Chemistry:5-MeO-DMT

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5-MeO-DMT, also known as 5-methoxy-N,N-dimethyltryptamine, as well as O-methylbufotenin or mebufotenin, is an atypical psychedelic drug, entheogen, and alkaloid of the tryptamine and 5-methoxytryptamine families.[1][2][3][4] It is found naturally in a wide variety of plant species, and is also secreted by the glands of at least one toad species, the Colorado River toad (Incilius alvarius, formerly Bufo alvarius).[1] It may occur naturally in humans as well.[1] Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America.[1][5] Slang terms include five-methoxy, the power, bufo, and toad venom.[6] The drug has been described as the most powerful psychedelic[7][8] and, by journalist Michael Pollan, as the "Mount Everest of psychedelics".[8][9]

Adverse effects of 5-MeO-DMT include sickness, vomiting, headache, chest pressure, fatigue, anxiety, fear, terror, confusion, paranoia, crying, loss of awareness and motor control, and reactivations.[9] The drug acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT1A and 5-HT2A receptors, among others.[2][3][10] However, 5-MeO-DMT differs from most other serotonergic psychedelics in having much greater activity at the serotonin 5-HT1A receptor in addition to the serotonin 5-HT2A receptor.[11][2][3][10] In relation to this, 5-MeO-DMT has been described as an "atypical" psychedelic and as producing subjective effects notably distinct from those of DMT and other psychedelics, for instance having a relative lack of visual effects.[1][2][3][12] Nonetheless, 5-MeO-DMT reliably produces mystical experiences in most people who take it.[9] Like DMT, 5-MeO-DMT is only active non-orally and has a very rapid onset and short duration.[2][3][12] However, 5-MeO-DMT is 4- to 20-fold more potent than DMT in humans.[4][9][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.[8][1] The use of 5-MeO-DMT-containing toad venom was first described in 1984.[8][13] It is a controlled substance in some countries, for instance the United States, United Kingdom, Australia, and New Zealand.[1] The drug is used recreationally and several deaths have been reported in association with its use.[1][14] 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).[9][15] 5-MeO-DMT is being developed for potential use in medicine in the treatment of neuropsychiatric disorders such as depression.[16][1][2][3]

Use and effects

5-MeO-DMT is used as a recreational drug and as an entheogen.[2][1][12] It is not orally active, requiring a parenteral route such as smoking to produce effects.[2][1][12] Other non-oral routes such as intravenous injection, intramuscular injection, rectal administration, sublingual administration, or intranasal administration have also less commonly been used.[2][1][12] In addition to non-oral administration, 5-MeO-DMT can be combined with a monoamine oxidase inhibitor (MAOI) such as the reversible inhibitor of monoamine oxidase A (RIMA) harmaline to allow for oral activity and a much longer duration than it would have otherwise.[17] However, combination of 5-MeO-DMT with MAOIs can also result in accidental overdose, including instances of serotonin syndrome and death.[4] In addition to pure synthetic 5-MeO-DMT, it is often used by smoking in the form of the venom taken from the Colorado River toad (Incilius alvarius, formerly Bufo alvarius and also known as the Sonoran Desert toad).[1][13][18][19][20]

In his book TiHKAL (Tryptamines I Have Known and Loved), Alexander Shulgin lists 5-MeO-DMT's dose as 6 to 20 mg smoked or 2 to 3 mg by intravenous injection and its duration as 1 to 2 hours.[12] Other sources state the dose of 5-MeO-DMT to be 2 to 15 mg smoked and its duration as 5 to 20 minutes or 12 minutes typically.[21] It has been described as having a steep dose–response curve.[9] 5-MeO-DMT is not orally active at doses of up to at least 35 mg and is almost always used via smoking.[12] The onset of 5-MeO-DMT smoked is 8 seconds to 1 minute, with peak effects occurring after 2 to 3 minutes, although some report an onset or build-up of as long as 10 to 15 minutes.[12] The main effects when smoked last about 10 minutes, with a total duration of 20 to 60 minutes.[12] Taken by intravenous injection, the onset of 5-MeO-DMT is within 1 minute and the duration was 10 minutes in one instance.[12] With harmaline doses of 70 to 150 mg orally, 5-MeO-DMT becomes orally active at doses of 10 to 25 mg, the onset is 15 to 18 minutes, peak effects occur after 1.5 hours, and the duration is at least 3 or 4 hours.[12][17] In addition, harmaline at sufficient doses such as 150 mg or more can add its own hallucinogenic effects to the experience.[17]

The effects of 5-MeO-DMT have been reported by Shulgin.[12] The perceptual effects included no noticeable visual effects or sensory involvement, not seeing anything whilst eyes shut except a bright white light, inability to see in general, multi-color phosphene visuals filling entire visual field, a certain resonance of auditory perception or electrical buzzing that synchronized with visual perception, slightly diminished hearing, ear ringing, feeling barraged by stimuli, rush, and a tremendous and intense sense of speed and acceleration.[12] 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, and emotions all at once instead of only one at a time, feeling like one is an ocean, intense depersonalization, impressive recall of early memories and emotional significance of these memories, time constriction (such as experiencing 40 minutes as mere seconds), and insights.[12]

Effects related to spatial 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.[12] Emotional effects included a sense of excitement, feelings of awe and wonder, feeling amazed or "blown away", feelings of love and energy, feelings of ecstasy, 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 of psychic damage, and relief upon coming down.[12] 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 a black-out from too much alcohol.[12]

Behavioral effects included falling over while sitting, curling up in a fetal position, squirming and writhing around, making frightening noises, and alarming other people.[12] Physical side effects included physical weakness, shakiness, tremors, shivers emanating from the head, center, or heart, and slight nausea.[12] The taste when smoking was described as mild, with none of the plastic taste of dimethyltryptamine (DMT).[12] In the case of an unspecified large overdose smoked, the person lapsed into a coma-like state, their face turned purple, they stopped breathing and had to be resuscitated multiple times, and they experienced a several-day psychosis necessitating antipsychotics.[12]

