When Johannes Reckweg moved to the Netherlands in 2016 to study in a master's program in neuropsychology, he had no idea that his research would lead to the discovery of a psychedelic substance most commonly found in a toad on the other side of the world. However, his interest in stimulants soon led him to 5-MeO-DMT, a substance that quickly gained his attention.
«This sparked my interest in pharmacological and psychopharmacological research and how drugs affect human behavior» — shared Reckweg Johannes, a PhD candidate at the Department of Neuropsychology and Psychopharmacology at Maastricht University.
This natural hallucinogen is found in some plants and mushrooms, but its best-known source is the Sonora desert toad, a greenish-gray amphibian found in the southwestern United States and northwestern Mexico. To obtain the psychoactive substance, poachers squeeze milk toxin from the toad's glands, which contains 5-MeO-DMT and other molecules. Although toads generally survive the procedure, environmentalists warn that the growing interest in this previously little-known compound is jeopardizing toad populations already suffering from climate change, habitat loss and disease.
«This sparked my interest in pharmacological and psychopharmacological research and how drugs affect human behavior» — shared Reckweg Johannes, a PhD candidate at the Department of Neuropsychology and Psychopharmacology at Maastricht University.
This natural hallucinogen is found in some plants and mushrooms, but its best-known source is the Sonora desert toad, a greenish-gray amphibian found in the southwestern United States and northwestern Mexico. To obtain the psychoactive substance, poachers squeeze milk toxin from the toad's glands, which contains 5-MeO-DMT and other molecules. Although toads generally survive the procedure, environmentalists warn that the growing interest in this previously little-known compound is jeopardizing toad populations already suffering from climate change, habitat loss and disease.
Amid the global resurgence of psychedelics as therapeutic agents, scientists are actively researching and developing synthetic forms of 5-MeO-DMT to treat hard-to-treat mental health disorders such as depression, anxiety, and post-traumatic stress disorder. While laboratory formulations are unlikely to eliminate recreational users of toad toxin, preliminary studies suggest that 5-MeO-DMT may have significant medical value, although more research is needed.
If the compound proves effective, its fast and powerful effects could make it a more affordable alternative to psilocybin and LSD, which take longer to act and are correspondingly more expensive.
Environmentalists warn that the growing demand for this previously undeservedly neglected psychoactive compound is having a negative impact on toad populations.
«There's a lot of interest in this area. I think we should slow this process down a bit to make sure we're acting with the right intentions and taking enough time to deeply understand what's going on» — said Anya Ragnhildstveit, director of research at Pneuma Science's Center for Psychedelic Research.
If the compound proves effective, its fast and powerful effects could make it a more affordable alternative to psilocybin and LSD, which take longer to act and are correspondingly more expensive.
Environmentalists warn that the growing demand for this previously undeservedly neglected psychoactive compound is having a negative impact on toad populations.
«There's a lot of interest in this area. I think we should slow this process down a bit to make sure we're acting with the right intentions and taking enough time to deeply understand what's going on» — said Anya Ragnhildstveit, director of research at Pneuma Science's Center for Psychedelic Research.
Rekweg emphasized that if research confirms that synthetic 5-MeO-DMT can alleviate symptoms of mental disorders, it would be an important treatment option worth considering. He also added that there is no one-size-fits-all drug, and some patients may not respond to certain psychedelics, but it is possible that they may respond favorably to 5-MeO-DMT.
The compound 5-MeO-DMT was first synthesized in 1936 by Japanese scientists Toshio Hoshino and Kenya Shimodaira — long before it was discovered in the toad. At the time, it was just part of research chemistry. They did not think about the psychoactive properties of the substance, as it was not relevant for the time. 5-MeO-DMT extracted from toads was first described in the mid-1960s, but it was a brochure published in 1983 that brought attention to the psychoactive compound and described how it was extracted, dried and smoked.
The big toad remained largely untouched until the twenty-first century. This changed in 2011 when Octavio Rettig, a self-proclaimed pioneer in the medical use of toads and a controversial figure, introduced the psychoactive substance to an indigenous tribe in the Mexican state of Sonora as a treatment for drug addiction among fishermen. The practice of smoking toad toxin spread quickly, accompanied by controversial accounts of its use by indigenous ancestors. Although toads occupy an important place in the mythology and iconography of some Mesoamerican cultures, it is not known whether they were used in traditional ceremonies precisely because of their psychoactive properties.
Lab formulas are unlikely to stop toad crushing enthusiasts, but limited research suggests that 5-MeO-DMT may have real medical value.
The compound 5-MeO-DMT was first synthesized in 1936 by Japanese scientists Toshio Hoshino and Kenya Shimodaira — long before it was discovered in the toad. At the time, it was just part of research chemistry. They did not think about the psychoactive properties of the substance, as it was not relevant for the time. 5-MeO-DMT extracted from toads was first described in the mid-1960s, but it was a brochure published in 1983 that brought attention to the psychoactive compound and described how it was extracted, dried and smoked.
