New Nasal Spray Shows Promise for Treatment-Resistant Depression

A fast-acting nasal spray containing a synthesized psychedelic compound derived from desert toads is showing promising results in clinical trials for individuals with treatment-resistant depression. The drug, mebufotenin (5-MeO-DMT), is being developed by AtaiBeckley, a subsidiary of Eli Lilly.

Rates of depression are historically high, with approximately one in six American adults experiencing the condition. A significant portion of these individuals, around 30%, have tried multiple medications without achieving adequate relief. While traditional treatments like therapy and standard antidepressants remain the first line of defense, emerging therapies, including ketamine, supplements like creatine, and even technology-based interventions, are being explored.

Clinical Trial Results

Researchers studied mebufotenin in a phase 2b clinical trial involving 193 adults aged 18 to 75 who had depression and had not responded to at least two prior antidepressant medications. Participants received psychological support throughout the study. The trial tested three different dosages of the drug.

Both the low (8 mg) and high (12 mg) doses demonstrated significant improvements in depression symptoms for over 34% of participants. The 8 mg dose showed the most pronounced effect, with a 12-point reduction in depression scores on a 60-point scale. Notably, a quarter of those receiving the 8 mg dose experienced remission of their depression after a single treatment, meaning their symptoms fell below a threshold for qualifying depression.

The benefits of the drug appeared rapidly, with symptom reductions observed between days 2 and 57. A key advantage highlighted in the study is the relatively short duration of the drug's effects, with most patients able to leave within two hours of administration. This contrasts with other psychedelic treatments like psilocybin, which can last over six hours, and even the FDA-approved nasal esketamine, which requires at least two hours.

Side Effects and Future Steps

Side effects were reported in a majority of participants, with 76% of those on the 8 mg dose and 85% on the 12 mg dose experiencing adverse events. However, nearly all reported side effects (99.7%) were classified as mild or moderate. Side effects were also noted at a low control dose of 0.3 mg, with 73% reporting adverse events. Common side effects included nasal discomfort, nausea, vomiting, headache, tingling sensations, and excessive saliva.

This phase 2b trial was designed to establish the safety and efficacy of mebufotenin. The drug must still successfully pass phase 3 trials, the largest phase of clinical testing, to gather sufficient evidence for regulatory approval before it can be made available to the public. Other psychedelic compounds, such as psilocybin and LSD, are also undergoing phase 3 clinical trials for depression treatment.

Mebufotenin is synthesized in a lab and does not involve harming any toads. The compound is chemically related to serotonin and is naturally found in the skin, venom, and eggs of certain toad species, particularly the Colorado River toad (Incilius alvarius).