5-MeO-DMT was described by Shulgin as being remarkably potent, more potent than DMT, and as having a slightly faster onset than DMT when smoked.[12] More specifically, it is 4- to 20-fold more potent than DMT.[4][9][12] The drug is said to be a very strong and quite intense hallucinogen.[12] 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.[12] One report commented that 5-MeO-DMT was like adding the MDMA (ecstasy) experience to DMT.[12] 5-MeO-DMT was one of the only psychedelics in TiHKAL that resulted in a plus-four experience on the Shulgin Rating Scale.[12] Another psychedelic tryptamine that produced similar effects to 5-MeO-DMT was 5-MeO-MiPT at sufficiently high doses smoked.[12] 5-MeO-DMT seems to be like a cross between DMT and 5-MeO-pyr-T in terms of its effects.[12] The latter shares many commonalities with 5-MeO-DMT, but has few or no psychedelic effects and has pronounced negative effects.[12] Other 5-methoxytryptamines like 5-MeO-DET and 5-MeO-DPT were plagued by dose-limiting side effects that resulted in Shulgin having an unfavorable impression of them, whereas 5-MeO-DiPT and 5-MeO-DALT produced only light psychedelic effects.[12]

In other published sources besides TiHKAL, the subjective effects of 5-MeO-DMT are described as distinct from those of DMT and other psychedelics.[3][1][9] 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".[3][1][9] These experiences have been described as "beyond ordinary human comprehension", with a subjective impression of a void or amnesia of the experience.[3][1][9] 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".[3][9] As with DMT and other psychedelics, the experiences with 5-MeO-DMT are often described as overwhelming, profound, spiritual, religious, and/or mystical.[3][1][9] The experiences of 5-MeO-DMT have also been related to the experience of ecstatic seizures.[3] 5-MeO-DMT has been described as the most powerful psychedelic[7][8] and by Michael Pollan as the "Mount Everest of psychedelics".[8][9]

The phenomenology of 5-MeO-DMT given intransally has been formally clinically studied in a phase 1 clinical trial more recently.[22] It is described as having a rapid onset of 8 to 15 minutes, a short duration of 45 to 60 minutes, 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.[22]

Contraindications

Adverse effects

5-MeO-DMT has various possible adverse effects.[1][2][12]

Overdose

There have been cases of death with 5-MeO-DMT.[1][23][24] The estimated lethal dose of 5-MeO-DMT relative to a typical recreational dose in humans is unknown.[23] The median lethal dose (LD50) in animals varies widely, ranging from 1 to 5 mg/kg i.v. in sheep to 48 mg/kg i.v. in mice.[23] In one case, combination of 5-MeO-DMT with harmala alkaloids, which act as monoamine oxidase inhibitors (MAOIs), as well as with other drugs, resulted in death.[23] However, the exact contribution of 5-MeO-DMT in this case is difficult to determine.[23]

Interactions

5-MeO-DMT can be strongly potentiated by combination with monoamine oxidase inhibitors (MAOIs).[2][1][4][12] In addition, it can become orally active with an extended duration in combination with MAOIs.[4][12] These interactions have the potential to result in serious toxicity and death.[2][1][4][24]

Pharmacology

Pharmacodynamics

Activities of 5-MeO-DMT
Target Affinity (Ki, nM)
5-HT1A 1.9–28 (Ki)
3.4–1,060 (EC50)
68–98% (Emax)
5-HT1B 14–351 (Ki)
1.53 (EC50)
78% (Emax)
5-HT1D 2.3–20 (Ki)
37 (EC50)
98% (Emax)
5-HT1E 360–528 (Ki)
92–160 (EC50)
119% (Emax)
5-HT1F 37 (Ki)
14 (EC50)
93% (Emax)
5-HT2A 15–2,011 (Ki)
1.76–784 (EC50)
82–106% (Emax)
5-HT2B 19–3,884 (Ki)
5.9–30 (EC50)
21–73% (Emax)
5-HT2C 42–538 (Ki)
7.1–31 (EC50)
84–94% (Emax)
5-HT3 >10,000
5-HT4 >10,000 (EC50)
5-HT5A 277–505 (Ki)
110 (EC50)
107% (Emax)
5-HT6 6.5–78 (Ki)
0.24 (EC50)
125% (Emax)
5-HT7 3.9–30 (Ki)
65.7 (EC50)
107% (Emax)
MT1 210 (Ki)
257 (EC50)
MT2 16 (Ki)
112 (EC50)
α1A 4,373–>10,000
α1B 2,188–>10,000
α1D ND
α2A 574–1,890
α2B 430–>10,000
α2C 206–2,174
β1 >10,000
β2 2,679–>10,000
β3 >10,000
D1 80–>10,000
D2 3,562–>10,000
D3 498–>10,000
D4 1,422–>10,000
D5 >10,000
H1 7,580–>10,000
H2–H4 >10,000
M1–M5 >10,000
σ1 >10,000
σ2 >10,000
KOR >10,000
SERT 2,032–>10,000 (Ki)
2,184–>10,000 (IC50)
10,000 (EC50)
NET 2,859–>10,000 (Ki)
10,000 (IC50)
10,000 (EC50)
DAT >10,000 (Ki)
10,000 (IC50)
10,000 (EC50)
Notes: The smaller the value, the more avidly the drug binds to the site. Proteins are mostly but not exclusively human. Refs:[1][10][25][26][27][28][29][30][31][32][33][34][35][36]

5-MeO-DMT is a methoxylated derivative of dimethyltryptamine (DMT). While most common psychedelics are believed to primarily elicit psychological effects through agonism of serotonin 5-HT2A receptors, 5-MeO-DMT shows 1,000-fold greater affinity for the serotonin 5-HT1A receptor over the serotonin 5-HT2A receptor.[25] In line with its affinity for serotonin 5-HT1A receptors, 5-MeO-DMT is extremely potent at suppressing the firing of dorsal raphe nucleus serotonin neurons.[37] Further, its activity in rats was attenuated with the selective serotonin 5-HT1A receptor antagonist WAY-100635, while selective serotonin 5-HT2A receptor antagonist volinanserin failed to demonstrate any change.[38] Additional mechanisms of action such as inhibition of monoamine reuptake may also be involved in its effects.[39]

Similarly to other serotonergic psychedelics, 5-MeO-DMT is a non-selective serotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C receptors, among others.[2][3][30][29][36] It shows pronounced biased agonism at the serotonin 5-HT2C receptor.[40] The drug is 4- to 10-fold more potent as a hallucinogen than DMT in humans.[4] 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 serotonin 5-HT2A receptor.[3] In any case, 5-MeO-DMT does still activate the serotonin 5-HT2A receptor and does still produce psychedelic effects.[3] It has been proposed that 5-MeO-DMT be considered an "atypical" psychedelic.[3] 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.[2][3][4][10] 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 almost completely blocked (~80%) by serotonin 5-HT1A receptor antagonists like WAY-100,635.[4][41] However, there is partial generalization of 5-MeO-DMT to the selective serotonin 5-HT2 receptor agonist (–)-DOM in animals.[4] In addition, the selective serotonin 5-HT2A receptor antagonist volinanserin subtly reduces (~20%) the 5-MeO-DMT interoceptive cue, suggesting a minor contribution of this receptor.[41] Selective antagonists of other serotonin receptors, including the serotonin 5-HT1B, 5-HT2B, and 5-HT2C receptors, had no effect on the discriminative stimulus effects of 5-MeO-DMT.[41] In accordance with the preceding findings, which suggest effects mediated primarily by the serotonin 5-HT1A receptor and to a lesser extent by the serotonin 5-HT2A receptor, 5-MeO-DMT is reported to produce distinct subjective effects compared to DMT and other psychedelics in humans.[3]

