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5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), also known as O-methylbufotenin or mebufotenin (INNTooltip International Nonproprietary Name), is a naturally occurringpsychedelic of the tryptamine family.[6][1][5][2] It is found in a wide variety of plant species, and is also secreted by the glands of at least one toad species, the Colorado River toad.[6] It may occur naturally in humans as well.[6] Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America.[6][8] Slang terms include five-methoxy, the power, bufo, and toad venom.[9] The drug has been described as the most powerful psychedelic[10][11] and, by journalist Michael Pollan, as the "Mount Everest of psychedelics".[11][12]
5-MeO-DMT was first described by 1936, was first isolated from natural sources by 1959, and was first reported to be hallucinogenic by 1970.[11][6] The use of 5-MeO-DMT-containing toad venom was first described in 1984.[11][14] It is a controlled substance in some countries, for instance the United States, United Kingdom, Australia, and New Zealand.[6] The drug is used recreationally and several deaths have been reported in association with its use.[6][15] Use of 5-MeO-DMT is rare compared with other psychedelics, with only 0.003% of the United States general population having reported taking it in 2019 (compared to 8.5% for psilocybin).[12][16] 5-MeO-DMT is being developed for potential use in medicine in the treatment of neuropsychiatric disorders such as depression.[17][6][1][5]
The Church of the Tree of Life, founded in California in 1971 by John Mann but now defunct, declared the use of 5-MeO-DMT to be a sacrament. From approximately 1971 to the late 1980s, 5-MeO-DMT was discreetly available to its members.[20][21] Between 1970 and 1990, smoking of 5-MeO-DMT on parsley was probably one of the two most common forms of ingestion in the United States.[21][unreliable source?]
When smoked, the duration of the effects of 5-MeO-DMT can be as little as ten minutes; when insufflated, up to two hours, although the peak effects are usually in the range of 10–40 minutes.[22] Effects vary and can range from radical perspective shifting and perception of new insights, euphoria, immersive experiences, dissociation and non-responsiveness, sensual/erotic enhancement, to dysphoria, fear, terror, panic, and ego death.[23][better source needed]
The subjective effects of 5-MeO-DMT are described as distinct from those of DMT and other psychedelics.[5][6][12] Whereas DMT is described as producing more "information-rich" experiences, with "rich sensory phenomenology", visuals, and experiences of encountering entities and visiting other worlds, 5-MeO-DMT is described as having a relative lack of visual effects, producing a sense of "nothingness", and causing experiences that are said to be "content-free" and sometimes known as "whiteouts".[5][6][12] These experiences have been described as "beyond ordinary human comprehension", with a subjective impression of a void or amnesia of the experience.[5][6][12] In spite of this however, some have described the experiences as orgasmic, ecstatic, and blissful, whereas others have described them as terror or "information overwhelm".[5][12] As with DMT and other psychedelics, the experiences with 5-MeO-DMT are often described as overwhelming, profound, spiritual, religious, and/or mystical.[5][6][12]
The experiences of 5-MeO-DMT have been related to the experience of ecstatic seizures.[5]
Similarly to other serotonergic psychedelics, 5-MeO-DMT is a non-selectiveserotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C receptors, among others.[1][5][29][28] It is 4- to 10-fold more potent as a hallucinogen than DMT in humans.[2] In contrast to most serotonergic psychedelics however, it has been said that it is unclear that the hallucinogenic effects of 5-MeO-DMT are principally mediated by activation of the serotonin5-HT2A receptor.[5] In any case, 5-MeO-DMT does still activate the serotonin 5-HT2A receptor and does still produce psychedelic effects.[5] It has been proposed that 5-MeO-DMT be considered an "atypical" psychedelic.[5] This relates to the fact that 5-MeO-DMT has 100- to 1,000-fold selectivity for the serotonin 5-HT1A receptor over the serotonin 5-HT2A receptor and that the actions of 5-MeO-DMT appear to be primarily mediated by serotonin 5-HT1A receptor activation.[1][5][2][13] For example, the potencies of drugs substituting for 5-MeO-DMT in drug discrimination assays is well-correlated with their serotonin 5-HT1A receptor affinities, and the discriminative stimulus effects of 5-MeO-DMT are attenuated by serotonin 5-HT1A receptor antagonists.[2] However, there is partial generalization of 5-MeO-DMT to the selective serotonin 5-HT2 receptor agonist (–)-DOM in animals.[2] In accordance with the preceding findings, 5-MeO-DMT is reported to produce notably distinct subjective effects compared to DMT and other psychedelics in humans.[5]