The big toad remained largely untouched until the twenty-first century. This changed in 2011 when Octavio Rettig, a self-proclaimed pioneer in the medical use of toads and a controversial figure, introduced the psychoactive substance to an indigenous tribe in the Mexican state of Sonora as a treatment for drug addiction among fishermen. The practice of smoking toad toxin spread quickly, accompanied by controversial accounts of its use by indigenous ancestors. Although toads occupy an important place in the mythology and iconography of some Mesoamerican cultures, it is not known whether they were used in traditional ceremonies precisely because of their psychoactive properties.
Lab formulas are unlikely to stop toad crushing enthusiasts, but limited research suggests that 5-MeO-DMT may have real medical value.
Other countries also began imposing similar restrictions, leading modern researchers and recreational users of 5-MeO-DMT to seek opportunities in Mexico, where the use of the hallucinogenic toad poison is unregulated. In the U.S., the compound is still a Schedule I drug, which allows its legal use only for research purposes, and scientists need special permits to study the synthetic version.
In the Netherlands, where Rekweg first became familiar with 5-MeO-DMT at Maastricht University, he was interested in observational studies conducted in vivo, as well as reports from users who smoked the substance and reported positive effects on symptoms of depression, stress and anxiety.
One such study involving 24 participants showed an association between the intensity of psychedelic experiences and decreased depression and stress, as well as increased life satisfaction in smokers of natural toad venom. Although most participants did not have comorbid psychiatric disorders, those who reported having such disorders reported improvement. At the same time, the results of an anonymous online survey conducted in 2019 with 362 participants confirmed that the intense experience also helped reduce depression and anxiety.
Soon after, Reckweg began a controlled study of safety and psychedelic effects, becoming one of the first to conduct laboratory trials of synthetic 5-MeO-DMT in humans. He noted that the substance was understudied in the scientific community at the time.
One such study involving 24 participants showed an association between the intensity of psychedelic experiences and decreased depression and stress, as well as increased life satisfaction in smokers of natural toad venom. Although most participants did not have comorbid psychiatric disorders, those who reported having such disorders reported improvement. At the same time, the results of an anonymous online survey conducted in 2019 with 362 participants confirmed that the intense experience also helped reduce depression and anxiety.
Soon after, Reckweg began a controlled study of safety and psychedelic effects, becoming one of the first to conduct laboratory trials of synthetic 5-MeO-DMT in humans. He noted that the substance was understudied in the scientific community at the time.
In 2021, a study took place involving 22 healthy volunteers who inhaled different doses of the vaporized 5-MeO-DMT formula. Within 15-20 minutes, the participants experienced reactions ranging from peaceful sleep to active manifestations such as screaming and movement. These reactions are not uncommon, as the effects of the drug can be so strong that the participant loses consciousness or becomes vulnerable.
Because the drug causes strong emotional and physical reactions, clinical trials must adhere to strict safety standards. A safety doctor was always present in these studies and no medical intervention was necessary.
After the drug wore off, participants shared their experiences, describing «white hole» feelings or less vivid memories. This altered perception distinguishes 5-MeO-DMT from other psychedelics, such as DMT, which is associated with clearer and more vivid experiences, such as traveling into space or meeting otherworldly beings.
While the study confirmed the safety of administering the drug, a follow-up study in 2023 showed that vaporized synthetic 5-MeO-DMT reduced symptoms of treatment-resistant depression in 16 patients, and half of them experienced remission after one week.
Meanwhile, another group of scientists became interested in 5-MeO-DMT when they learned of a woman with suicidal tendencies who, after a single dose of the natural compound, experienced rapid relief from chronic PTSD that persisted for a year. Her story was then published in 2023 in Frontiers in Psychiatry, while withholding the woman's name to maintain confidentiality.
«She had tried virtually every traditional treatment available for PTSD — psychotherapy, medication, even cannabis. She had indeed done a lot, but nothing worked» — the authors write.
The compound also caught the attention of Lancelotta, who has conducted observational studies on the effects of both natural and synthetic forms of 5-MeO-DMT. The results of his research, published over the past five years, suggest that the synthetic compound may have a positive effect on people suffering from depression, anxiety and post-traumatic stress disorder.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7036074/
In a 2019 study conducted in the Czech Republic, where the compound 5-MeO-DMT is not strictly controlled, researcher Lancelotta observed its effects on a group of about twelve volunteers. Participants inhaled a vaporized synthetic version of the compound under the supervision of a facilitator in a yoga studio. Results showed «decreases in various biomarkers of stress and inflammation» and participants also noted increased life satisfaction after their experience with 5-MeO-DMT.
Lancellotta noted that one of the benefits of 5-MeO-DMT is its short duration of action, allowing for a deep mystical experience in a relatively short period of time. This greatly reduces time and cost for patients, especially when compared to other psychedelics such as psilocybin, which can last up to eight hours.
«She had tried virtually every traditional treatment available for PTSD — psychotherapy, medication, even cannabis. She had indeed done a lot, but nothing worked» — the authors write.