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.[42][29][26] Its EC50 values have been found to be 1.80 to 3.87 nM at the serotonin 5-HT2A receptor and 3.92 to 1,060 nM at the serotonin 5-HT1A receptor.[42][29][26][35] For comparison, the EC50 values of DMT were found to be 38.3 nM at the serotonin 5-HT2A receptor and >10,000 nM at the serotonin 5-HT1A receptor in one of the same studies.[42][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.[42][29][26] In addition, 5-MeO-DMT is 10-fold more potent than DMT as an agonist of the serotonin 5-HT2A receptor.[42][29]

Besides serotonin receptors, 5-MeO-DMT is an agonist of the melatonin MT1 and MT2 receptors.[28][35][34] Unlike DMT, 5-MeO-DMT is not a ligand or agonist of the sigma receptors.[1][35][34] In contrast to certain other tryptamines, 5-MeO-DMT is inactive as a monoamine releasing agent, including of serotonin, norepinephrine, and dopamine.[29] However, it is a weak serotonin reuptake inhibitor, with an IC50 value of 2,184 nM.[29] Conversely, it is inactive as a dopamine and norepinephrine reuptake inhibitor (IC50 = >10,000 nM).[29]

Similarly to DMT, but in contrast to most other psychedelics, like LSD and psilocybin,[43][44] there appears to be very little development of tolerance with 5-MeO-DMT.[1][29][2][3] In fact, there may even be sensitization to the effects of 5-MeO-DMT.[3] The lack of tolerance development with 5-MeO-DMT may be due to biased agonism of the serotonin 5-HT2A receptor.[1] More specifically, 5-MeO-DMT activates the Gq signaling pathway of the serotonin 5-HT2A receptor with much less potency in recruiting β-arrestin2.[1][29] Activation of β-arrestin2 is linked to receptor downregulation and tachyphylaxis.[44][45][46]

Pharmacokinetics

Absorption

5-MeO-DMT is not orally active and must be administered parenterally.[12]

Distribution

5-MeO-DMT is lipophilic and is thought to easily cross the blood–brain barrier.[4] Accordingly, 5-MeO-DMT readily accumulates in the brain in animals with levels higher than in blood.[4] This is in notable contrast to bufotenin (5-HO-DMT or N,N-dimethylserotonin) and serotonin (5-HT), which are hydrophilic and have varying degrees of peripheral selectivity.[4][47][48]

Metabolism

Bufotenin is an active metabolite of 5-MeO-DMT, formed by O-demethylation by cytochrome P450 CYP2D6.[4] Bufotenin notably has much higher affinity for the serotonin 5-HT2A receptor than 5-MeO-DMT itself.[4] However, bufotenin does not seem to be extensively produced from 5-MeO-DMT in the brain.[4] 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.[4] Hence, the involvement of bufotenin in the psychoactive effects of 5-MeO-DMT is uncertain.[4]

The metabolism of 5-MeO-DMT can be dramatically reduced and its levels markedly augmented and prolonged by monoamine oxidase inhibitors (MAOIs).[4] In addition, MAOIs allow 5-MeO-DMT to become orally active in humans.[4] Combining 5-MeO-DMT with MAOIs has sometimes resulted in serotonin syndrome and death in humans.[4]

Elimination

The elimination half-life of 5-MeO-DMT, administered sublingually, was found to be 28 minutes.[49]

Chemistry

5-MeO-DMT, also known as 5-methoxy-N,N-dimethyltryptamine, is a substituted tryptamine derivative.[12] It is the 5-methoxylated derivative of N,N-dimethyltryptamine (DMT), the N,N-dimethylated derivative of 5-methoxytryptamine (5-MT; mexamine), and the O-methylated derivative of bufotenin (5-HO-DMT).[12]

Properties

5-MeO-DMT has a relatively high experimental log P of 3.30.[4][48]

Synthesis

The chemical synthesis of 5-MeO-DMT has been described.[50][12][51][52]

Analogues and derivatives

Analogues and derivatives of 5-MeO-DMT include dimethyltryptamine (DMT), 5-methoxytryptamine (5-MT or 5-MeO-T), 5-MeO-NMT, 5-MeO-MET, 5-MeO-DET, 5-MeO-MPT, 5-MeO-EPT, 5-MeO-DPT, 5-MeO-MiPT, 5-MeO-EiPT, 5-MeO-PiPT, 5-MeO-DiPT, 5-MeO-MALT, 5-MeO-DALT, 5-MeO-pyr-T, 5-EtO-DMT, 5-MeO-2-TMT (2-methyl-5-MeO-DMT), EMDT (2-ethyl-5-MeO-DMT), psilomethoxin (4-hydroxy-5-MeO-DMT; 5-methoxypsilocin), 5-MeO-AMT, α,N,N,O-TeMS (5-MeO-α,N,N-TMT), 4-MeO-DMT, 6-MeO-DMT, 7-MeO-DMT, and dimemebfe (5-MeO-BFE), among others.[12]

Some cyclized tryptamine and/or partial lysergamide derivatives of 5-MeO-DMT include N-DEAOP-5-MeO-NMT, 6-MeO-RU-28306, 6-methoxyharmalan, ibogaine, and 12-methoxy-LSD, among others.[12]

A deuterated isotopologue of 5-MeO-DMT is 5-MeO-DMT-d4 (α,α,β,β-tetradeutero-5-MeO-DMT).[53][27]

Natural occurrence

Plants

Plant sources of 5-MeO-DMT
Family Species
Rutaceae Dictyoloma incanescens,[54] Limonia acidissima,[55] Melicope leptococca[56]
Fabaceae Anadenanthera peregrina,[57] Acacia auriculiformis,[57] Acacia victoriae,[57] Desmodium gangeticum,[57] Lespedeza bicolor,[56][55] Mimosa pudica,[57] Mucuna pruriens,[55][56] Phyllodium pulchellum[55][56]
Poaceae Phalaris tuberosa[57]
Malpighiaceae Diplopterys cabrerana[58]
Cactaceae Echinocereus salm-dyckianus,[55] Echinocereus triglochidiatus[55]
Myristicaceae Horsfieldia superba,[55] Iryanthera macrophylla,[55] Osteophloeum platyspermum,[58] Virola theiodora,[55] V. calophylla,[58] V. multinervia,[58] V. peruviana,[58] V. rufula,[58] V. venosa[58]

There are various known plant sources of 5-MeO-DMT.[57]

Toads

Incilius alvarius (formerly Bufo alvarius), also known as the Colorado River toad or as the Sonoran Desert toad, produces 5-MeO-DMT in its venom.

