In his bookTiHKAL (Tryptamines I Have Known and Loved),Alexander Shulgin lists 5-MeO-DMT's dose as 6 to 20mg smoked or 2 to 3mg by intravenous injection and itsduration as 1 to 2hours.[3] Other sources state the dose of 5-MeO-DMT to be 2 to 15mg smoked and its duration as 5 to 20minutes or 12minutes typically.[10] It has been described as having a steepdose–response curve.[15] 5-MeO-DMT is not orally active at doses of up to at least 35mg and is almost always used via smoking.[3] Theonset of 5-MeO-DMT smoked is 8seconds to 1minute, with peak effects occurring after 2 to 3minutes, although some report an onset or build-up of as long as 10 to 15minutes.[3] The main effects when smoked last about 10minutes, with a total duration of 20 to 60minutes.[3] Taken by intravenous injection, the onset of 5-MeO-DMT is within 1minute and the duration was 10minutes in one instance.[3] With harmaline doses of 70 to 150mg orally, 5-MeO-DMT becomes orally active at doses of 10 to 25mg, the onset is 15 to 18minutes, peak effects occur after 1.5hours, and the duration is at least 3 or 4hours.[3][7] In addition, harmaline at sufficient doses such as 150mg or more can add its own hallucinogenic effects to the experience.[7]
The effects of 5-MeO-DMT have been reported by Shulgin.[3] Theperceptual effects included no noticeablevisual effects orsensory involvement, not seeing anything whilst eyes shut except a bright white light, inability to see in general, multi-colorphosphene visuals filling entire visual field, a certainresonance ofauditory perception or electrical buzzing that synchronized with visual perception, slightly diminished hearing,ear ringing, feeling barraged bystimuli,rush, and a tremendous and intense sense of speed and acceleration.[3] Other effects included a "white-out" or "singularity" experience (as opposed to a "black-out"), mental activity almost absent, mind completely referenceless, cosmic consciousness type of experience, feelings of and longing for connection and transcendence, feeling like one is experiencing all possible thoughts and realities simultaneously, feeling like one is experiencing a very large number of objects, situations, andemotions all at once instead of only one at a time,feeling like one is an ocean, intensedepersonalization, impressiverecall of earlymemories and emotional significance of these memories,time constriction (such as experiencing 40minutes as mere seconds), andinsights.[3]
Effects related tospatial and bodily awareness included altered body perception, normal physical perceptions dissolving away from awareness, loss of contact with one's body and surroundings, feeling like one was not there in one's body or in time, feeling like all the blood in one's body had turned to concrete, and not being able to tell if eyes were closed or open.[3]Emotional effects included a sense ofexcitement, feelings ofawe andwonder, feelingamazed or "blown away", feelings oflove andenergy, feelings ofecstasy, emotions synchronized with visuals, strong feelings of gratitude for the experience, feeling overwhelmed, feeling "scared the hell out", feeling the "energy of terror", screaming in one's head,fear of death, feeling like one had died or killed themselves, feeling at risk ofpsychic damage, and relief upon coming down.[3] Further effects included an intensity greater than anything one has experienced before, simply the most intense experience possible, feeling like the entire universe had exploded through one's consciousness, feeling like there is no possibility of examining the experience, an inability to judge by any method of the mind, feeling conked on the head,little or no memory of the experience, and loss of continuity of consciousness like ablack-out from too muchalcohol.[3]
5-MeO-DMT was described by Shulgin as being remarkablypotent, more potent than DMT, and as having a slightly faster onset than DMT when smoked.[3] More specifically, it is 4- to 20-fold more potent than DMT.[2][15][3] The drug is said to be a very strong and quite intensehallucinogen.[3] There is an ability to break through to a similar space as DMT, but it is said to be "more like receiving grace" and to be much more relaxed than DMT and less terrifying.[3] One report commented that 5-MeO-DMT was like adding theMDMA (ecstasy) experience to DMT.[3] 5-MeO-DMT was one of the only psychedelics inTiHKAL that resulted in a plus-four experience on theShulgin Rating Scale.[3] Another psychedelic tryptamine that produced similar effects to 5-MeO-DMT was5-MeO-MiPT at sufficiently high doses smoked.[3] 5-MeO-DMT seems to be like a cross between DMT and5-MeO-pyr-T in terms of its effects.[3] The latter shares many commonalities with 5-MeO-DMT, but has few or no psychedelic effects and has pronounced negative effects.[3] Other5-methoxytryptamines like5-MeO-DET and5-MeO-DPT were plagued by dose-limiting side effects that resulted in Shulgin having an unfavorable impression of them, whereas5-MeO-DiPT and5-MeO-DALT produced only light psychedelic effects.[3]
In other published sources besidesTiHKAL, the subjective effects of 5-MeO-DMT are described as distinct from those of DMT and other psychedelics.[5][8][15] Whereas DMT is described as producing more "information-rich" experiences, with "rich sensory phenomenology", visuals, and experiences ofencountering 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][8][15] These experiences have been described as "beyond ordinary human comprehension", with a subjective impression of a void or amnesia of the experience.[5][8][15] In spite of this however, some have described the experiences asorgasmic, ecstatic, andblissful, whereas others have described them as terror or "information overwhelm".[5][15] As with DMT and other psychedelics, the experiences with 5-MeO-DMT are often described as overwhelming, profound,spiritual,religious, and/ormystical.[5][8][15] The experiences of 5-MeO-DMT have also been related to the experience ofecstatic seizures.[5] 5-MeO-DMT has been described as the most powerful psychedelic[13][14] and byMichael Pollan as the "Mount Everest of psychedelics".[14][15]
