Could a Toad’s Psychedelic Venom Help Treat Psychiatric Disorders?

A modified psychedelic found in the venom of a poisonous toad could be an effective treatment option for depression and anxiety, a new study published this week in the journal Nature found.

Recent scientific research has shown the potential of psychedelics in treating conditions such as depression, anxiety, and substance use disorders. These substances are thought to interact with serotonin receptors. The majority of research on psychedelics has focused on a serotonin receptor called 5-HT_2A, with less effort focused on investigating the role of another serotonin receptor, 5-HT_1A, in the effects of these compounds. 

Dr. David Lankri, a researcher in the laboratory of Columbia Chemistry Professor Dalibor Sames, in collaboration with Dr. Daniel Wacker’s group at Icahn School of Medicine at Mt. Sinai in New York, investigated the mechanism by which the hallucinogen 5-MeO-DMT (found in the poison of the Colorado River toad and associated with intense psychedelic experiences) interacts with 5-HT_1A. The researchers examined the serotonin receptor’s structure in great detail and modified specific sites in the compound. The result was a highly 5-HT_1A-selective variant of 5-MeO-DMT that was then tested for efficacy in mice. In tests, the compound was found to produce similar antidepressant-like activity to ketamine. Importantly, this effect was accomplished without the hallucinogenic effects of the unaltered compound.

“We are excited to have identified a compound that has highly potent therapeutic effects while avoiding the “psychedelic receptor” 5HT_2A,” said Lankri

These findings provide clarity on the ways in which this type of psychedelic can modulate the receptors in the brains of mammals and suggest a potential avenue for the development of medications for neuropsychiatric disorders. Further research is needed to assess whether these findings might translate to humans. 

“5-MeO-DMT, which is sometimes referred to as the ‘god molecule’ has held our interest for many years due to its intense and unique subjective experiences, and more recently promising therapeutic signals in preliminary clinical studies,” said Sames. “We also arrive at MeO-DMT by breaking down another enigmatic psychedelic, named ibogaine, which holds remarkable promise in the treatment of opioid addiction, PTSD, and traumatic brain injury (TBI). These two molecules—5-MeO-DMT and ibogaine—provide a rich and fertile area for discovery of novel therapeutics.”

“We’re hopeful that the insights from our study and the ongoing research in our labs will prove useful in the development of the next generation of psychedelic-inspired medicines,” Sames said.

This story was adapted from a press release by the journal Nature.