Incilius alvarius, formerly known as Bufo alvarius and also known as the Colorado River toad or as the Sonoran Desert 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).[59][60][56] Smoking the parotoid secretions of the animal produces a powerful and short-lived psychedelic experience.[18] The smoking of I. alvarius secretions should not be confused with the urban legend of toad licking.[12] Since 1983, the animal has become a popular source of 5-MeO-DMT for recreational or spiritual purposes.[61] Unfortunately, this increased demand and use of the toads as a source of 5-MeO-DMT has put strain on their populations.[62] 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.[63]

Fungi

Fungal sources of 5-MeO-DMT include Amanita citrina[58] and Amanita porphyria.[58]

History

5-MeO-DMT was first synthesized by Toshio Hoshino in 1935.[8][1][64] It was isolated from the flowering plant Dictyoloma incanescens in 1959.[1][65] The drug was subsequently isolated from numerous other plant, fungal, and animal sources over time.[8][1] The behavioral effects of 5-MeO-DMT in animals were first reported by 1961.[66][67][68][69][70] In 1965, 5-MeO-DMT was reported to be the main component of the hallucinogenic snuff known variously as parica, epena, or yakee that is prepared and used from the resin of the Virola theiodora tree by indigenous people in Northern South America.[66][71][67][72] It was isolated from the toad Incilius alvarius (formerly Bufo alvarius and also known as the Sonoran Desert toad, Colorado River toad, or simply bufo) by Vittorio Erspamer by 1965.[8][1][73][74]

Alexander Shulgin briefly reported that 5-MeO-DMT was hallucinogenic in humans, via parenteral but not oral routes, in 1970, with additional details published later on.[66][71][75][76][77][12] Albert Most, real name Ken Nelson, was the first to describe the use of Incilius alvarius toad venom as a psychedelic in his published pamphlet Bufo Alvarius: the Psychedelic Toad of the Sonoran Desert in 1984.[8] Subsequently, Andrew Weil and Wade Davis, in part citing the pamphlet, described the psychoactive effects of the toad in the scientific literature in 1992.[13][78] In addition, they described the finding as the first instance of a psychedelic from an animal source to be discovered.[13] Recreational use of the toads, beyond the pamphlet, was encountered by the late 1980s and became a media sensation.[79] 5-MeO-DMT became a controlled substance in the United States in 2009.[1]

Society and culture

Names

5-MeO-DMT is the common informal name of the drug and an acronym of one of its chemical names. Mebufotenin is the generic name of the drug and its INN. Other names can include O-methylbufotenin, O-methyl-5-HO-DMT, and O,N,N-trimethylserotonin.

Religious use

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.[80][81] 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.[81]

Australia

As a structural analog of N,N-dimethyltryptamine (DMT), 5-MeO-DMT is a Schedule 9 prohibited substance under the Poisons Standard.[82]

Canada

5-MeO-DMT is not an explicitly nor implicitly controlled substance in Canada as of 2025.[83][84]

China

As of October 2015, 5-MeO-DMT is a controlled substance in China.[85]

Germany

As of 2001 5-MeO-DMT is listed as a controlled substance. Attachement I BtMG. BGBl. I 2001, 1180 - 1186;

Sweden

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.[86]

Turkey

5-MeO-DMT has been controlled in Turkey since December 2013.[87]

United States

5-MeO-DMT was made a Schedule I controlled substance in January 2011.[88]

Research

Preliminary clinical findings suggest that 5-MeO-DMT might have antidepressant and anxiolytic effects.[89][90]

A 2019 European study with 42 volunteers showed that a single inhalation of 5-MeO-DMT produced sustained enhancement of satisfaction with life, and easing of anxiety, depression, and post-traumatic stress disorder (PTSD).[60] A 2018 study found that a single dose of 5-MeO-DMT induced neurogenesis in mice.[91]

Depression

See also: Chemistry:List of investigational hallucinogens and entactogens

5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients with treatment-resistant depression (TRD).[92] Biopharmaceutical company GH Research has sponsored a completed phase 1 study in healthy volunteers[93] 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.[94][95] 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.[96]

In February 2025, GH Research announced that their Phase 2b clinical trial of GH001, met its primary endpoint in patients with TRD.[97] The trial demonstrated a placebo-adjusted reduction of 15.5 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) at day 8, with 57.7% of patients achieving remission compared to 0% in the placebo group.[97] The trial also met all secondary endpoints, and the treatment was well-tolerated with no serious adverse events reported.[97] In 2026, the FDA allowed advanced trials for GH001.[98]

Beckley Psytech in collaboration with King's College London evaluated the safety and tolerability of intranasal 5-MeO-DMT in healthy subjects, in a phase 1 study.[99][100] 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."[101] The research initiative by ataiBeckley, received a Breakthrough Therapy designation by the FDA for BPL-003, an intranasal spray containing 5-MeO-DMT, for Treatment-Resistant Depression.[98]

Ultra-short-acting psychedelics like dimethyltryptamine (DMT), bretisilocin 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.[102][103]

