A potential treatment for depression could one day come from toad venom causing trips. In a new study Wednesday, researchers appear to have deciphered the structural workings of a psychedelic compound derived from the Colorado River toad (Incilius alvarius). The team also tested a modified version of the compound in mice, finding it to have antidepressant and anti-anxiety effects, and potentially without psychedelic reactions that could complicate its safe use in humans.
Lately, psychedelics like LSD And psilocybin (the active ingredient in magic mushrooms) has received much scientific attention as a possible treatment for mental illness. Several clinical trials are currently testing these drugs for conditions such as depression, anxiety, and post-traumatic stress disorder. In June, outside experts affiliated with the Food and Drug Administration assess Phase III data on the use of MDMA-assisted psychotherapy for PTSD, and it is almost certain that a positive verdict will pave the way for FDA approval later this year.
As exciting as all of this is, there is still a lot scientists are trying to understand about how exactly these drugs work in the brain. Studies have find that the mind-altering effects of many popular psychedelics come largely from stimulation of a certain class of serotonin receptors found on brain cells, called 5-HT2A receptors, for example. But there are other types of 5HT receptors, as well as less-studied psychedelics that appear to activate them.
Researchers from Mount Sinai and Columbia University decided to take a closer look at one of these psychedelics, called 5-MeO-DMT. This compound is found in the venom of the Colorado River toad (the common nickname toad venom is a misnomer, because the venoms are injected into a victim via the fangs or other body parts). The drug is best known for its hallucinogenic and dissociative effects, while some user surveys have also suggested that 5-MeO-DMT may induce a rapid decline in symptoms of depression and anxiety. However, unlike some other psychedelics, 5-MeO-DMT appears to activate 5-HT1A receptors.
“We were intrigued by numerous reports of powerful, unique and revolutionary experiences associated with its ritual or experimental clinical use, which led us to question its therapeutic potential and the underlying mechanisms,” author of the study David Lankri, neuropharmacologist at the University of Chemistry. Department at Columbia University, told Gizmodo in an email.
The team studied 5-MeO-DMT using a variety of analytical methods, including cryogenic electron microscopy. This allowed them to confirm that 5-MeO-DMT activates both types of 5-HT receptors and to detail the exact structure of the compound.
From there, they created modified versions of it to better understand how it interacts with these receptors. They ultimately created a variant of 5-MeO-DMT that was much more potent at activating 5-HT1A and tested it in mice engineered to develop symptoms of depression and anxiety. In these mice, modified 5-MeO-DMT appeared to reliably induce antidepressant and anti-anxiety effects, and apparently without causing the typical psychedelic effects seen with the natural form.
“We showed that a selective compound, which almost entirely ‘ignores’ the psychedelic receptor, could be an effective treatment option for depression and anxiety,” Lankri said. The team’s conclusions were published Wednesday in Nature.
Studies like this represent only the beginning of our efforts to understand these substances. Additionally, other well-known psychedelics will likely be approved as mental health aids sooner than any treatments derived from 5-MeO-DMT or toad venom. As fun as an outing can be, the classic psychedelic symptoms of these drugs will likely limit their widespread prescription and use as medical treatments. Similar drugs without these effects, Lankri noted, they could probably be taken at home and would not require costly supervision from a trained clinician. It is also important to have more effective depression medications that work differently from each other, as some people will inevitably not respond to some of them.
Researchers are therefore hopeful about the potential of their research and the prospects it could lead to in the years to come. The team will continue to study 5-MeO-DMT, as well as the related drug ibogaine, which has also been shown to a promise as a treatment for depression and anxiety.
“It’s exciting to see detailed snapshots of the complex receptor dance induced by the psychedelic toad and its molecular descendants,” Lankri said. “This new knowledge could prove useful in the development of next generations of psychedelic-inspired medicines while revealing the beauty of the molecular world.”
News Source : gizmodo.com
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