Although 5-MeO-DMT shows dramatically higher affinity for the serotonin 5-HT1A receptor than for the serotonin 5-HT2A receptor, the situation appears to be very different in terms of its actual activational potencies at these receptors.[38][28][25] Its EC50Tooltip half-maximal effective concentration values have been found to be 1.80 to 3.87nM at the serotonin 5-HT2A receptor and 3.92 to 1,060nM at the serotonin 5-HT1A receptor.[38][28][25][34] For comparison, the EC50 values of DMT were found to be 38.3nM at the serotonin 5-HT2A receptor and >10,000nM at the serotonin 5-HT1A receptor in one of the same studies.[38][28] Hence, 5-MeO-DMT appears to be similarly potent or as much as 200-fold more potent as an agonist of the serotonin 5-HT2A receptor than of the serotonin 5-HT1A receptor.[38][28][25] In addition, 5-MeO-DMT is 10-fold more potent than DMT as an agonist of the serotonin 5-HT2A receptor.[38][28]
Bufotenin is an active metabolite of 5-MeO-DMT, formed by O-demethylation by cytochrome P450CYP2D6.[2] Bufotenin notably has much higher affinity for the serotonin 5-HT2A receptor than 5-MeO-DMT itself.[2] However, bufotenin does not seem to be extensively produced from 5-MeO-DMT in the brain.[2] In addition, peripherally formed bufotenin is less able to exert central effects due to its relative peripheral selectivity in terms of crossing into the brain.[2] Hence, the involvement of bufotenin in the psychoactive effects of 5-MeO-DMT is uncertain.[2]
The metabolism of 5-MeO-DMT can be dramatically reduced and its levels markedly augmented and prolonged by monoamine oxidase inhibitors (MAOIs).[2] In addition, MAOIs allow 5-MeO-DMT to become orally active in humans.[2] Combining 5-MeO-DMT with MAOIs has sometimes resulted in serotonin syndrome and death in humans.[2]
The Colorado River toad is a noted animal source of 5-MeO-DMT, first described in Bufo Alvarius: the Psychedelic Toad of the Sonoran Desert in 1984 by Ken Nelson (writing under the pseudonym of Albert Most). Smoking the parotoid secretions of the animal produces a powerful and short-lived psychedelic experience.[54] The smoking of I. alvarius secretions should not be confused with the urban legend of toad licking.[3] Since 1983, the animal has since became a popular source of 5-MeO-DMT for recreational or spiritual purposes.[55] Unfortunately, this increased demand and use of the toads as a source of 5-MeO-DMT has put strain on their populations.[56] Concerned with the ecological impacts of the growing use of I. alvarius secretions as a source of 5-MeO-DMT, Ken Nelson would later advocate for the use of synthetic 5-MeO-DMT and conservation of the Colorado River Toad.[57]
5-MeO-DMT is legal for personal use and possession in Canada,[75] though sale, distribution, and other activities involving the substance are illegal under Canadian federal law.
The Swedish government classified 5-MeO-DMT, listed as 5-metoxi-N,N-dimetyltryptamin (5-MeO-DMT) in their regulation SFS 2004:696, as "health hazard" under the Act on the Prohibition of Certain Goods Dangerous to Health [sv] in October 2004, making it illegal to sell or possess.[77]
5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients with treatment-resistant depression (TRD).[81]Biopharmaceutical company GH Research has sponsored a completed phase 1 study in healthy volunteers[82] and phase 1/2 study in TRD patients where 87.5% of patients with TRD were brought into remission on day 7 in the phase 2 part of the study.[83][84] GH Research is currently planning a phase 2b study in TRD patients and have received approval for studies in patients with bipolar II disorder and a current depressive episode and patients with postpartum depression.[85]
Beckley Psytech in collaboration with King's College London is evaluating the safety and tolerability of intranasal 5-MeO-DMT in healthy subjects, in a phase 1 study.[87][88] Beckley Psytech CEO Cosmo Feilding-Mellen sees a potential in the short-acting nature of 5-MeO-DMT compared to psilocybin: "Requiring one or two therapists to sit in a room with a single patient for the entire duration of an MDMA or psilocybin experience, which is essentially a whole working day, is probably going to be very resource-intensive and expensive. There is already a global shortage of psychotherapists, and this poses a potential bottleneck to patient access in the future."[89]
Ultra-short-acting psychedelics like DMT and 5-MeO-DMT may be advantageous compared to longer-acting psychedelics like psilocybin in terms of practicality for use as therapeutic interventions in clinical settings.[90][91]
Concerns have been raised about the potential use of 5-MeO-DMT in medicine due to the extreme and frequently challenging natures of the experiences.[12]
^ abBistue Millón MB, Noguera L, Bruno D, Vita L, Zanino M, Kassuha DE, et al. (July 2025). "Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study". Neuropsychopharmacology. doi:10.1038/s41386-025-02167-3. PMID40659913.
^Linden J, Robin D (2023). "Other psychedelics". Psychedelics as Psychiatric Medications. Oxford University PressOxford. p. 95–C8P41. doi:10.1093/med/9780192863607.003.0008. ISBN978-0-19-286360-7. We complete this chapter by paying some attention to what many feel is the most interesting and most powerful psychedelic of them all. It gives us great pleasure to introduce 5-methoxy-N, N-DMT (5-MeO), aka the 'God Molecule'. 5-MeO is an extremely powerful, naturally occurring, psychedelic tryptamine [...]
