The Sonoran Desert Toad (the Incilius alvarius, also known as the Colorado River toad or bufo toad) releases a poison through its skin that contains, inside, a psychedelic compound with therapeutic potential. The 5-MeO-DMT molecule, which is secreted naturally by the parotid glands of this amphibian, has hallucinogenic properties, causing temporary distortions of visual, auditory and time perception in those who consume it. But the trips generated by this compound can also have an impact on health and the scientific community is already investigating its properties to treat depression and other mental disorders. A study published this Wednesday in the journal Nature delves into the knowledge of this type of psychedelic and its medicinal possibilities: researchers from the Icahn Faculty at Mount Sinai in New York have mapped the molecular bases of 5-MeO-DMT in the brain and have analyzed how it interacts with the same receptor. serotonin used in other antidepressants. The research adds “crucial information,” its authors say, to facilitate the development of new neuropsychiatric therapies.
In the midst of a renaissance in psychedelic medicine, there are many eyes on the therapeutic potential of 5-MeO-DMT. And it is already being tested in humans with a handful of trials for resistant depression. But the mechanism of action, how this compound impacts the brain, remains unclear. Scientists are paying special attention to the interaction of this and other psychedelics with brain receptors that activate a key neurotransmitter for regulating mood: serotonin. This chemical substance serves as a communication route for neurons to send messages to each other and helps regulate various functions, from mood to digestion, temperature, sleep or sexual function. A low concentration of serotonin is associated with the development of depression and other mental disorders. Some conventional antidepressants, such as Prozac, precisely try to raise serotonin levels.
Daniel Wacker, author of the study published in Nature admits that what they know about the effects of 5-MeO-DMT “comes from anecdotal reports”: “The psychedelic induces altered states of consciousness, which are often described as trips and they cannot be compared to a high like that produced by cannabis. The trips They involve temporary distortions of visual, auditory and time perception, often described as hallucinations, but also so-called subjective effects that can range from pleasant mystical experiences and feelings of unity to negative experiences including fear, paranoia and vomiting. 5-MeO-DMT in particular has been associated with ego dissolution, that is, feelings of oneness with the universe, which could contribute substantially to the sustained antidepressant effects of psychedelics. However, this has not yet been demonstrated so far, and other studies, including ours, suggest that other mechanisms could also contribute to the antidepressant effects of 5-MeO-DMT2.
His research focused on analyzing, in animal models, how this compound interacts with a group of serotonin receptors closely related to anxiety circuits in the brain. “While there have been some studies indicating that other receptors could play a role in the actions of 5-MeO-DMT, the psychoactive effects of psychedelics have generally been attributed primarily to actions at the serotonin 5-HT2A receptor. 5-MeO-DMT has already demonstrated considerable therapeutic effects in humans, although these reports are anecdotal and cannot be equated with controlled clinical trials. Furthermore, the mechanisms by which 5-MeO-DMT and other psychedelics might treat psychiatric disorders are currently unknown. “Our studies suggest that for 5-MeO-DMT, binding and activation of the serotonin 5-HT1A receptor could play a critical role,” Wacker said in an email response.
Behind that alphanumeric nickname (5-HT1A) hides one of the 13 groups of receptors activated by serotonin and that “regulate numerous physiological processes, including many brain functions, intestinal motility and even the reproductive system,” explains the scientist. “5-HT1A is the most expressed serotonin receptor in the brain, where it regulates body temperature, memory and learning, mood, and other aspects of human physiology. Interestingly, 5-HT1A is the primary molecular target of several prescription antidepressants, including vilazodone, buspirone, and gepirone. 5-MeO-DMT binds to it pocket of 5-HT1A to which serotonin normally binds, but it interacts with the receptor differently compared to serotonin, as we demonstrate through atomic-level structures in our work,” he adds.
The researchers analyzed the interactions of the compound with these receptors and modified specific sites of the hallucinogen to evaluate, in mouse models of depression, its potential as a therapeutic agent. “Our studies provide crucial information on an understudied class of psychedelics and related compounds that may facilitate the development of new neuropsychiatric therapies targeting 5-HT1A,” the research concludes.
Víctor Pérez, who is head of Psychiatry at the Hospital del Mar in Barcelona and has a clinical trial underway (phase II) with 5-MeO-DMT for resistant depression, explains that Wacker and his team “propose what are part of the mechanisms of action”, but they do not resolve all the questions that remain in the air: “We do not know how the patient’s improvement occurs. There is a lot left to do and I don’t know if we will know what the final mechanism of action is. But it is striking that patients with depression that does not respond to individual treatments and are extremely desperate, after this therapy, within a few hours, make a qualitative change. [remite la sintomatología depresiva]. They are substances with tremendous power and, if you do it in the right places [bajo control sanitario]”They are quite safe drugs,” explains Pérez.
Clinical implications
Wacker’s findings shed a little more light to try to map, like in a movie, what happens in the brain when this psychedelic originating from the venom of the buffalo toad is used. But they also reveal the complexity of these mechanisms of action, admits the scientist: “Our research shows that the mechanism by which 5-MeO-DMT acts in the brain is probably more complex than previously assumed, since its effectiveness Clinic potentially depends on 5-HT1A and 5-HT2A receptors. “This finding could have clinical implications, as the drug could have known 5-HT1A-related side effects, as seen with other 5-HT1A drugs (sleep disorders, headaches, etc.).”
Regarding this study, Óscar Soto, president of the Spanish Society of Psychedelic Medicine, highlights that findings like these will allow “better identifying how [este compuesto] affects one receptor or another.” “It opens the door to developing new specific molecules to specifically bind to a specific receptor,” says the doctor, who has not participated in the research.
Soto is a psychiatrist at the Parc Sanitari Sant Joan de Déu, where three clinical trials have just opened to test 5-MeO-DMT and another psychedelic compound, psilocybin, in patients with resistant depression. Regarding the hallucinogen that was traditionally extracted from the venom of the bufo toad, Soto points out that it induces a process of brain plasticity and an altered state of consciousness “complex and different from other psychedelics,” but that it leads to “an acute improvement in symptoms.” . “A characteristic of altered states of consciousness is ineffability, the difficulty of describing that state: many people talk about feeling like they disappear, there are not so many visual alterations, but sometimes, they lose track of time. Sometimes you don’t even remember your own experience,” she says. He journey It is short, between 10 minutes and half an hour, but warns that “they are complex experiences and it is important that the patient feels safe and accompanied because it can be a difficult process to navigate.”
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