The compound also caught the attention of Lancelotta, who has conducted observational studies on the effects of both natural and synthetic forms of 5-MeO-DMT. The results of his research, published over the past five years, suggest that the synthetic compound may have a positive effect on people suffering from depression, anxiety and post-traumatic stress disorder.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7036074/
In a 2019 study conducted in the Czech Republic, where the compound 5-MeO-DMT is not strictly controlled, researcher Lancelotta observed its effects on a group of about twelve volunteers. Participants inhaled a vaporized synthetic version of the compound under the supervision of a facilitator in a yoga studio. Results showed «decreases in various biomarkers of stress and inflammation» and participants also noted increased life satisfaction after their experience with 5-MeO-DMT.
Lancellotta noted that one of the benefits of 5-MeO-DMT is its short duration of action, allowing for a deep mystical experience in a relatively short period of time. This greatly reduces time and cost for patients, especially when compared to other psychedelics such as psilocybin, which can last up to eight hours.
Charles Nemeroff, a physician and chair of the Department of Psychiatry and Behavioral Sciences at the University of Texas Medical School, said there are currently no studies that directly compare the effects of natural and synthetic forms of 5-MeO-DMT. The synthetic form allows for precise doses of the pure compound, giving more certainty about exactly what the patient is receiving.
Researcher Ryan Hahn, who works with Ragnhildstveit at Pneuma Science, emphasized that using synthetic 5-MeO-DMT in research could help better evaluate its therapeutic effects and gather the necessary safety and efficacy data for medical use. Several biopharmaceutical companies are currently developing and testing various synthetic formulations of 5-MeO-DMT in international clinical trials. Although the molecule itself cannot be patented, companies can protect their formulation developments for clinical use.
Earlier studies of 5-MeO-DMT have included small numbers of healthy participants or people with a variety of mental health symptoms, but new large-scale studies are focusing on the efficacy of the formulas for patients with diagnosed depression, especially in cases where therapy is difficult.
5-MeO-DMT research has evolved against the backdrop of renewed research on psychedelics over the past two decades, which has contributed to regulatory changes. In 2018, the US Drug Enforcement Administration simplified the application process for researching controlled substances for medical purposes. Public support for psychedelics in the U.S. is also growing, with a July 2023 poll showing that about 60% of voters support legalizing therapeutic access to psychedelics.
Researcher Ryan Hahn, who works with Ragnhildstveit at Pneuma Science, emphasized that using synthetic 5-MeO-DMT in research could help better evaluate its therapeutic effects and gather the necessary safety and efficacy data for medical use. Several biopharmaceutical companies are currently developing and testing various synthetic formulations of 5-MeO-DMT in international clinical trials. Although the molecule itself cannot be patented, companies can protect their formulation developments for clinical use.
Earlier studies of 5-MeO-DMT have included small numbers of healthy participants or people with a variety of mental health symptoms, but new large-scale studies are focusing on the efficacy of the formulas for patients with diagnosed depression, especially in cases where therapy is difficult.
5-MeO-DMT research has evolved against the backdrop of renewed research on psychedelics over the past two decades, which has contributed to regulatory changes. In 2018, the US Drug Enforcement Administration simplified the application process for researching controlled substances for medical purposes. Public support for psychedelics in the U.S. is also growing, with a July 2023 poll showing that about 60% of voters support legalizing therapeutic access to psychedelics.
Robert Conley, a psychiatrist and Beckley's chief scientific officer, notes that psychedelics such as 5-MeO-DMT have significant potential in medicine. The company's current trial follows earlier studies involving fewer than 20 participants and aims to assess the drug's tolerability and antidepressant effects.
The study, planned for late 2023, will include 225 people diagnosed with severe depression who will be administered a special saline formula through a nasal device. Participants will be closely monitored for six months after the dose is administered.
Despite the encouraging results, the approval process for medical use of 5-MeO-DMT could take years due to strict clinical trial requirements. Many researchers express hope that when 5-MeO-DMT is ready for medical use, its use will not lead to rampant use in mental health, as happened with ketamine. Lancellotta emphasizes that in a supportive setting, 5-MeO-DMT can provide short-term relief, but long-term results will require more than just administering the drug.
In the past three years, biologists Montaño Perez and Jauregui Santacruz have conducted research on the toad and its habitat and launched awareness programs. They are trying to dispel the myth that squeezing toad glands is harmless, emphasizing that it can cause stress to the animals and threaten their population.
Uncertainty also remains around synthetic 5-MeO-DMT: is it possible that research will help reduce demand for the natural psychoactive agent? While experts are confident that the use of 5-MeO-DMT from toads will remain, there is hope that synthetic research will lead to safer and more effective alternatives.
However, most initial studies on the therapeutic potential of 5-MeO-DMT are based on small samples or studies with limited observations, which adds to the uncertainty. Early results create optimism that the fast-acting psychoactive substance may become an accessible and affordable treatment. Doctors believe that a shorter duration of action may be preferable for patients, as these experiences can be challenging and anxiety-inducing.
Also, studies are underway to explore the potential benefits of synthetic 5-MeO-DMT for the treatment of anorexia and trauma in veterans and lifeguards starting in early 2024. If clinical trials confirm the therapeutic effects of the synthetic drug, it would make a strong argument for its use.