^ abcdefghDelgrasso A (17 February 2024). "Defining 5-MeO-DMT in Historical and Cultural Contexts". World Futures. 80 (2): 174–197. doi:10.1080/02604027.2024.2330255. ISSN0260-4027. Another influential psychedelic scholar, Grof (2006), considered 5-MeODMT the most potent entheogen [...] Pollan (2018), whose recent work has focused on how this compound creates a transcendent experience unlike any other psychedelic, called 5-MeO-DMT the "Mount Everest of psychedelics" (p. 274). [...] There is a notable distinction between 5-MeO-DMT and DMT, both of which are found in plants and animals across the world. DMT is often referred to as the "spirit molecule" due to its powerful hallucinogenic effects, which can cause intense spiritual experiences (Strassman, 2001). [...] Both substances can give users intense spiritual experiences, but their effects and safety profiles differ. 5-MeO-DMT is much stronger than DMT, so it is essential to use caution when ingesting it.
^Mann J, Gottlieb A (2015) [First published 1970]. "back cover". The Book of Sacraments: Ritual Use of Magical Plants. Ronin Publishing. ISBN978-1-57951-210-1.
^ abde la Fuente Revenga M, Fernández-Sáez N, Herrera-Arozamena C, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, et al. (June 2015). "Novel N-Acetyl Bioisosteres of Melatonin: Melatonergic Receptor Pharmacology, Physicochemical Studies, and Phenotypic Assessment of Their Neurogenic Potential". J Med Chem. 58 (12): 4998–5014. doi:10.1021/acs.jmedchem.5b00245. PMID26023814.
^Krebs-Thomson K, Ruiz EM, Masten V, Buell M, Geyer MA (December 2006). "The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats". Psychopharmacology. 189 (3): 319–329. doi:10.1007/s00213-006-0566-1. PMID17013638. S2CID23396616.
^Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. PMID17223101.
^Morris H (2021-02-02). "Preface". Bufo alvarius: The Psychedelic Toad of the Sonoran Desert (2021 ed.). Archived from the original on 2021-02-02. Retrieved 2023-10-20.
^Pachter IJ, Zacharias DE, Ribeiro O (1959). "Indole Alkaloids of Acer saccharinum (the Silver Maple), Dictyoloma incanescens, Piptadenia colubrina, and Mimosa hostilis". The Journal of Organic Chemistry. 24 (9): 1285–1287. doi:10.1021/jo01091a032. ISSN0022-3263.
^Gessner PK, Page IH (1 July 1962). "Behavioral effects of 5-methoxy-N:N-dimethyltryptamine, other tryptamines, and LSD". American Journal of Physiology. Legacy Content. 203 (1): 167–172. doi:10.1152/ajplegacy.1962.203.1.167. ISSN0002-9513.
^Holmstedt B (August 1965). "Tryptamine derivatives in Epená, an intoxicating snuff used by some South American Indian tribes". Arch Int Pharmacodyn Ther. 156 (2): 285–305. PMID5868939.
^Alexander Shulgin (1970). "Chemistry and Structure-Activity Relationships of the Psychotomimetics". In D. H. Efron (ed.). Psychotomimetic Drugs(PDF). New York: Raven Press. pp. 21–41.
^Gessner, P. K. (1970). Pharmacological Studies of 5-Methoxy-N,N-dimethyltryptamine, LSD and Other Hallucinogens. Psychotomimetic Drugs, 105–118. https://www.samorini.it/doc1/alt_aut/ek/gessner-pharmacological-studies-of-5-methoxy-dimethyltryptamine-lsd.pdf#page=2 "DR. SHULGIN: We have [5-MeO-DMT] in clinical trial now. It is much more active than dimethyltryptamine. It is much less active than LSD and it is only active parenterally, as is the case with DMT. This is about all I can say. DR. SNYDER: How does it compare with psilocin? DR. SHULGIN: It is more active than psilocin, but I can't say how much more with any confidence. DR. GESSNER: This is all in accord with our data. DR. SHULGIN: We used 5 to 10 mg of 5-methoxy-N,N-dimethyltryptamine; perhaps even a lower dose can be used."
^de Smet PA (December 1983). "A multidisciplinary overview of intoxicating enema rituals in the western hemisphere". J Ethnopharmacol. 9 (2–3): 129–166. doi:10.1016/0378-8741(83)90031-4. PMID6677814. Human experiments with 5-MeO-DMT seem to have been conducted only by Shulgin (1970), who briefly reported that a parenteral dose of 5—10 mg is active and revealed the following details in a letter to the author: "My clinical studies involved a total of 9 subjects, 4 males and 5 females, within the age range of 33 to 65 years. All were healthy volunteers, all with con- siderable experience with drugs that can alter one's state of consciousness. The parenteral route of administration was in all cases by inhalation of the fused free base suspended on Tanacetum vulgare in cigarette form. The onset of action occurs in less than 60 seconds, reaches a plateau in the 2nd to 3rd minute, and is largely dissipated at 20 minutes, although there may be some lingering awareness for the remainder of an hour. Centrally, there is the loss of some reality sense, some eyes-closed imagery and a general feeling of being enclosed and isolated in a sensory sense. Peripherally, there have been occasional tremors noted, and occasional mydriasis. These effects are from 6 to 10 mg of the free base. I have personally conducted no oral experiments and do not know its effects via this route".
^"关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
