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Although many plants and animals produce 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), it is most famously found in the skin glands of a particular toxic desert toad (Incilius alvarius, formerly Bufo alvarius) along with its active, O-demethylated metabolite bufotenine.

First synthesized in 1936 (Hoshino 1936), 5-MeO-DMT shares a chemical structure with psilocybin and the traditional psychedelics DMT (N,N-dimethyltryptamine) due to its close structural resemblance to serotonin (5-hydroxytryptamine [5-HT]). Though many researchers have suggested that the 5 HT1A subtype has functional dominance, 5-MeO-DMT’s pharmacological activity may be different. It primarily acts as a selective serotonin receptor agonist at both 5-HT1A and 5-HT2A receptors (Spencer 1987, Winter 2000, Krebs-Thomson 2006, Shen 2010a).

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There have been several reports of 5-MeO-DMT use in studies of recreational, spiritual, and therapeutic uses as well as epidemiological studies (Weil 1994, Shulgin 1997, Barsuglia 2018, Davis 2018, Cox 2018a, Cox 2018b, Davis 2019, Uthaug 2019). Self-reported improvements in a range of mental health symptoms, such as anxiety, depression, substance use disorders, and PTSD, may be associated with 5-MeO-DMT use, according to evidence from these research (Davis 2018, Cox 2018a, Cox 2018b, Davis 2019, Uthaug 2019).

Due to cost savings and improved patient accessibility, 5-MeO-DMT, a potentially strong, fast-acting substance with a brief psychedelic effect in humans, may have important health care ramifications.

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A naturally occurring psychedelic belonging to the tryptamine family, 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is sometimes referred to as O-methylbufotenin or mebufotenin (INNTooltip International Nonproprietary Name). Numerous plant species contain it, and at least one toad species—the Colorado River toad—secretes it through its glands. Humans may also naturally experience it. It has been used as an entheogen in South America, just as its near relatives bufotenin (5-HO-DMT) and dimethyltryptamine (DMT). Five-methoxy, the power, bufo, and toad venom are examples of slang phrases.  Journalist Michael Pollan has referred to the drug as the “Mount Everest of psychedelics” and said it is the most potent psychedelic.

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5-MeO-DMT side effects include nausea, vomiting, headaches, hypertension, exhaustion, anxiety, panic, terror, disorientation, paranoia, sobbing, loss of consciousness and motor control, and reactivations. Among other serotonin receptors, the medication functions as a non-selective agonist of 5-HT1A and 5-HT2A receptors. In contrast to the majority of other serotonergic psychedelics, 5-MeO-DMT has an affinity for the serotonin 5-HT1A receptor that is 100–1,000 times greater than that of the serotonin 5-HT2A receptor. 5-MeO-DMT has been characterized as a “atypical” psychedelic in this regard, producing subjective effects that are significantly different from those of DMT and other psychedelics, such as a relative lack of visual effects.

However, the majority of 5-MeO-DMT users consistently report having mystical experiences. 5-MeO-DMT, like DMT, is only effective when taken orally. It acts quickly and lasts for a brief period of time. In humans, 5-MeO-DMT is four to twenty times more powerful than DMT.

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5-MeO-DMT was initially identified as a hallucinogenic substance by 1970, after being obtained from natural sources by 1959 and characterized by 1936. In 1984, the application of toad venom containing 5-MeO-DMT was initially reported. In certain nations, including the US, UK, Australia, and New Zealand, it is a controlled substance. The drug is used recreationally, and its use has been linked to multiple fatalities. In comparison to other psychedelics, 5-MeO-DMT use is uncommon; only 0.003% of Americans reported using it in 2019 (compared to 8.5% for psilocybin). 5-MeO-DMT is being researched for possible medical application in the management of neuropsychiatric conditions including depression.

Uses of 5-MeO-DMT
1. Recreational
5 MeO-DMT is a recreational drug.
2. Medical
Initial clinical results indicate that 5-MeO-DMT may have anxiolytic and antidepressant properties.

3. Religious
John Mann established the now-defunct Church of the Tree of Life in California in 1971, and it proclaimed 5-MeO-DMT to be a sacrament. Members may obtain 5-MeO-DMT covertly from around 1971 until the late 1980s. In the United States, smoking 5-MeO-DMT on parsley was likely one of the two most popular ways to consume the drug between 1970 and 1990.

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