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.[9]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 "A narrative synthesis of research with 5-MeO-DMT". J Psychopharmacol 36 (3): 273–294. March 2022. doi:10.1177/02698811211050543. PMID 34666554. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 "The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)". J Neurochem 162 (1): 128–146. July 2022. doi:10.1111/jnc.15587. PMID 35149998. 
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 "5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk?". Psychopharmacology (Berl) 242 (7): 1457–1479. December 2023. doi:10.1007/s00213-023-06517-1. PMID 38072874. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Curr Drug Metab 11 (8): 659–666. October 2010. doi:10.2174/138920010794233495. PMID 20942780. 
  5. ↑ "The hallucinogenic world of tryptamines: an updated review". Archives of Toxicology 89 (8): 1151–1173. August 2015. doi:10.1007/s00204-015-1513-x. PMID 25877327. Bibcode: 2015ArTox..89.1151A. 
  6. ↑ "Ultimate Guide to 5-MeO-DMT - Experience, Benefits, & Side Effects". 29 June 2020. https://thethirdwave.co/psychedelics/5-meo-dmt/. 
  7. ↑ 7.0 7.1 "Other psychedelics". Psychedelics as Psychiatric Medications. Oxford University PressOxford. 2023. p. 95–C8P41. doi:10.1093/med/9780192863607.003.0008. ISBN 978-0-19-286360-7. "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 [...]" 
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 "Defining 5-MeO-DMT in Historical and Cultural Contexts". World Futures 80 (2): 174–197. 17 February 2024. doi:10.1080/02604027.2024.2330255. ISSN 0260-4027. https://www.researchgate.net/publication/379130421. "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.". 
  9. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 Hayes, Caroline (14 April 2025). "A Toad Less Traveled: Should 5-MeO-DMT Have a Role in Treating Depression?". Psychedelic Medicine. doi:10.1089/psymed.2024.0049. ISSN 2831-4425. https://www.liebertpub.com/doi/10.1089/psymed.2024.0049. Retrieved 6 May 2025. 
  10. ↑ 10.0 10.1 10.2 10.3 "Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile". Biol Psychiatry Cogn Neurosci Neuroimaging 9 (5): 472–489. May 2024. doi:10.1016/j.bpsc.2024.01.007. PMID 38301886. 
  11. ↑ "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics". Neuron 113 (19): 3129–3142.e9. October 2025. doi:10.1016/j.neuron.2025.06.012. PMID 40683247. https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/484fa5fe-79e2-4ff7-9dce-2944686fcfbc/mmc11.pdf. 
  12. ↑ 12.00 12.01 12.02 12.03 12.04 12.05 12.06 12.07 12.08 12.09 12.10 12.11 12.12 12.13 12.14 12.15 12.16 12.17 12.18 12.19 12.20 12.21 12.22 12.23 12.24 12.25 12.26 12.27 12.28 12.29 12.30 12.31 12.32 12.33 12.34 12.35 12.36 12.37 12.38 12.39 12.40 12.41 12.42 "Tryptamines I Have Known And Loved: The Continuation". 1997. https://erowid.org/library/books_online/tihkal/tihkal38.shtml. 
  13. ↑ 13.0 13.1 13.2 13.3 "Bufo alvarius: a potent hallucinogen of animal origin". J Ethnopharmacol 41 (1–2): 1–8. January 1994. doi:10.1016/0378-8741(94)90051-5. PMID 8170151. https://www.reptilis.org/pdf/Amphibiens/Bufo%20alvarius-%20a%20potent%20hallucinogen%20of%20animal%20origin.pdf. 
  14. ↑ "Toxicology and Analysis of Psychoactive Tryptamines". Int J Mol Sci 21 (23): 9279. December 2020. doi:10.3390/ijms21239279. PMID 33291798. 
  15. ↑ "Population Survey Data Informing the Therapeutic Potential of Classic and Novel Phenethylamine, Tryptamine, and Lysergamide Psychedelics". Front Psychiatry 10. 2019. doi:10.3389/fpsyt.2019.00896. PMID 32116806. 
  16. ↑ "A Toad Less Traveled: Should 5-MeO-DMT Have a Role in Treating Depression?". Psychedelic Medicine. 14 April 2025. doi:10.1089/psymed.2024.0049. ISSN 2831-4425. https://www.liebertpub.com/doi/10.1089/psymed.2024.0049. Retrieved 6 May 2025. 
  17. ↑ 17.0 17.1 17.2 "Erowid Online Books: "TIHKAL" - #13 HARMALINE". http://www.erowid.org/library/books_online/tihkal/tihkal13.shtml. 
  18. ↑ 18.0 18.1 "Bufo alvarius: The Psychedelic Toad of the Sonoran Desert". 1984. https://www.erowid.org/archive/sonoran_desert_toad/almost.htm. 
  19. ↑ Morris H (28 November 2017). "The Psychedelic Toad". Hamilton's Pharmacopeia. Season 2. Episode 1. Vice Media. Viceland.
  20. ↑ Morris H (4 January 2021). "Synthetic Toad Venom Machine". Hamilton's Pharmacopeia. Season 3. Episode 1. Vice Media. Viceland.
  21. ↑ "Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences". Sci Adv 8 (11). March 2022. doi:10.1126/sciadv.abl6989. PMID 35294242. 
  22. ↑ 22.0 22.1 "Mapping the phenomenology of intranasal 5-MeO-DMT in psychedelic-naïve healthy adults". Sci Rep 15 (1): 38874. November 2025. doi:10.1038/s41598-025-22620-z. PMID 41198731. 
  23. ↑ 23.0 23.1 23.2 23.3 23.4 Thomas, Kelan (2024). Toxicology and Pharmacological Interactions of Classic Psychedelics. Current Topics in Behavioral Neurosciences. Berlin, Heidelberg: Springer Berlin Heidelberg. doi:10.1007/7854_2024_508. https://link.springer.com/10.1007/7854_2024_508. Retrieved 14 May 2025. 
  24. ↑ 24.0 24.1 "A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation". J Anal Toxicol 29 (8): 838–841. 2005. doi:10.1093/jat/29.8.838. PMID 16356341. 
  25. ↑ 25.0 25.1 "Psychedelics and the human receptorome". PLOS ONE 5 (2). February 2010. doi:10.1371/journal.pone.0009019. PMID 20126400. Bibcode: 2010PLoSO...5.9019R. 
  26. ↑ 26.0 26.1 26.2 26.3 "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature 589 (7842): 474–479. January 2021. doi:10.1038/s41586-020-3008-z. PMID 33299186. Bibcode: 2021Natur.589..474C. 
  27. ↑ 27.0 27.1 "Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor". Psychopharmacology (Berl) 221 (4): 709–718. June 2012. doi:10.1007/s00213-011-2616-6. PMID 22222861. 
  28. ↑ 28.0 28.1 "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. June 2015. doi:10.1021/acs.jmedchem.5b00245. PMID 26023814. 
