Psychedelics are experiencing a renaissance in the psychiatric field. MDMA, LSD, psilocybin (active ingredient of hallucinogenic mushrooms) are used and tested to treat a long series of disorders such as post-traumatic stress, addictions, anxiety and depression. And today there is a new entry in the field of psychedelic psychiatry: mebufotenin, a substance extracted from the venom of an American toad (Incilius alvarius), also used as a substance of abuse in a (relatively uncommon) cocktail known as “bufo”. A recent clinical trial tested its antidepressant efficacy and safety in patients with resistant forms of depression, and the results published in Journal of the American Medical Association are more than encouraging: in the form of a nasal spray it proves capable of eliminating the symptoms in the majority of patients, in a short time, for a period of up to eight weeks on average.
Research on psychedelic molecules
The scientific community’s interest in psychedelic compounds is part of a line of research that aims to identify therapeutic alternatives for patients who do not benefit from common antidepressants. Mebufotenin, chemical formula 5-MeO-DMT, is an organic compound present in the glandular secretions of the toad Incilius alvarius, native to the Sonoran desert (on the border between the United States and Mexico), which acts on serotonin receptors in the central nervous system with a pharmacological profile characterized by a rapid onset and a shorter duration of hallucinogenic effects compared to other similar substances (a desirable characteristic in a drug).
The testing focused on the nasal spray formulation to facilitate administration and ensure controlled dosing in a clinical environment. The study involved 193 patients with resistant depression, a group characterized by a poor response to standard drug treatments such as selective serotonin reuptake inhibitors. Participants were administered the spray formulation under rigorously controlled conditions, monitoring both the clinical efficacy and safety of the treatment.
The results
During the observation sessions, the researchers recorded the participants’ emotional response and changes in symptoms at regular intervals. The acute psychedelic effects induced by the molecule manifested themselves quickly, in most cases allowing patients to leave the clinic where it was administered within a few hours, a logistical aspect of no small importance.
The data collected at the end of the monitoring indicate that a single administration or short courses of the nasal spray can relieve depressive symptoms for an average of about eight weeks. An advantage compared to daily pharmacological treatments, which however leaves open several questions regarding the need, or otherwise, for long-term maintenance interventions. The adverse events observed during the trial were predominantly mild or moderate, mainly linked to the acute phase of the psychedelic experience. However, the authors of the study point out that the clinical response may vary based on the individual characteristics of the patients and that further studies on larger samples are needed to confirm the stability of the benefits over time.
Despite the encouraging results, the use of substances derived from animal organisms entails greater regulatory and production standardization challenges than chemically synthesized molecules. The variability of natural compounds and the need to guarantee rigorous pharmaceutical standards represent problems to be overcome in view of the possible commercialization of the molecule on a large scale.