat depression: study

Rates of depression are historically high. Roughly one in six American adults have depression, and 30% of them have tried multiple medications without getting the relief they need.

While the first-line treatments are still therapy and traditional antidepressant medications, others are making a splash, offering a different approach to treating this disorder.

People are treating their depression with everything from FDA-approved ketamine to gym supplement creatine and an EEG helmet paired with a video-game like training.

Now, emerging evidence suggests the next big treatment might be a fast-acting drug that’s found on a desert toad.

It’s called bufotenin — a psychedelic compound that belongs to the same family as serotonin. It’s found in the skin, venom and eggs of a few toad species, especially the Colorado River toad, aka Sonoran Desert toad or Incilius alvarius.

Kissing a few toads

Drugmaker AtaiBeckley (which is owned by Eli Lilly) is seeing a single-dose nasal spray formula of the drug through clinical trials — now in phase 2b, with promising results.

To be clear, no toads were harmed in the making of these drugs. AtaiBeckley synthesize the drug mebufotenin (5-MeO-DMT) in a lab.

Researchers studied the drug with 193 adults aged 18 to 75, all of whom who had depression and had tried at least two antidepressants but didn’t feel enough relief.

They split these participants into groups who got three different doses of the drug, and gave them psychological support before, during and after treatment.

Both the low (8 mg) and high dose (12 mg) helped over 34% of participants.

Those who took the two doses saw significant improvements to their depression, though the 8 mg saw the most — a 12 point reduction in depression scores on a 60-point scale.

A quarter of those on the 8 mg dose saw a remission of their depression after a single treatment. This doesn’t mean it was cured though, just that symptoms fell below a threshold for qualifying depression.

Benefits appeared quickly and lasted weeks. Reduction in symptoms appeared from day 2 to 57.

Future treatment

There are a few other psychedelics being investigated to possibly treat depression in the future. Psilocybin, aka magic mushrooms, and LSD, are both in phase 3 clinical trials.

One benefit of mebufotenin is that most (78-85%) of patients were able to leave within two hours. Psilosybin, on the other hand, can last over six hours. For reference, the FDA-approved nasal esketamine, which is not a psychedelic, needs at least two hours.

Side effects were common, with 76% of patients receiving the 8-mg dose and 85% receiving the 12-mg dose reporting adverse events. Nearly all reported events — 99.7% — were classified as mild or moderate.

Notably, side effects were significantly high even at the low control dose of .3 mg: 73% reported adverse events.

A 2024 study showed that the most common side effects of this medication were nasal discomfort, nausea, vomiting and headache. Another showed tingling sensations and excessive saliva.

This latest study was a phase 2b trial to establish safety and efficacy before larger trials. The medicine would need to pass phase 3, the largest phase to gather evidence for regulatory approval before any drug hits the market.