  29. ↑ 29.00 29.01 29.02 29.03 29.04 29.05 29.06 29.07 29.08 29.09 29.10 29.11 "Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes". Psychopharmacology (Berl) 231 (21): 4135–4144. October 2014. doi:10.1007/s00213-014-3557-7. PMID 24800892. 
  30. ↑ 30.0 30.1 "Evaluation of the Indazole Analogs of 5-MeO-DMT and Related Tryptamines as Serotonin Receptor 2 Agonists". ACS Med Chem Lett 15 (2): 302–309. February 2024. doi:10.1021/acsmedchemlett.3c00566. PMID 38352850. 
  31. ↑ Andrew Carry Kruegel, "Methods of treating mood disorders", US patent 11440879, published 10 February 2022, assigned to Gilgamesh Pharmaceuticals, Inc.
  32. ↑ "A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines". J Biol Chem 299 (10). October 2023. doi:10.1016/j.jbc.2023.105231. PMID 37690691. 
  33. ↑ Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery, 10 March 2023, doi:10.21203/rs.3.rs-2667175/v1, https://www.researchsquare.com/article/rs-2667175/latest.pdf, retrieved 18 March 2025 
  34. ↑ 34.0 34.1 34.2 "PDSP Database" (in zu). https://pdsp.unc.edu/databases/pdsp.php?testDDRadio=testDDRadio&testLigandDD=1287&kiAllRadio=all&doQuery=Submit+Query. 
  35. ↑ 35.0 35.1 35.2 35.3 "BindingDB BDBM30707 2-(5-methoxy-1H-indol-3-yl)-N,N-dimethyl-ethanamine::2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine::2-(5-methoxy-1H-indol-3-yl)ethyl-dimethyl-amine::3-(2-DIMETHYLAMINOETHYL)-5-METHOXYINDOLE::CHEMBL7257::MLS000069438::Methoxydimethyltryptamines::SMR000059066::US20240166618, Compound 5-MeO-DMT::WO2023019367, Compound 5-MeO-DMT::cid_1832". https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=30707. 
  36. ↑ 36.0 36.1 "Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties". Molecular Psychiatry 29 (8): 2346–2358. August 2024. doi:10.1038/s41380-024-02506-8. PMID 38486047. 
  37. ↑ "Serotonin autoreceptors on dorsal raphe neurons: structure-activity relationships of tryptamine analogs". J Neurosci 1 (10): 1148–1154. October 1981. doi:10.1523/JNEUROSCI.01-10-01148.1981. PMID 6793698. 
  38. ↑ "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. December 2006. doi:10.1007/s00213-006-0566-1. PMID 17013638. 
  39. ↑ "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology 559 (2–3): 132–137. March 2007. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101. 
  40. ↑ "Serotonin 5-HT2C Receptor Signaling Analysis Reveals Psychedelic Biased Agonism". ACS Chem Neurosci 16 (19): 3899–3914. October 2025. doi:10.1021/acschemneuro.5c00647. PMID 40944639. 
  41. ↑ 41.0 41.1 41.2 "Pharmacological characterisation of psilocybin and 5-MeO-DMT discriminative cues in the rat and their translational value for identifying novel psychedelics". J Psychopharmacol. August 2025. doi:10.1177/02698811251361453. PMID 40862395. "However, in line with previous investigations, the dominant receptor subtypes mediating the psilocybin and 5-MeO-DMT cues were the 5-HT2A and 5-HT1A receptor subtypes, respectively (Halberstadt, 2015; Nichols, 2016; Winter et al., 2007; Winter, 2009). Probably by virtue of their subtype selectivity, the clearest evidence emerged from the antagonist experiments. Thus, the 5-MeO-DMT cue was almost completely blocked (~80%) by the selective 5-HT1A antagonist WAY100635, a finding consistent with prior studies (Spencer et al., 1987; Winter et al., 2000). Of the other antagonists tested, the only minor change was a subtle reduction (~20%) produced by M100907 pre-treatment, suggestive of a minor 5-HT2A receptor component to this cue. 5-HT1B, 5-HT2B and 5-HT2C receptor selective antagonists, each tested at pharmacologically relevant dose regimens (see Table 1 references), had no effect on the cueing effects of 5-MeO-DMT. [...] An interesting finding, and consistent with previous research (Schreiber and de Vry, 1993; Spencer et al., 1987; Winter et al., 2000), is that despite a prominent agonist property at both 5-HT1A and 5-HT2A receptors (Ermakova et al., 2022; Warren et al., 2024), the cueing properties of 5-MeO-DMT appear to be principally driven via interaction at the 5-HT1A receptor. Given the profile of 5-MeO-DMT across 5-HT receptor subtypes as measured by in vitro cell-based screens (Ermakova et al., 2022; Holze et al., 2024; Warren et al., 2024), it is highly likely that at the 1 mg/kg training dose, multiple 5-HT receptor subtypes are engaged. Indeed, 5-MeO-DMT fully generalised to the psilocybin cue at 0.6–1mg/kg, supporting a 5-HT2A receptor interaction across this dose range. While the 1mg/kg training dose of 5-MeO-DMT likely exerts stimulus control via a compound stimulus, the 5-HT1A receptor clearly represents the dominant component. This is supported both by the generalisation profiles of 8-OH DPAT and lisuride, each of which have high 5-HT1A agonist property (Marona-Lewicka et al., 2002; Schreiber and de Vry, 1993; Spencer et al., 1987; Tricklebank et al., 1987), and secondly by an approximate 80% cue block by the selective 5-HT1A antagonist WAY100635 (Fletcher et al., 1996; see also Winter et al., 2000).". 
  42. ↑ 42.0 42.1 42.2 42.3 42.4 "Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans". Molecules 26 (9): 2451. April 2021. doi:10.3390/molecules26092451. PMID 33922330. 
  43. ↑ "Recent advances in the neuropsychopharmacology of serotonergic hallucinogens". Behav Brain Res 277: 99–120. January 2015. doi:10.1016/j.bbr.2014.07.016. PMID 25036425. 
  44. ↑ 44.0 44.1 "Significance of mammalian N, N-dimethyltryptamine (DMT): A 60-year-old debate". J Psychopharmacol 36 (8): 905–919. August 2022. doi:10.1177/02698811221104054. PMID 35695604. 
  45. ↑ "The mechanistic divide in psychedelic neuroscience: An unbridgeable gap?". Neurotherapeutics 21 (2). March 2024. doi:10.1016/j.neurot.2024.e00322. PMID 38278658. 
