Rates of depression are historically high. About one in six American adults suffer from depression, and 30 percent of them have tried multiple medications without getting the relief they need.
If the first-line treatments remain traditional therapy and antidepressants, others are causing a sensation, offering a different approach to the treatment of this disorder.
People treat their depression with everything from FDA-approved ketamine to gym supplement creatine to an EEG headset paired with a video game-style workout.
Now, new evidence suggests the next big treatment could be a fast-acting drug found in a desert toad.
It’s called bufotenin, a psychedelic compound that belongs to the same family as serotonin. It is found in the skin, venom and eggs of a few species of toads, particularly the Colorado River toad, aka Sonoran Desert toad or Incilius alvarius.
Kiss some toads
Drugmaker AtaiBeckley (which is owned by Eli Lilly) is studying a single-dose nasal spray formulation of the drug in clinical trials – currently in Phase 2b, with promising results.
To be clear, no toads were harmed in the making of these drugs. AtaiBeckley synthesizes the drug mebufotenin (5-MeO-DMT) in a laboratory.
Researchers studied the drug in 193 adults aged 18 to 75, all of whom had depression and had tried at least two antidepressants but did not experience enough relief.
They divided these participants into groups who received three different doses of the drug and provided them with psychological support before, during and after treatment.
Both low (8 mg) and high (12 mg) doses helped more than 34% of participants.
Those who took both doses saw significant improvements in their depression, although the 8 mg dose was most effective – a 12-point reduction in depression scores on a 60-point scale.
A quarter of people receiving the 8 mg dose experienced remission of their depression after just one treatment. This does not mean that he has been cured, but simply that the symptoms have fallen below a threshold that qualifies as depression.
The benefits came quickly and lasted for weeks. A reduction in symptoms occurred from day 2 to day 57.
Future treatment
A few other psychedelics are being studied to possibly treat depression in the future. Psilocybin, aka magic mushrooms, and LSD, are both in phase 3 clinical trials.
One advantage of mebufotenin is that most (78-85%) patients were discharged within two hours. Psilosybin, on the other hand, can last for more than six hours. For reference, the FDA-approved nasal esketamine, which is not a psychedelic, requires 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. Almost all reported events – 99.7% – were classified as mild or moderate.
Notably, side effects were significantly elevated even at the low control dose of 0.3 mg: 73% reported adverse events.
A 2024 study showed that the most common side effects of this drug were nasal discomfort, nausea, vomiting, and headache. Another showed tingling sensations and excessive saliva.
The latter study was a phase 2b trial aimed at establishing safety and effectiveness before larger trials. The drug is expected to pass Phase 3, the largest phase aimed at gathering evidence for regulatory approval before a drug hits the market.
Gn Health