Thephenomenology of 5-MeO-DMT given intransally has been formallyclinically studied in aphase 1clinical trial more recently.[6] It is described as having a rapid onset of 8 to 15minutes, a short duration of 45 to 60minutes, distinctive subjective effects from other psychedelics, a relative lack of visual effects, strong emotional and bodily experiences, emotional breakthroughs, and personal insights, among other effects.[6]
Similarly to other serotonergic psychedelics, 5-MeO-DMT is anon-selectiveserotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A,5-HT2B, and5-HT2C receptors, among others.[1][5][30][29][36] It is 4- to 10-fold morepotent 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 theserotonin5-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-foldselectivity for the serotonin5-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][16] For example, thepotencies of drugs substituting for 5-MeO-DMT indrug discrimination assays is well-correlated with their serotonin 5-HT1A receptoraffinities, and thediscriminative stimulus effects of 5-MeO-DMT are attenuated by serotonin 5-HT1A receptorantagonists.[2] However, there is partialgeneralization of 5-MeO-DMT to the selective serotonin5-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.[40][29][26] ItsEC50Tooltip 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.[40][29][26][35] For comparison, theEC50 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.[40][29] 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.[40][29][26] In addition, 5-MeO-DMT is 10-fold more potent than DMT as an agonist of the serotonin 5-HT2A receptor.[40][29]
Bufotenin is anactive metabolite of 5-MeO-DMT, formed byO-demethylation bycytochrome P450CYP2D6.[2] Bufotenin notably has much higheraffinity 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]
Themetabolism of 5-MeO-DMT can be dramatically reduced and its levels markedly augmented and prolonged bymonoamine oxidase inhibitors (MAOIs).[2] In addition, MAOIs allow 5-MeO-DMT to becomeorally active in humans.[2] Combining 5-MeO-DMT with MAOIs has sometimes resulted inserotonin syndrome and death in humans.[2]
TheColorado River toad is a noted animal source of 5-MeO-DMT, first described inBufo Alvarius: the Psychedelic Toad of the Sonoran Desert in 1984 by Ken Nelson (writing under the pseudonym of Albert Most). Smoking theparotoid secretions of the animal produces a powerful and short-livedpsychedelic experience.[22] The smoking ofI. alvarius secretions should not be confused with the urban legend oftoad licking.[3] Since 1983, the animal has become a popular source of 5-MeO-DMT for recreational orspiritual purposes.[56] Unfortunately, this increased demand and use of the toads as a source of 5-MeO-DMT has put strain on their populations.[57] Concerned with the ecological impacts of the growing use ofI. 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.[58]
5-MeO-DMT is the common informal name of the drug and an acronym of one of its chemical names.Mebufotenin is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name. Other names can includeO-methylbufotenin,O-methyl-5-HO-DMT, andO,N,N-trimethylserotonin.
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 asacrament. From approximately 1971 to the late 1980s, 5-MeO-DMT was discreetly available to its members.[75][76] Between 1970 and 1990, smoking of 5-MeO-DMT onparsley was probably one of the two most common forms ofingestion in theUnited States.[76][unreliable source?]
5-MeO-DMT is legal for personal use and possession in Canada,[78] 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 Lagen om förbud mot vissa hälsofarliga varor (Act on the Prohibition of Certain Goods Dangerous to Health) in October 2004, making it illegal to sell or possess.[80]
5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients withtreatment-resistant depression (TRD).[86]Biopharmaceutical company GH Research has sponsored a completed phase 1 study in healthy volunteers[87] 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.[88][89] 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.[90]
In February 2025, GH Research announced that their Phase 2b clinical trial of GH001, met its primary endpoint in patients with TRD.[91] The trial demonstrated a placebo-adjusted reduction of 15.5 points on theMontgomery-Åsberg Depression Rating Scale (MADRS) at day 8, with 57.7% of patients achievingremission compared to 0% in the placebo group.[91] The trial also met allsecondary endpoints, and the treatment was well-tolerated with noserious adverse events reported.[91]
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.[92][93] 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."[94]
Ultra-short-acting psychedelics likedimethyltryptamine (DMT) and 5-MeO-DMT may be advantageous compared to longer-acting psychedelics likepsilocybin in terms of practicality for use as therapeutic interventions in clinical settings.[95][96]
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.[15]
^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.50 (11):1715–1723.doi:10.1038/s41386-025-02167-3.PMC 12436647.PMID40659913.
^abLinden 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 [...]
^abcdefghijDelgrasso 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.
^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. Retrieved2023-10-20.
^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".
^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.
^"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 fromthe original on 1 October 2015. Retrieved1 October 2015.