  46. ↑ "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nat Commun 14 (1). December 2023. doi:10.1038/s41467-023-44016-1. PMID 38102107. Bibcode: 2023NatCo..14.8221W. 
  47. ↑ "Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents". Biomedicines 11 (2): 461. February 2023. doi:10.3390/biomedicines11020461. PMID 36830997. 
  48. ↑ 48.0 48.1 "Bufotenine: toward an understanding of possible psychoactive mechanisms". J Psychoactive Drugs 32 (3): 321–331. 2000. doi:10.1080/02791072.2000.10400456. PMID 11061684. 
  49. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named BistueMillónNogueraBruno2025
  50. ↑ "We Licked the Toads so You Don't Have to: A Comprehensive Analysis of the Chemical Syntheses of the Classical Psychedelics Bufotenin(e) and 5-Methoxy-N,N-Dimethyltryptamine". ChemMedChem 21 (4). February 2026. doi:10.1002/cmdc.202500525. PMID 41765690. 
  51. ↑ "Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use". ACS Omega 5 (49): 32067–32075. December 2020. doi:10.1021/acsomega.0c05099. PMID 33344861. 
  52. ↑ "Psychedelic Toads Pushed To The Limit, Conservationists Urge Synthetic 5-MeO-DMT Option" (in en). 2021-02-02. https://www.forbes.com/sites/davidcarpenter/2021/02/02/psychedelic-toads-pushed-to-the-limit-conservationists-urge-synthetic-5-meo-dmt-option/. 
  53. ↑ "Effect of Hallucinogens on Unconditioned Behavior". Curr Top Behav Neurosci 36: 159–199. 2018. doi:10.1007/7854_2016_466. PMID 28224459. "Further work demonstrated that α,α,β,β-tetradeutero-5-MeO-DMT, a 5-MeO-DMT isotopologue that is resistant to metabolism by MAO, does not require an MAOI to produce a biphasic locomotor profile (Halberstadt et al. 2012). The latter finding indicates that MAOIs alter the behavioral profile of 5-MeO-DMT by slowing its biotransformation, which allows high levels of the drug to accumulate in the brain. Indeed, we found that the concentration of 5-MeO-DMT in the CNS is increased ~20-fold in animals pretreated with an MAOI (Halberstadt 2016).". 
  54. ↑ "Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment". Psychopharmacology 237 (3): 773–785. March 2020. doi:10.1007/s00213-019-05414-w. PMID 31822925. 
  55. ↑ 55.0 55.1 55.2 55.3 55.4 55.5 55.6 55.7 55.8 "tryptamines: fungi". http://bluezoo.org/tryptamines/plants.html. 
  56. ↑ 56.0 56.1 56.2 56.3 56.4 "Erowid Psychoactive Vaults: Tryptamine FAQ". https://www.erowid.org/psychoactives/faqs/faqs_tryptamine.shtml. 
  57. ↑ 57.0 57.1 57.2 57.3 57.4 57.5 57.6 "Some simple tryptomines". https://troutsnotes.com/pdf/SomeSimpleTryptamines_2ndEd_2007_with_addendum.pdf. 
  58. ↑ 58.0 58.1 58.2 58.3 58.4 58.5 58.6 58.7 58.8 Basic Principles of Forensic Chemistry. Springer Science & Business Media. 2011. p. 195. ISBN 978-1-934115-06-0. https://books.google.com/books?id=9qrXBjRF388C&pg=PA195. 
  59. ↑ "5-MeO-DMT: The 20-Minute Psychoactive Toad Experience That's Transforming Lives". https://www.forbes.com/sites/davidcarpenter/2020/02/02/5-meo-dmt-the-20-minute-psychoactive-toad-experience-thats-transforming-lives/. 
  60. ↑ 60.0 60.1 "A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms". Psychopharmacology 236 (9): 2653–2666. September 2019. doi:10.1007/s00213-019-05236-w. PMID 30982127. 
  61. ↑ "Demand for This Toad's Psychedelic Toxin Is Booming. Some Warn That's Bad for the Toad." (in en-US). The New York Times. 2022-03-20. ISSN 0362-4331. https://www.nytimes.com/2022/03/20/us/toad-venom-psychedelic.html. 
  62. ↑ "The Sonoran Desert toad can get you high. Poachers have taken notice." (in en). 2023-07-12. https://www.nationalgeographic.com/animals/article/sonoran-desert-toad-dmt-psychedelic-movement. 
  63. ↑ "Preface". Bufo alvarius: The Psychedelic Toad of the Sonoran Desert (2021 ed.). 2021-02-02. https://www.psychedelictoadofthesonorandesert.com/preface. Retrieved 2023-10-20. 
  64. ↑ "Über die synthese des bufotenin-methyl-äthers (5-methoxy-n-dimethyl-tryptamin) und bufotenins (synthesen in der indol-gruppe. XV)". Bulletin of the Chemical Society of Japan 11 (3): 221–224. 1 March 1936. doi:10.1246/bcsj.11.221. ISSN 0009-2673. 
  65. ↑ "Indole Alkaloids of Acer saccharinum (the Silver Maple), Dictyoloma incanescens, Piptadenia colubrina, and Mimosa hostilis". The Journal of Organic Chemistry 24 (9): 1285–1287. 1959. doi:10.1021/jo01091a032. ISSN 0022-3263. 
  66. ↑ 66.0 66.1 66.2 "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. 1975. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. https://bitnest.netfirms.com/external/Books/978-0-85608-011-1. 
  67. ↑ 67.0 67.1 "Structure-activity relationships among 5-methoxy-n:n-dimethyltryptamine, 4-hydroxy-n:n-dimethyltryptamine (psilocin) and other substituted tryptamines". Life Sci 7 (5): 267–277. March 1968. doi:10.1016/0024-3205(68)90200-2. PMID 5641719. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=b45d79b71663e4451de894d16a1c868141dfeaaf. 
  68. ↑ "Pharmacological actions of some methoxyindolealkylamines". Nature 190 (4771): 179–180. April 1961. doi:10.1038/190179a0. PMID 13704827. Bibcode: 1961Natur.190..179G. 
  69. ↑ "Behavioral effects of 5-methoxy-N:N-dimethyltryptamine, other tryptamines, and LSD". American Journal of Physiology. Legacy Content 203 (1): 167–172. 1 July 1962. doi:10.1152/ajplegacy.1962.203.1.167. ISSN 0002-9513. 
  70. ↑ "Toxicity of Phalaris tuberosa for Sheep". Nature 204 (4958): 542–545. November 1964. doi:10.1038/204542a0. PMID 14238156. Bibcode: 1964Natur.204..542G. 
  71. ↑ 71.0 71.1 "Psychotomimetic Agents". Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. 4. Academic Press. 1976. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. https://bitnest.netfirms.com/external/10.1016/B978-0-12-290559-9.50011-9. 
  72. ↑ "Tryptamine derivatives in Epená, an intoxicating snuff used by some South American Indian tribes". Arch Int Pharmacodyn Ther 156 (2): 285–305. August 1965. PMID 5868939. 
  73. ↑ "5-Methoxy- and 5-hydroxy-indolealkylamines in the skin of Bufo alvarius". Experientia 21 (9): 504. September 1965. doi:10.1007/BF02138956. PMID 5872604. https://link.springer.com/content/pdf/10.1007/BF02138956.pdf. 
  74. ↑ "5-Methoxy- and 5-hydroxyindoles in the skin of Bufo alvarius". Biochem Pharmacol 16 (7): 1149–1164. July 1967. doi:10.1016/0006-2952(67)90147-5. PMID 6053590. https://core.ac.uk/download/pdf/286811965.pdf. 
  75. ↑ Alexander Shulgin (1970). "Chemistry and Structure-Activity Relationships of the Psychotomimetics". in D. H. Efron. Psychotomimetic Drugs. New York: Raven Press. pp. 21–41. https://www.erowid.org/library/books_online/psychotomimetic_drugs.pdf#page=23. 
  76. ↑ 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."
  77. ↑ "A multidisciplinary overview of intoxicating enema rituals in the western hemisphere". J Ethnopharmacol 9 (2–3): 129–166. December 1983. doi:10.1016/0378-8741(83)90031-4. PMID 6677814. "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".". 
  78. ↑ "Identity of a New World Psychoactive Toad". Ancient Mesoamerica 3 (1): 51–59. 1992. doi:10.1017/S0956536100002297. ISSN 0956-5361. 
  79. ↑ "Misuse and legend in the "toad licking" phenomenon". Int J Addict 28 (6): 521–538. May 1993. doi:10.3109/10826089309039645. PMID 8486435. 
  80. ↑ "back cover". The Book of Sacraments: Ritual Use of Magical Plants. Ronin Publishing. 2015. ISBN 978-1-57951-210-1. 
  81. ↑ 81.0 81.1 "5-MeO-DMT Timeline". Erowid. https://www.erowid.org/chemicals/5meo_dmt/5meo_dmt_timeline.php. 
  82. ↑ "Poisons Standard July 2016". Federal Register of Legislation. 24 June 2016. https://www.legislation.gov.au/Details/F2016L01071. 
  83. ↑ "Controlled Drugs and Substances Act". 5 December 2025. https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  84. ↑ "Is 5-MeO-DMT (Bufo) Legal in Canada? Understanding 5-MeO-DMT Laws and Regulations" (in en-US). https://www.psychedeliclaw.ca/5meodmt-bufotenin. 
  85. ↑ "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. http://www.sfda.gov.cn/WS01/CL0056/130753.html. 
  86. ↑ "Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor" (in sv). Svensk författningssamling. 7 September 2004. https://www.notisum.se/rnp/sls/sfs/20040696.pdf. 
  87. ↑ "Turkish Law". Resmi Gazete. 16 December 2013. http://www.resmigazete.gov.tr/eskiler/2014/01/20140125-3-1.pdf. 
  88. ↑ Drug Enforcement Administration (DEA), Department of Justice (December 2010). "Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule". Federal Register 75 (243): 79296–79300. PMID 21171485. https://www.gpo.gov/fdsys/pkg/FR-2010-12-20/pdf/2010-31854.pdf. 
  89. ↑ "5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety". The American Journal of Drug and Alcohol Abuse 45 (2): 161–169. March 2019. doi:10.1080/00952990.2018.1545024. PMID 30822141. 
  90. ↑ "The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption". Journal of Psychopharmacology 32 (7): 779–792. July 2018. doi:10.1177/0269881118769063. PMID 29708042. 
  91. ↑ "A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus". Frontiers in Molecular Neuroscience 11. 2018. doi:10.3389/fnmol.2018.00312. PMID 30233313. 
  92. ↑ "Home | GH Research". https://www.ghres.com/. 
  93. ↑ "A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers". Frontiers in Pharmacology 12. 2021. doi:10.3389/fphar.2021.760671. PMID 34912222. 
  94. ↑ "A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression". Front Psychiatry 14. 2023. doi:10.3389/fpsyt.2023.1133414. PMID 37409159. 
  95. ↑ GH Research PLC (2021-12-06). "GH Research Announces Successful Outcome of the Phase 2 part of its Phase 1/2 Clinical Trial of GH001 in Treatment-Resistant Depression". GlobeNewswire News Room (Press release). Retrieved 2022-10-07.
  96. ↑ GH Research PLC (2022-08-23). "GH Research Reports Second Quarter 2022 Financial Results and Provides Business Updates". GlobeNewswire News Room (Press release). Retrieved 2022-10-07.
  97. ↑ 97.0 97.1 97.2 "GH Research Announces Primary Endpoint Met in Phase 2b Trial with GH001 in TRD Demonstrating -15.5 Point Placebo-adjusted MADRS Reduction". February 3, 2025. https://investor.ghres.com/news-releases/news-release-details/gh-research-announces-primary-endpoint-met-phase-2b-trial-gh001. 
  98. ↑ 98.0 98.1 Kasoff, Josh (2026-03-16). "Federal Support for U.S. Psychedelic Research Accelerates 5-MeO-DMT Clinical Trials" (in en-US). https://www.lucid.news/federal-support-for-u-s-psychedelic-research-accelerates-5-meo-dmt-clinical-trials/,%20https://www.lucid.news/federal-support-for-u-s-psychedelic-research-accelerates-5-meo-dmt-clinical-trials/. 
  99. ↑ "More Companies Embrace 5-MeO-DMT to Create Therapies" (in en-US). 2022-02-16. https://www.lucid.news/companies-embrace-5-meo-dmt-therapies/. 
  100. ↑ Atai Life Sciences (2024-03-27). "atai Life Sciences Announces Positive Initial Results from Beckley Psytech's Phase 2a Open Label Study of BPL-003 (Intranasal 5-MeO-DMT) in Treatment Resistant Depression". GlobeNewswire News Room (Press release). Retrieved 2024-10-06.
  101. ↑ "Could 5-MeO-DMT Allow For More Affordable Psychedelic-Assisted Therapy? Beckley Psytech Thinks So" (in en). https://www.forbes.com/sites/amandasiebert/2022/02/28/could-5-meo-dmt-allow-for-more-affordable-psychedelic-assisted-therapy--beckley-psytech-thinks-so/. 
  102. ↑ "Less is more? Antidepressant effects of short-acting psychedelics". Neuropsychopharmacology 50 (6): 875–876. May 2025. doi:10.1038/s41386-025-02103-5. PMID 40258989. 
  103. ↑ "Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression". The American Journal of Psychiatry 182 (1): 33–46. January 2025. doi:10.1176/appi.ajp.20230890. PMID 39741439. https://cris.maastrichtuniversity.nl/en/publications/fb3d3cba-472c-42bf-b665-bf9607461199. 



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